b = 3-23
What does the thymus do?
(central) release T cells
cytokine functions
- guide immune cell migration - activate intracellular signaling - activate innate immune cells - activate adaptive immune cells
Which of the following statements about pattern-recognition receptors on innate immune cells is/are true? 1. pattern-recognition receptors trigger cells to coordinate killing of pathogens. 2. pattern-recognition receptors trigger cells to alert the adaptive immune system of an infection. 3. pattern-recognition receptors each recognize a specific pathogen 4. pattern-recognition receptors are only expressed on APCs
1 and 2 only
List at least three mechanisms/factors by which microbes are killed by components of innate immunity.
1) Acidic pH and antimicrobial proteins and peptides on the physical layers of the epithelial linings. 2) Phagocytosis through dendritic cells 3) Killing through natural killer cells
Time Period of Innate Immune Response
1-4 days
Time Period of Adaptive Immune response
1-4 weeks
Name 2 immediate defensive mechanisms of innate immune system?
1. Antimicrobial enzymes such as lysozyme begin to digest bacterial cell walls. 2. ANTIMICROBIAL PEPTIDES such as DEFENSINS breakdown bacterial cell membranes directly. 3. The COMPLEMENT SYSTEM that targets pathogens both for lysis and for phagocytosis by cells of the innate immune system such as MACROPHAGES Remember that these soluble molecules are present in extracellular fluid, blood, and epithelial secretions . They can either kill the pathogen or weaken its effect.
Two types of antimicrobial agents
1. Antimicrobial proteins: Such as Lysozyme and Secretory Phospholipase A 2. Antimicrobial Peptides: Such as Defensins, Cathelicidins and Histatins
What is Lysozyme and how does it work?
1. Lysozyme is an enzyme that attacks the chemical features specific to bacterial cell wall. 2. Specifically, Lysozyme is a glycosidase that breaks a specific chemical bond in the peptidoglycan component of the bacterial cell wall.
what are the 3 Surface defenses of the immune system
1. Mechanical barriers: such as Epithelial Cell Layers and Mucus 2. Clearing Mechanisms: Such as cila function, coughing, tears, sneezing, peristalsis. ( wave like muscle contractions tha moves stuff) 3. Microbiome: Normal flora that competes with pathogens for nutrients and binding sites
Name 2 protective functions of mucus?
1. Microorganisms coated in mucus may be prevented from adhering to the epithelium. 2. In the respiratory tract, microorganisms can be expelled in the outward flow of mucus driven by the beating of cilia on the mucosal epithelium 3.
alpha:beta TCRs are membrane-bound proteins comprised of two polypeptides linked by a disulfide bond. Both polypeptide components of the alpha:beta TCR are members of the immunoglobulin superfamily, and each of their domains share structural similarity with regions of antibody proteins. However, due to the different functions of TCRs versus antibodies, the overall domain organization of the TCR is not the same as for an antibody. In the cartoon in Figure Q4.14, describe three features that are incorrect illustrations of the alpha:beta TCR.
1. alpha:beta TCRs have only one V and one C region domain per polypeptide. 2. alpha:beta TCRs have a disulfide bond at the C-terminal side of the single Calpha and Cbeta domains, just amino-terminal to the transmembrane region. 3. alpha:beta TCRs have only one binding site for antigen 4. The antigen-binding site of the alpha:beta TCR is comprised of both the Valpha and Vbeta domains together.
What are the 2 types of antimicrobial agents?
1. antimicrobial enzymes 2. antimicrobial peptides
The basic immunoglobulin (Ig) unit is composed of
2 identical heavy chains and 2 identical light chains
The indicated items are found in the gene for an Ig light chain gene. The sequence of which of the labeled element/elements are absolutely conserved
7 bp and 9 bp
Peptides are geneally _____amino acids in length
8-10
In Figure Q4.8, which close-up view of these two V domains has the amino acid sequences most important for antigen-binding highlighted correctly in red?
A
Secondary (or peripheral) lymphoid organs are sites for initiation of adaptive immune responses. Given the rarity of lymphocytes specific for any given antigen and the vast amount of body tissue that must be protected, the system of secondary lymphoid tissues is efficient because: A. It concentrates antigens in centralized locations for rare lymphocytes to encounter B. It provides the optimal environment for the rapid proliferation of lymphocytes C. It traps the pathogens and antigens in a contained environment so they cannot spread to other tissues in the body D. It helps the innate immune cells eliminate the infection by using lymphatic fluid to drain pathogens from the infected tissue E. It filters the lymph fluid and removes pathogenic organisms before they can enter the bloodstream
A
Vaccination against many infectious diseases has provided enormous benefit in developed countries, leading to the virtual eradication of diseases such as polio, measles, smallpox, and others. However, efforts to create long-lasting vaccines against some viral infections, like Influenza and HIV, have not been successful to date because: A. Viruses like HIV and Influenza undergo antigenic variation to evade previous immune responses. B. Viruses like HIV and Influenza spread too rapidly in the population for a vaccine to be effective. C. Viruses like HIV and Influenza have RNA, rather than DNA genomes, and are resistant to current vaccine strategies. D. Viruses like HIV and Influenza infect via mucosal surfaces, a route that is not well protected by current vaccine strategies. E. Viruses like HIV and Influenza are transmitted vertically (from mother to child) during fetal development, so babies are infected before they can be vaccinated.
A
When stimulated by binding to bacterial products, the fMet-Leu-Phe (fMLF) receptor triggers multiple responses by phagocytes, including migration and induction of antimicrobial activities. Most of these responses are activated by small GTPases of the Rac and Rho families that are indirectly activated by fMLF receptor stimulation. The fMLF receptor can initiate multiple downstream signaling pathways because: A. It couples to a heterotrimeric G protein that has and subunits with independent activities. B. It couples directly to two different guanine nucleotide exchange factors (GEFs). C. It binds to Rac, Rho, and cdc42 directly. D. It promotes fusion of phagosomes with lysosomes, initiating multiple signals. E. It induces assembly of multiple enzymes from individual cytosolic components.
A
Early studies analyzing the antibody protein fragments generated after proteolytic cleavage revealed important information about the overall structure of the antibody molecule. Which cleavage pattern (indicated by the red triangles in Figure Q4.5) yields a fragment that has the same antigen-binding avidity as the intact antibody, but is unable to activate complement after binding to a pathogen?
A 4.5
n mice that lack both MHC class I and class II in the thymus, T cell development will show:
A block in T cell development at the CD4+CD8+ double-positive stage
CXCR5 is the receptor for the chemokine CXCL13, secreted by follicular stromal cells and follicular dendritic cells in the B cell zones (i.e., lymphoid follicles) of secondary lymphoid organs. A conditional knockout mouse in which CXCR5 was specifically deleted only in T cells would have ___
A defect in T cell-dependent antibody responses
In an MLR, the uptake of 3H-thymidine is often used to assess cell proliferation. A) Which cell type (responders or stimulators) proliferates in an MLR? Why? B) Explain why IL-2 production can also be used to assess cell proliferation in an MLR.
A) T cells (CD4+ and CD8+) as long as both MHC class I and class II differ. B) To demonstrate the identity of the proliferating cells, you could incubate them with distinct fluorochrome conjugated antibodies (e.g., fluorescein-labeled anti-CD4 monoclonal antibody and phycoerythrin-labeled anti-CD8 monoclonal antibody). The proliferating cells will be stained only with the anti-CD4 reagent.
1.6 Multiple choice: Adaptive immune responses are slow to develop, taking days to weeks after exposure to reach their peak. However, these responses are more specific than innate responses, and also generate immunological memory. These latter features, which provide enhanced protection upon re-infection with the same pathogen, are the basis of: A. Vaccines B. Antibiotics C. Systemic shock D. Complement activation E. Phagocytosis
A. Vaccines are designed to generate an adaptive immune response to a non-disease-causing form of a pathogen, or a pathogen product. Due to the specificity of this response, and the generation of immunological memory, vaccinated individuals make a substantially more robust response, and are often completed protected from infection, when exposed to the pathogen at a later time.
In Figure Q4.8, which close-up view of these two V domains has the amino acid sequences most important for antigen-binding highlighted correctly in red?
A. (All 6 loops are in red)
Opsonization of pathogens by both antibodies and complement proteins (C3b) leads to uptake and destruction of the pathogen by phagocytic cells that express both Fc receptors and complement receptors. Which of the following in Figure Q2.16 is the most efficient form of dual opsonization of the pathogen by antibody and C3b to maximize phagocytosis?
A. (Pathogen, antibody, and C3b are all labeled)
Multiple choice: When macrophages in a tissue encounter bacteria, they release cytokines that induce an inflammatory response. These cytokines act on other immune cells, to recruit them to the site of infection and to enhance their activities. In addition, these cytokines act on the endothelial cells of the blood vessel wall to: A. Increase their permeability, allowing fluid and proteins to leak into the tissue B. Solidify the tight junctions to prevent the bacteria from entering the blood C. Proliferate, allowing the blood vessel to enlarge D. Up-regulate microbicidal mechanisms, so they can kill bacteria E. Secrete anti-microbial peptides
A. Increase their permeability, allowing fluid and proteins to leak into the tissue
Multiple choice: Secondary (or peripheral) lymphoid organs are sites for initiation of adaptive immune responses. Given the rarity of lymphocytes specific for any given antigen and the vast amount of body tissue that must be protected, the system of secondary lymphoid tissues is efficient because: A. It concentrates antigens in centralized locations for rare lymphocytes to encounter B. It provides the optimal environment for the rapid proliferation of lymphocytes C. It traps the pathogens and antigens in a contained environment so they cannot spread to other tissues in the body D. It helps the innate immune cells eliminate the infection by using lymphatic fluid to drain pathogens from the infected tissue E. It filters the lymph fluid and removes pathogenic organisms before they can enter the bloodstream
A. It concentrates antigens in centralized locations for rare lymphocytes to encounter
Multiple choice: Opsonization of pathogens by both antibodies and complement proteins (C3b) leads to uptake and destruction of the pathogen by phagocytic cells that express both Fc receptors and complement receptors. Which of the following in Figure Q2.16 is the most efficient form of dual opsonization of the pathogen by antibody and C3b to maximize phagocytosis? (LOOK AT PICTURE)
A. Look at picture (one with words)
Multiple choice: Peptide editing is an important component of antigen presentation for both MHC class I and MHC class II pathways, as it drives the preferential presentation of high-affinity binding peptides. For MHC class II peptide editing, HLA-DM plays a key role. In the absence of HLA-DM: A. MHC class II molecules traffic to the cell surface with CLIP in their binding sites. B. No MHC class II molecules are released to traffic to the cell surface. C. MHC class II molecules bind to HLA-DO and are inhibited from binding peptides. D. Pathogens can evade the immune system by blocking peptide exchange on MHC class II. E. HLA-DO competes for high-affinity binding peptides with MHC class II molecules and blocks antigen presentation.
A. MHC class II molecules traffic to the cell surface with CLIP in their binding sites.
Multiple choice: NK cells can be activated following recognition of a virus-infected cell, if that cell has down-regulated expression of MHC class I proteins on its surface. However, NK cells can also recognize infected cells or tumor cells, even if they still express MHC class I proteins. In this latter case, activating receptors on NK cells are recognizing: A. Molecules on the target cell up-regulated by cellular or metabolic stress B. Cytokines secreted by the virus-infected or tumor cell C. MHC class I-like decoy molecules encoded by the virus D. Mutated self-proteins expressed by the tumor cell E. Double-stranded DNA in the cytoplasm of the infected or tumor cell
A. Molecules on the target cell up-regulated by cellular or metabolic stress
Multiple choice: Some pathogenic microorganisms encode proteins, such as the Staphylococcus Protein A, that bind to immunoglobulin constant region domains with high affinity. These microbial proteins provide a benefit to the microorganism by: A. Preventing antibodies bound to the microbe from binding to Fc receptors on phagocytes B. Blocking the binding of anti-microbial antibodies to the pathogen surface C. Cleaving the antibody into fragments that separate the antigen-binding region from the effector function D. Inducing aggregation of the anti-microbial antibodies by multivalent binding to the pathogen-derived protein E. Preventing the antibody from neutralizing the pathogen
A. Preventing antibodies bound to the microbe from binding to Fc receptors on phagocytes
Multiple choice: Septic shock is a serious, often fatal response to an infection in the bloodstream. This response can be elicited in mice by intravenous injection of bacterial LPS. However, it was found that one strain of mice, C3H/HeJ, is resistant to LPS-induced shock. This fact was used to clone the gene for TLR-4 based on positional cloning from C3H/HeJ mice. Another example of a strain of mice that is resistant to LPS-induced septic shock is: A. TNF-receptor-deficient mice B. TLR-2-deficient mice. C. LFA-1-deficient mice D. Neutrophil-deficient mice E. Complement receptor-deficient mice
A. TNF-receptor-deficient mice
Second messengers, such as calcium ions (Ca2+), are chemical mediators commonly used in intracellular signaling pathways. Despite its common usage in many different cell types in the body, Ca2+ has specific effects in lymphocytes following antigen receptor stimulation. The specific responses of lymphocytes to increased concentrations of intracellular Ca2+ are determined by: A. The expression of a specific subset of Ca2+-responsive enzymes in lymphocytes compared to other cell types B. The increased expression of calmodulin in lymphocytes compared to other cell types C. The presence of enzymes that bind calmodulin in lymphocytes but not other cell types D. The high levels of Ca2+ in the endoplasmic reticulum of lymphocytes compared to other cell types E. The ability of Ca2+ to amplify signaling pathways in lymphocytes but not other cell types
A. The expression of a specific subset of Ca2+ responsive enzymes in lymphocytes compared to other cell types.
Multiple choice: One surprising aspect of the immune system is that individuals make responses to human tissues from a different individual, causing serious problems for organ and tissue transplantation. The basis for this immune response is: A. The extensive polymorphism of MHC genes in the human population B. The fact that transplanted tissues often carry infectious microbes into the recipient C. The fact that individuals may differ in their blood group antigens (i.e., their blood type) D. The presence of many antigen-presenting-cells in the transplanted tissue E. The presence of many B and T lymphocytes in the transplanted tissue
A. The extensive polymorphism of MHC genes in the human population
In the absence of an infection, most granulocytes (neutrophils, eosinophils, basophils) are found circulating in the blood, whereas other subsets of myeloid cells reside in tissues. A. True B. False
A. True
One factor that contributes to the enhanced secondary response to an antigen is the increased number of antigen-specific lymphocytes present after the primary response; these are known as memory cells. A. True B. False
A. True
Multiple choice: Although the complement cascade can be initiated by antibodies bound to the surface of a pathogen, complement activation is generally considered to be an innate immune response. This is because: A. Two of the three pathways for complement activation are initiated by constitutively produced recognition molecules that directly interact with microbial surfaces. B. When the complement cascade leads to the formation of a membrane-attack complex, the pathogen is killed. C. Several of the soluble products generated by complement activation lead promote the inflammatory response. D. Complement proteins bound to the pathogen promote uptake and destruction by phagocytic cells. E. The C3 convertase is only produced when complement activation is initiated by antibody binding to a pathogen.
A. Two of the three pathways for complement activation are initiated by constitutively produced recognition molecules that directly interact with microbial surfaces.
Adaptive immune responses are slow to develop, taking days to weeks after exposure to reach their peak. However, these responses are more specific than innate responses, and also generate immunological memory. These latter features, which provide enhanced protection upon re-infection with the same pathogen, are the basis of: A. Vaccines B. Antibiotics C. Systemic shock D. Complement activation E. Phagocytosis
A. Vaccines
Multiple choice: Adaptive immune responses are slow to develop, taking days to weeks after exposure to reach their peak. However, these responses are more specific than innate responses, and also generate immunological memory. These latter features, which provide enhanced protection upon re-infection with the same pathogen, are the basis of: A. Vaccines B. Antibiotics C. Systemic shock D. Complement activation E. Phagocytosis
A. Vaccines
What accounts for the transition from IgM to IgD on a B-cell surface?
Alternative splicing of pre-mRNA
Which statement is not correct regarding the fate of B2 cells during or after activation
Although both extra-follicular and germinal center B cells can differentiate into plasma cells, only GC B cells can also differentiate into memory B cells
Define PROTEASE?
An enzyme that breaks down proteins and peptides.
16. Which of the following isotypes of antibodies is the largest? A. IgM B. IgG C. IgA D. IgE E. IgD
Answer: A
16. Which of the following statements BEST differentiates innate and adaptive immune responses? A. Innate responses are stronger during the primary and less important during the secondary response, while adaptive responses are less robust during primary responses and stronger during secondary responses. B. Innate responses are weaker during the primary and more robust during the secondary response, while adaptive responses are stronger during the primary and weaker during secondary responses. C. Innate responses are slower and weaker than adaptive responses. D. Adaptive responses are slower and weaker than innate responses. E. Adaptive responses are required for effective immune responses, while innate responses are not required.,
Answer: A
17. Which of the following cell types is responsible for regulating responses against intracellular pathogens? A. TH1 B. TH2 C. TH17 D. TFH E. Plasma cell
Answer: A
3. Receptors that are multivalent tend to bind to their ligands more strongly than receptors with a single binding site. What is the term used to describe this phenomenon? A. Avidity B. Valency C. Affinity D. Magnetism E. None of the above
Answer: A
19. Whether an immunoglobulin is secreted or membrane bound is directly determined by: A. the sequence of the DNA in the Ig locus. B. mRNA splicing. C. the kind of B cell is producing it. D. DNA rearrangement. E. GPI anchors
Answer: B
19. Which of the following cell types is responsible for regulating responses against predominantly extracellular pathogens? A. TH1 B. TH2 C. TH17 D. TFH E. Plasma cell
Answer: B
23. Which of the following descendants of the CLP act in the innate immune response? A. T cells B. NK cells C. B cells D. Plasma cells E. All of the above
Answer: B
25. Which of the following contains the MOST ITAMs? A. CD3γ B. CD3δ C. CD3ζ D. TCRα E. TCRβ,
Answer: C
7. Which of the following is TRUE about antigens? A. They are always derived from pathogens. B. They are always proteins. C. They are recognized by T cells or B cells. D. They must be microbial in origin. E. They usually cause cellular damage.,
Answer: C
10. Which of the following cell types is MOST commonly associated with recognizing antigens found inside of cells? A. Macrophages B. B cells C. Th cells D. CTL E. Antibodies
Answer: D
3. Which of the following is the pluripotent stem cell that gives rise to all blood cells? A. CLP B. CMP C. CEP D. HSC E. None of the above,
Answer: D
16. Which of the following cell types is responsible for the secretion of immunoglobulins? A. TH1 B. TH2 C. TH17 D. TFH E. Plasma cell
Answer: E
MASP2
Associate with MBL and cleave C4
The antigen receptor on a T cell recognizes a degraded fragment of a protein (i.e., a peptide) bound to a specialized cell surface peptide-binding receptor called an MHC molecule. One key aspect of this system is that the peptides displayed on MHC molecules can be derived from intracellular proteins. This mode of antigen recognition is particularly important in allowing the adaptive immune response to detect infections by: A. Large helminthic parasites in the gastrointestinal tract B. Intracellular pathogens, such as viruses and some protozoa C. Extracellular bacteria that colonize the lungs D. Fungi that form hyphae in the bronchial airways E. Fungal infections in the skin epithelium
B
The classical complement pathway is initiated by C1q binding to the surface of a pathogen. In some cases, C1q can directly bind the pathogen, for instance by recognizing proteins of bacterial cell walls, but in most cases C1q binds to IgM antibodies that are bound to the pathogen surface. How does this IgM-binding feature of C1q contribute to rapid, innate immune responses rather than to slow, adaptive responses? A. C1q induces B lymphocytes to begin secreting antibody within hours of pathogen exposure. B. Natural antibody that binds to many microbial pathogens is produced prior to pathogen exposure. C. C1q binds to C-reactive protein which then binds to IgM on the pathogen surface. D. C1q directly induces inflammation, recruiting phagocytes and antibodies from the blood into the infected tissue. E. C1q binds to dendritic cells in the infected tissue, inducing them to secrete inflammatory cytokines.
B
Most B and T lymphocytes in the circulation appear as small, inactive cells, with little cytoplasm, few cytoplasmic organelles, and nuclei containing condensed inactive chromatin. Yet these cells comprise the adaptive immune response, without which individuals die in infancy. What is the explanation for this apparent dichotomy?
B and T lymphocytes are a heterogeneous population made of cells that express a unique antigen receptor. So, only a small number will respond to any particular pathogen. The majority of circulating cells won't encounter the pathogen that matches their antigen receptor so they remain in a naive and inactive state.
All of the following are true regarding B-cell development EXCEPT:
B cells, like T cells, are MHC class restricted.
The antigen receptor on a T cell recognizes a degraded fragment of a protein (i.e., a peptide) bound to a specialized cell surface peptide-binding receptor called an MHC molecule. One key aspect of this system is that the peptides displayed on MHC molecules can be derived from intracellular proteins. This mode of antigen recognition is particularly important in allowing the adaptive immune response to detect infections by: A. Large helminthic parasites in the gastrointestinal tract B. Intracellular pathogens, such as viruses and some protozoa C. Extracellular bacteria that colonize the lungs D. Fungi that form hyphae in the bronchial airways E. Fungal infections in the skin epithelium
B. T cells can only interact with host cells, so they can only affect pathogens inside the cell.
1.9 Multiple choice: Some Pattern Recognition Receptors (PRRs) recognize nucleic acids, like RNA or DNA. Since our own cells contain human RNA and DNA, the activation of innate immune pathways by these PRRs must rely on additional criteria to discriminate self from nonself. Additional criteria include everything EXCEPT: A. The subcellular location of the RNA B. The presence of adenosine residues in viral RNA C. The methylation state of the DNA D. Unique structures found on viral RNA E. The subcellular location of the DNA
B. The presence of adenosine residues would not discriminate between viral and host RNA, as both types contain these residues.
Our immune system efficiently kills all categories of microbes that attempt to colonize our bodies A. True B. False
B. False
Antibodies, complement proteins, and phagocytic cells provide effective protection against all of the following types of infections in Figure Q2.1, except: A. Fungi B. Virus-infected cell C. Worms D. Bacteria E. Viruses
B. Virus-infected cell
Which statement is correct regarding B cell activation
B2 cells can be activated by BCR-based recognition of protein antigen that is either soluble or cell-bound
How are adaptive immunity and innate immunity similar?
Both use receptors, are pathogen activated, and use humoral and cellular systems
Pathogenic infections induce damage to the host by a variety of mechanisms. While many mechanisms are direct effects of the pathogen, some damaging mechanisms result from the immune response to the infection, as illustrated in Figure Q2.2. Examples of damage caused by the host immune response are:
C
Patients with recurrent infections of Neisseria meningitidis, an extracellular bacterial pathogen that causes meningitis, were examined to determine the underlying cause of their immunodeficiency. A subset of these patients were found to have defects in complement activation on the bacterial surface, a process that for this bacterium is dominated by alternative complement activation leading to C3b deposition on the pathogen surface. When neutrophils from these patients were examined in vitro, the results in Figure Q2.19 were obtained. Based on these data, the identity of the green neutrophil mediator in Figure Q2.19 is likely to be: A. Complement factor B B. The C3 convertase C. Factor P (properdin) D. C3b E. Mannose-binding lectin (MBL)
C
The formation of the C3 convertase is a key step in complement activation that occurs in all three complement pathways. This enzyme cleaves C3 in blood plasma, leading to a conformational change in the C3b fragment that exposes its reactive thioester group. The activated C3b is potentially harmful to the host, if it becomes covalently attached to a host cell, rather than to the surface of a pathogen. This deleterious outcome is largely avoided by: A. The inability of active C3b to diffuse away in the blood plasma. B. The inability of active C3b to covalently attach to the membranes of eukaryotic cells. C. The rapid hydrolysis of active C3b in solution, rendering it inactive. D. The tight binding of active C3b to the C3 convertase. E. The ability of active C3b to recruit phagocytic cells.
C
The skin and bodily secretions provide the first line of defense against infection. One response in this category that is common during upper respiratory virus infections is: A. Production of antibodies B. Infiltration by white blood cells C. Mucus production D. Increased saliva production E. Fever
C
Unlike B lymphocytes, T lymphocytes do not generate a secreted form of their antigen receptor after they are activated and proliferate. This is because the effector functions of T cells are restricted to: A. Responses important in protozoan infections, but not other types of infections B. Interactions with large helminthic parasites, which cannot be phagocytosed C. Interactions with other cells, such as virus-infected cells or other immune cells D. Responses important in mucosal surfaces (e.g., the lung), where antibodies cannot go E. Stimulating B cells and not any other types of cells
C
Both MHC class I and MHC class II molecules are highly polymorphic genes in the human population, with tens to hundreds of different alleles co-existing in the population. This means that a comparison of the MHC protein sequences between two individuals would reveal amino acid differences between one individual and the next. However, these amino acid differences are not randomly distributed along the entire protein, but are clustered in certain locations. The diagram in Figure Q4.16 that most correctly indicates the regions of greatest variability between different MHC proteins (shown by the red highlights) is:
C 4.16
As a family, TLRs can recognize PAMPs associated with a broad array of a different pathogens, including bacteria, viruses, and fungi. Patients with a specific susceptibility to herpesvirus infections have a defect in their ability to respond to viral nucleic acids using TLR-3, TLR-7, or TLR-9, even though these proteins are expressed in the patients' cells. Analysis of the TLRs in macrophages and dendritic cells from these patients would like show which of the arrangements in Figure Q3.11?
C 3.11
Acute phase proteins:
C-reactive protein SP-A SP-D Mannose binding lectin
1.4 Multiple choice: The skin and bodily secretions provide the first line of defense against infection. One response in this category that is common during upper respiratory virus infections is: A. Production of antibodies B. Infiltration by white blood cells C. Mucus production D. Increased saliva production E. Fever
C. Based on common experience, students should know that mucus production is a common response to upper respiratory virus infection. Other responses may also occur, such as fever, production of antibodies, or infiltration of white blood cells, but these are not 'bodily secretions.' Increased saliva is not a symptom common to upper respiratory infections.
The best evidence supporting the concept of immunological memory is: A. The increased numbers of antigen receptors expressed by lymphocytes after primary exposure to an antigen B. The increased levels of cytokines made by lymphocytes after primary exposure to an antigen C. The increased rapidity and magnitude of the secondary response to the same antigen D. The increased swelling of lymph nodes during the secondary response to the same antigen E. The long lifespan of vertebrates, which would be impossible without immunological memory
C. The most compelling evidence supporting the existence of immunological memory is the fact that the secondary response to an antigen is faster, of higher magnitude, and more effective than the response that occurs following an individual's first exposure to that antigen. This is the basis of vaccination.
Both MHC class I and MHC class II molecules are highly polymorphic genes in the human population, with tens to hundreds of different alleles co-existing in the population. This means that a comparison of the MHC protein sequences between two individuals would reveal amino acid differences between one individual and the next. However, these amino acid differences are not randomly distributed along the entire protein, but are clustered in certain locations. The diagram in Figure Q4.16 that most correctly indicates the regions of greatest variability between different MHC proteins (shown by the red highlights) is:
C. (Red in the inner top part)C.
Multiple choice: NK cells express receptors from several families, each of which has multiple members. Some of these receptors are activating and others are inhibitory, and NK cell activation is dependent on the balance of signaling overall. The individual NK cells in an individual: A. Always express a majority of activating versus inhibitory receptors B. Are more potent effectors of cytotoxicity than of cytokine-production C. Each express only a subset of all possible NK receptors D. Are not considered members of the innate lymphoid cell lineage E. Undergo massive proliferation in response to infection, similar to T lymphocytes
C. Each express only a subset of all possible NK receptors
Multiple choice: Unlike B lymphocytes, T lymphocytes do not generate a secreted form of their antigen receptor after they are activated and proliferate. This is because the effector functions of T cells are restricted to: A. Responses important in protozoan infections, but not other types of infections B. Interactions with large helminthic parasites, which cannot be phagocytosed C. Interactions with other cells, such as virus-infected cells or other immune cells D. Responses important in mucosal surfaces (e.g., the lung), where antibodies cannot go E. Stimulating B cells and not any other types of cells
C. Interactions with other cells, such as virus-infected cells or other immune cells
Multiple choice: The skin and bodily secretions provide the first line of defense against infection. One response in this category that is common during upper respiratory virus infections is: A. Production of antibodies B. Infiltration by white blood cells C. Mucus production D. Increased saliva production E. Fever
C. Mucus production
Multiple choice: Streptococcus pneumoniae is a Gram-positive bacterium that colonizes the mucosal surface of the upper respiratory tract in humans. The presence of this bacterium in the nose and throat is widespread in the population, and in most people, colonization with Strep. pneumoniae is asymptomatic. Figure Q2.7 shows a comparison of in vitro growth curves of the wild-type strain of Strep. pneumoniae, as well as a Strep. pneumoniae mutant strain with a defect in one bacterial gene. The graph on the right shows the growth curve following addition of lysozyme during the logarithmic phase of bacterial growth. Which statement could account for the data in these graphs? (IMAGE) A. Strain B is wild-type Strep. pneumoniae, and strain A is a mutant that cannot modify its peptidoglycan to be lysozyme-resistant. B. Strain B is wild-type Strep. pneumoniae, and strain A is a mutant that that expresses increased levels of LPS. C. Strain A is wild-type Strep. pneumoniae, and strain B is a mutant that cannot modify its peptidoglycan to be lysozyme-resistant. D. Strain A is wild-type Strep. pneumoniae, and strain B is a mutant that secretes an enzyme that inactivates lysozyme. E. Strain A is wild-type Strep. pneumoniae, and strain B is a mutant that cannot grow well in vitro.
C. Strain A is wild-type Strep. pneumoniae, and strain B is a mutant that cannot modify its peptidoglycan to be lysozyme-resistant.
Multiple choice: The antibody surface involved in antigen binding varies depending on the size and nature of the antigen. This surface can be concave or flat, and sometimes, can have extended protrusions. This is accomplished by: A. Flexibility in the hinge regions of the antibody allowing rotation of the antigen-binding sites B. Some antibodies using V region framework sequences instead of the CDRs to bind antigen C. The ability of different CDR sequences to form many structurally distinct shapes and surfaces D. The ability of the same heavy chain to pair with different light chains E. The differential usage of κ versus λ light chains, as κ chains form concave binding sites whereas λ chains make flatter surfaces
C. The ability of different CDR sequences to form many structurally distinct shapes and surfaces
Multiple choice: The first pattern recognition receptor (PRR) important in innate immune responses was discovered in the fruit fly Drosophila melanogaster. Stimulation of this receptor, called Toll, induces: A. The synthesis of prostaglandins and leukotrienes B. The inflammatory response in Drosophila hemolymph vessels C. The production of antimicrobial peptides D. The recruitment of phagocytic cells to the site of infection E. The activation of Drosophila complement
C. The production of antimicrobial peptides
Structurally, mannose-binding lectin (MBL) is most similar to _________?
C1q
Structurally, mannose-binding lectin (MBL)is most similar to _________?
C1q
To which of the following is MBL most structurally similar?
C1q
C4b, C2a, C3b
C5 convertase
A T cell line growing in culture is subjected to a chemical mutagen, and individual mutant lines are derived from this population. The individual mutant cell lines are each screened for their ability to proliferate in response to stimulation with antibodies to the T-cell receptor plus CD28 (anti-CD3 + anti-CD28). In addition, the cells are treated with varying doses of added IL-2, and three days later, T cell proliferation is measured by 3H-thymidine incorporation (cpm). The data for one mutant line and the wild-type control are shown in the figure below. Based on the data, the gene that is defective in this mutant T cell line most likely encodes _____________________.
CD25, also known as the IL-2 receptor alpha chain
B7 molecules bind
CD28
Match the following molecules on antigen-presenting cells to their binding partners on T cells: B7 molecules
CD28
What is the receptor on T cell surface that binds to B7 family molecules on a professional antigen-presenting cell?
CD28
Which of the following is a molecule that is NOT targeted for checkpoint blockade?
CD28
Which of the following molecules would double-negative T cells fail to express?
CD4
Which of the following molecules would double-negative T cells never express?
CD4
The immunoglobulin domain provides critical structure to Vh and Vl regions of antibody chains, allowing for a great deal of variability in the length and sequence of the loops connecting the beta strands of the Ig domain. These regions are called
CDRs
Protein HLA-DM displaces _____ from MHC class II molecules in endosomal compartments.
CLIP
Attracts B-cells to B-cell zones in lymph nodes
CXCL13
How are inactive Cathelicidins made active?
Cathelicidin is activated by proteolytic cleavage only when primary and secondary granules are induced to fuse with phagosomes, where it is cleaved by neutrophil elastase that has been stored in primary granules of Neutrophils.
Where are Cathelicidins made and why?
Cathelicidins are made constitutively by neutrophils and macrophages. Cathelicidins are made in response to infection by keratinocytes in the skin and epithelial cells in the lungs and intestine. They are made as inactive pro- peptides composed of two linked domains and are processed before secretion
Immune response against gluten in food, activated CD4 T cells secrete IFN-γ, leading to intestinal inflammation
Celiac disease
A common mechanism by which sensor cells in the host detect micro-organisms relies on the production of unique microbial components not found in the host. Propose a strategy by which a clever microbe could evade this type of response.
Create a blocking method to the sensor cells.
Most normal tissues contain resident macrophages, and connective tissue sites in the gastrointestinal tract and the lung contain large numbers of these cells. Yet the blood also contains a high number of circulating 'classical' monocytes that can differentiate into macrophages after entering tissues. These circulating monocytes function to: A. Phagocytose and kill pathogens in the blood B. Line the endothelial surfaces of the blood vessels with phagocytic cells C. Enter lymph nodes and patrol for infecting microbes in these organs D. Amplify the local innate immune response by entering tissues that are infected E. Differentiate into dendritic cells during an inflammatory response
D
The mucosal tissues of the body have their own unique set of immune structures that function as sites for initiating adaptive immune responses. The necessity for mucosa-associated lymphoid tissues to have unique cell types (M cells) and structures is because: A. The mucous layer lining mucosal surfaces makes it difficult for normal antigen-presenting cells to function. B. The epithelial surfaces that line the gut, lungs, and nasal passages prevent antigen-presenting cells from accessing microbes and microbial products. C. The epithelial cells found in mucosal tissues are distinct from those that provide barrier functions to the skin. D. Mucosal sites, where most pathogens access the body, are exposed to vast numbers of diverse microbes. E. Mucosal tissues lack innate sensor cells that can respond to PAMPs and provide short-term innate immune protection.
D
Which of the following gene segments is NOT found in the mouse IgL loci?
D
A chromosome on which T-cell receptor α chain gene rearrangement has occurred lacks which of the following gene segments? (Hint: T-cell receptor αchain is comparable to Ig light chain)
D (diversity)
What molecules do H-FICOLIN recognize on pathogens?
D-FUCOSE and GALAZTOSE, and has only been linked to activity against the Gram-positive bacterium Aerococcus viridans.
1.1 Multiple choice: In patients with lymphomas, the cancer cells invade the bone marrow and destroy the environment required for normal hematopoiesis. This leads to bone marrow failure, which disrupts the production of hematopoietic cell lineages. All of the following cell types would be affected by this EXCEPT: A. Red blood cells B. Macrophages C. Lymphocytes D. Endothelial cells E. Granulocytes
D. Hematopoietic stem cells in the bone marrow give rise to all the blood cell lineages, including erythrocytes (red blood cells), myeloid cells (macrophages and granulocytes), and lymphocytes. Endothelial cells, which comprise the blood vessel walls, are not derived from hematopoietic stem cells.
Multiple choice: Immunodeficiency diseases occur when individuals have defects in leukocyte adhesion to inflamed endothelial cells, thereby impeding the extravasation of phagocytes into infected tissues. When neutrophils from one class of these patients were isolated and tested using in vitro assays for neutrophil-endothelial cell interactions and extravasation, it was found that the neutrophils could slowly roll along the endothelial vessel wall but were unable to arrest and migrate across the endothelium. The most likely protein deficient in these neutrophils is: A. ICAM-1 or ICAM-2 B. P-selectin C. E-selectin D. An integrin E. Sulfated sialyl-LewisX
D. An integrin
Scaffold proteins are often phosphorylated at multiple sites, allowing the recruitment of several different signaling proteins. In antigen receptor signaling pathways, this mechanism is used to bring enzymes in close proximity to their substrates. Termination of this signaling mechanism would be most efficiently accomplished by: A. Ubiquitination of the scaffold protein, leading to its degradation B. Binding of the enzyme to a GTPase activating protein (GAP) C. Depletion of the substrate due to enzyme catalysis D. Dephosphorylation of the scaffold by a phosphatase E. Ubiquitination of the enzyme by K63-linkage of polyubiquitin
D. Dephosphorylation of the scaffold by a phosphatase
Humans with defective expression of the integrin LFA-1 have an immunodeficiency disease characterized by the failure of lymphocytes and granulocytes to migrate to tissues at sites of infection or inflammation. A similar immunodeficiency would be expected if individuals had mutations disrupting the gene for: A. CD3 B. The complement receptor, CD21 C. WASp D. Rap1 E. SLP-76
D. Rap1
An infant with recurrent bacterial and fungal infections is suspected to have an immunodeficiency disease. Within two days after exposure to a pathogen, the organisms have proliferated to dangerous levels requiring immediate systemic antibiotic treatment. It is unlikely that this infant has a defect in B or T lymphocyte responses to the infection because: A. Bacteria and fungi do not require B cell or T cell responses for their clearance. B. Bacteria and fungi are not efficiently transported to draining lymph nodes to initiate adaptive immune responses. C. Systemic infections of bacteria and fungi are usually cleared by the spleen. D. The defective immune response occurs too rapidly following infection to be due to a defect in B or T lymphocytes responses. E. Adaptive immune responses require dendritic cells to take up and degrade pathogens.
D. The defective immune response occurs too rapidly following infection to be due to a defect in B or T lymphocytes responses.
Which of the following represents the earliest stage in T-cell development?
DN
What protein recruits and activates Artemis to allow cleavage of the DNA hairpin during recombination?
DNA-PK
During what step of complement activation does a pore form in the membrane of the pathogen?
During formation of the membrane attack complex (MAC)
Since the cellular responses of the innate immunity act over several days, what happens to the adaptive immune response during this time?
During this time, the adaptive immune response may also begin if antigens derived from the pathogen are delivered to local lymphoid tissues by dendritic cells.
An infection in the skin, such as a pimple, often produces pus. The major component of pus is: A. Toxic oxygen molecules released by macrophages B. Toxic nitrogen molecules released by macrophages C. NETs released by neutrophils D. Dead epithelial cells killed by lysozyme E. Dead and dying neutrophils
E
Many different viruses encode proteins that function to down-regulate MHC class I expression on host cells following infection with the virus. This immune evasion mechanism allows the virus to hide from CD8 T lymphocytes that normally detect virus-infected cells by using their T cell antigen receptor to recognize viral peptides bound to MHC class I proteins on the surface of the infected cell. To counteract this immune evasion strategy, NK cells have: A. Activating receptors that recognize MHC class I proteins B. A mechanism to secrete antiviral peptides C. Inhibitory receptors that recognize viral capsid proteins D. Activating receptors that recognize viral capsid proteins E. Inhibitory receptors that recognize MHC class I proteins
E. NK cells express both activating and inhibitory receptors, and it is believed that their decision to kill a target cell depends on the relative balance of these two types of signals. When the activating signals are dominant over the inhibitory signals, the NK cell will kill that target cell. Normal host cells constitutively express high levels of MHC class I molecules, and therefore are poor targets for NK cells. However, when a virus infection causes down-regulation of MHC class I proteins on the infected cells, the engagement of inhibitory receptors for MHC class I proteins is lost, tipping the balance in favor of the activating signals. This leads to NK cell killing of the virus-infected target cell.
Neutrophil defensins are: A.Anti-toxins B.Oxygen-dependent C.Enzymes D.Glycolipids E.Short peptides
E. Short peptides
Even when the complement cascade fails to proceed beyond generating the C3 convertase, complement activation is effective at inducing pathogen uptake and destruction. This process of immune protection is mediated by:
Engagement of complement receptors on phagocytes by C3b and its cleavage
Even when the complement cascade fails to proceed beyond generating the C3 convertase, complement activation is effective at inducing pathogen uptake and destruction. This process of immune protection is mediated by:
Engagement of complement receptors on phagocytes by C3b and its cleavage products which promote phagocytosis.
T or F: In negative selection, B cells that interact weakly with self-antigens will either go anergic or enter a state of immunological ignorance. In both cases, the B cells are unresponsive to the antigens, so anergy and immunological ignorance are two names for the same phenomenon.
False
T or F: Like other antibodies, IgE is mainly found in body fluids
False
T or F: Mucosal surfaces and external epithelia are major routes of pathogenic infection. Mucosal surfaces are found in tissues such as the gastrointestinal tract, the reproductive tract and the mouth and respiratory tract. While the mouth and respiratory tract are routes of virus but not bacterial infections, the gastrointestinal tract is the route for bacterial but not virus infections.
False
T or F: Multiple mechanisms provide a series of checkpoints that function to maintain immunological self-tolerance. A breakdown in any one of these mechanisms is likely to lead to autoimmunity.
False
T or F: Naive T cells scan the dendritic cells in the cortical region of the lymph node as they migrate. The initial encounter of T cells with dendritic cells is mediated by interactions between the T-cell receptor and the peptide:MHC complexes on the dendritic cell.
False
T or F: The C3 convertase amplifies the process of complement activation by generating large amounts of C3b and cleaving large numbers of C5 molecules.
False
True/False: B-cell receptors and T-cell receptors share a mechanism for generating diversity, and also share overall structural homology both in their V domains and their C domains. This is because the two proteins have nearly identical functions in the immune responses mediated by their respective cell types.
False
True/False: The antibody protein has two functional domains, one for antigen binding and a second to confer specific effector functions. These two functional domains are encoded by the antibody light chain and antibody heavy chain polypeptides, respectively.
False
True/False: The classical and lectin pathways of complement activation converge at the step of C3 activation. However, the initiating steps of each pathway use protein components and enzymatic mechanisms that share no similarity with each other.
False
True/False: The different classes of immunoglobulins differ in the sequences of their heavy chain constant regions. As a result, each class of antibody has distinct effector functions. Nonetheless, they are all found at about equal concentrations in the serum of healthy individuals.
False
True/False: The generation of a complete coding sequence for an antibody heavy chain involves a lymphocyte-restricted process of DNA rearrangement that links V, D, and J gene segments together to form the exon that encodes the heavy chain V region. A similar type of DNA rearrangement is also utilized for the simultaneous expression of IgM and IgD antibodies by the same B cell.
False
True/False: The invariant chain protein, Ii, has only one function in MHC class II antigen presentation. This function entails Ii protein occupying the peptide-binding site of each newly synthesized class II protein, thereby preventing nascent MHC class II proteins from binding peptides or misfolded proteins in the endoplasmic reticulum.
False
Once B cells begin secreting antibodies, they cease dividing and have a life-span of only a few days.
False NOTE: B cells proliferate in the primary focus for several days, and this constitutes the first phase of the primary humoral immune response. Some of these proliferating B cells differentiate into antibody-synthesizing plasmablasts in the primary focus. Plasmablasts are cells that have begun to secrete antibody, yet are still dividing and express many of the characteristics of activated B cells that allow their interaction with T cells.
1.2 True/False: Our immune system efficiently kills all categories of microbes that attempt to colonize our bodies.
False. Not all microbes are pathogens, and our immune system does not attempt to eliminate all non-pathogenic microbes. Consequently, many body surfaces are colonized by large numbers of non-pathogenic microbes. These are called commensal micro-organisms, and they are found in places like the gastrointestinal tract, the skin, and the oral mucosa.
True/False: Our immune system efficiently kills all categories of microbes that attempt to colonize our bodies.
False. Not all microbes are pathogens, and our immune system does not attempt to eliminate all non-pathogenic microbes. Consequently, many body surfaces are colonized by large numbers of non-pathogenic microbes. These are called commensal micro-organisms, and they are found in places like the gastrointestinal tract, the skin, and the oral mucosa.
The first drug treatment for HIV licensed in the US was zidovudine (AZT), a reverse transcriptase inhibitor. However, AZT has now been completely replaced by HAART as the recommended treatment for HIV-infected individuals. The use of HAART, rather than AZT, is preferred because:
HAART is a combination therapy that reduces the possibility of viral escape mutants
Which cytokine is produced by TH1 cells?
IFN-γ
What do TH1 cells secrete?
IFNgamma
In the case of extracellular bacteria infections, ILC3 is activated by tissue-resident dendritic cells and macrophages to produce the cytokine:
IL-22
The five classes (isotypes) of immunoglobulins comprise
IgA, IgD, IgE, IgG, IgM
Which of the following statements is TRUE of IgE?
IgE binds strongly to mast cells
At what stage of development does a B cell begin to display an IgM receptor?
Immature B Cell
__________ immune response begin responding within hours of parasite exposure.
Innate
TLR4 recognizes bacterial wall component ____.
LPS
Endothelial cell activation
Local secretion of TNFa and other cytokines
CD4 positive T cells recognize their antigen presented by which molecules?
MHC Class II (CD8 recognize MHC class I)
NK cells can be activated following recognition of a virus-infected cell, if that cell has down-regulated expression of MHC class I proteins on its surface. However, NK cells can also recognize infected cells or tumor cells, even if they still express MHC class I proteins. In this latter case, activating receptors on NK cells are recognizing:
Molecules on the target cell up-regulated by cellular or metabolic stress
Human cells in the upper respiratory tract are expressing abnormal levels of surface MHC proteins due to a developing viral infection. Which cell type listed below is most likely to recognize the cells as infected based on altered MHC levels
NK cells
What are the PRRs in the cytosol and what do they sense?
NOD like receptors. They sense bacterial ligands
You have antibodies labeled with different fluorescent dyes to detect CD4 and CD8 molecules. You have used these antibodies for analysis of cells from the thymus and the blood of two strains of mice. Please draw the expected FACS test results for a normal strain and a strain with a genetic defect in the RAG1 gene
NOT SURE
The classical complement pathway is initiated by C1q binding to the surface of a pathogen. In some cases, C1q can directly bind the pathogen, for instance by recognizing proteins of bacterial cell walls, but in most cases C1q bings to IgM antibodies that are bound to the pathogen surface. How does this IgM-binding feature of C1q contribute to rapid, innate immune responses rather than to slow, adaptive responses?
Natural antibody that binds to many microbial pathogens is produced prior to pathogen exposure.
Strong adhesion
Neutrophil LFA-1 with endothelial ICAM-1
Diapedesis
Neutrophil squeeze between endothelial cells
Production of antimicrobial peptides
Paneth cells
Pathogenic organisms cause damage to the host by a variety of mechanisms, depending on the category of the pathogen and its mode of replication in the host. Give an example of two different types of pathogens that are unlikely to be dealt with by the same mechanism of immune protection.
Pathogenic organisms that are very small (viruses, intracellular bacteria, single-cell parasites) will replicate inside host cells, and often induce cell lysis. Slightly larger pathogens are usually extracellular bacteria or fungi. These extracellular microbes cause damage by releasing toxins into the circulation. The largest pathogens are the helminthic parasites, which are too large to invade host cells. These organisms damage tissues by forming cysts that promote destructive responses in the tissues. In each case, the immune mechanisms required to eliminate the pathogen are different. Most notably, the mechanisms required to eliminate intracellular pathogens are different than those needed to eliminate extracellular pathogens.
Type of allergic contact dermatitis caused by lipid-soluble chemicals that alter intracellular proteins, primarily CD8 T cell driven
Poison ivy rash
Hyperacute graft rejection is caused by
Preformed antibodies
What determines if a particular cell will respond to a particular cytokine?
Presence or absence of the receptor for that cytokine
In the late 1990s, compounds that functioned as leukotriene receptor antagonists were approved for the treatment of asthma. The first such drug, zafirlukast, inhibits the actions of a major receptor for leukotrienes, known as CYSLTR1 (cysteinyl leukotriene receptor 1). One would predict that patients on this drug would show (Hint: Leukotrienes are small pro-inflammatory lipid mediators produced and released by activated mast cells).
Reduced bronchoconstriction
Promotes naive T-cell migration outside of thymus
S1P
In hematopoietin receptor family signaling, which of the following molecules get phosphorylated, dimerize and translocate to the nucleus where they act as transcription factors
STAT components
The lipoteichoic acids of Gram-positive bacterial cell walls and the lipopolysaccharide of the outer membrane of Gram-negative bacteria are not present on animal cells. why is this important?
Since they are not found in animal cells, it is one way that the innate immune system is able to recognize bacteria.
The immune system evolved to protect us against infections from pathogenic microorganisms. However, immune responses can also cause, rather than prevent disease. Give two examples of situations in which an immune response causes a disease, whereas the absence of a response has no consequences.
Sometimes immune responses cause diseases but their absence is a neutral event. 1 examples is allergic responses to food, antibiotics, inhaled substances or metal ions (non-threatening antigens). A 2nd example is autoimmune diseases where a person makes destructive immune responses to self-cells and tissues.
Where do immature B cells finish their maturation?
Spleen
Where do immature B-cells finish their maturation?
Spleen
Wiskott-Aldrich syndrome is an immunodeficiency disease that causes a defect in antibody responses. The most severe defects are in antibody responses to protein antigens, which are dependent on CD4 effector TFH cells providing cytokines to the B cell. The protein defective in individuals with the disease, known as WASp, functions in cytoskeletal reorganization and polarization through its role in promoting actin polymerization. This immune defect could be fixed by a gene therapy approach that restored WASp expression in:
T cells
How do memory cells develop
T cells and B cells from the primary response persist and become reactivated
Which type of T helper cell regulates allergic reactions and protects against extracellular pathogens?
TH2
True/False: Dendritic cells are tissue resident myeloid cells that are highly phagocytic, like macrophages. However, dendritic cells do not play a major role in large-scale pathogen destruction; instead, they are important in initiating adaptive immune responses of T cells.
TRUE
Besides producing LYSOZYMES AND PHOSPHOLIPASE A2, what else do the PANETH CELLS of the intestines produce?
The PANETH CELLS of the gut constitutively produce α-defensins, called cryptdins, which are processed by proteases such as trypsin in humans, before being secreted into the gut lumen.
Define proteolysis
The breakdown of proteins or peptides into amino acids by the action of enzymes.
What of the following can lead to initiation of an adaptive immune response?
The interaction of a naïve T cell with an antigen-presenting cell
What is the main effect of COMPLEMENT activation?
The main effect of complement activation is to deposit large quantities of C3b on the surface of the infecting pathogen, where the C3b forms a covalently bonded coat that can signal the ultimate destruction of the pathogen by phagocytes
The alternate and classical complement pathways differ in which of the following ways?
The mechanisms initiating activation.
How is the spread of a pathogen initially countered?
The spread of a pathogen is often initially countered by an inflammatory response that recruits more effector cells and molecules of the innate immune system out of the blood and into the tissues, while inducing clotting in small blood vessels further downstream so that the microbe cannot spread through the circulation
Which is the best definition of "immunity"?
The state of being resistant to reinfection with a pathogen
What do HISTATINS do?
These short, histidine-rich, cationic peptides are active against pathogenic fungi. More recently histatins were found to promote the rapid wound healing that is typical in the oral cavity,
What happens once inactive Cathelicidins become active Cathelicidins ?
They either remain in the phagosome or are released from the neutrophil by exocytosis.
Which of the following statements is the best example of a primary lymphoid organ?
Thymus
An individual with normal B cells, but an absence of T cells might have a defect in:
Thymus stromal cells
IgE is mostly found in
Tissues right beneath epithelial surfaces
The TCR and BCR are multi-subunit receptor complexes. Experiments examining the synthesis and transport of these receptors to the lymphocyte cell surface have shown that the signaling subunits of each receptor complex are required for transport of the ligand-binding receptor subunits to the cell surface. One possible reason for this stringent control on cell surface expression is:
To prevent surface expression of receptors that will bind ligand but fail to induce signals
.True or False: The classical and lectin pathways of complement activation converge at the step of C3 activation. Moreover, the initiating steps of each pathway use protein components and enzymatic mechanisms that share high similarity with each other.
True
Infectious diseases differ in their symptoms and outcome depending on where the causal agent replicates within the body- the intracellular or extracellular compartment- and what damage it does to the tissues.
True
T/F: Chimeric antigen receptor (CART) T cell therapy often fuses variable region from an immunoglobulin to intracellular signaling domains such as ITAMs, therefore, those chimeric antigen receptors can recognize target molecules other than peptide:MHC molecules.
True
True/False: In the absence of an infection, most granulocytes (neutrophils, eosinophils, basophils) are found circulating in the blood, whereas other subsets of myeloid cells reside in tissues.
True
True/False: Innate lymphoid cells and NK cells are effector cells that respond rapidly after encountering a pathogen. Several different subsets of innate lymphoid cells exist, and each is specialized to respond to a category of pathogen (e.g., viruses, extracellular bacteria, helminthic parasites, etc). Innate lymphoid cells reside primarily in tissues such as the lungs, the lining of the gastrointestinal tract, and the skin, because these sites represent the major routes of entry of pathogens into the body.
True
1.25 True/False: The spleen is a secondary lymphoid organ that performs several functions. In addition to its role as a site for initiating adaptive immune responses, the spleen is important in removing dead or damaged red blood cells from the circulation. Its immune function is important because blood-borne pathogens will not be transported to draining lymph nodes via the lymph fluid.
True. The spleen is important for trapping blood-borne pathogens so they can be taken up and degraded by dendritic cells for presentation to T lymphocytes to initiate adaptive immune responses.
Multiple pathways for regulating complement activation limit the potential damage caused by complement deposition on host cells or cause by the spontaneous activation of complement proteins in the plasma. Genetic deficiencies in these mechanisms often lead to chronic inflammatory diseases, but in some cases can paradoxically lead to increased susceptibility to bacterial infections. This latter outcome may occur because:
Uncontrolled complement activation leads to the depletion of serum complement proteins.
RIG-1 receptors detect:
Viral RNA
Antibodies, complement proteins, and phagocytic cells provide effective protection against all of the following types of infections except
Virus-infected cells
What happens when any of the COMPLEMENT PATHWAYS interacts with a pathogen surface?
When any of the pathways interacts with a pathogen surface, the enzymatic activity of a C3 convertase is generated.
E
[12]. Macrophages express multiple types of receptors on their surface that stimulate phagocytosis of microbes, leading to pathogen internalization and destruction. Many of these receptors, such as Dectin-1, rely on direct recognition of a PAMP on the pathogen surface. However, some receptors that stimulate phagocytosis rely on soluble factors (not associated with the phagocyte membrane) to identify and mark the pathogen for uptake by the phagocyte. One such receptor is: a. The mannose receptor b. The class A scavenger receptor c. The lipid receptor d. The macrophage C-type lectin receptor e. The complement receptor
C
[5]. To which of the following is MBL most structurally similar? a. C3b b. Bb c. C1q d. C5b e. None of the above
How does TNF alpha IL-6/IL-1B work?
activates vascular endothelium and lymphocytes
Artemis
b. Nuclease activity opens the DNA hairpin and generates P-nucleotides
C1
begins the classical pathway
What is the central lymphatic organ?
bone marrow
Avidity
bonus effect of multivalent binding results in stronger binding
V-J rearrangement occurs in:
both B cells and T cells
Cell mediated immunity includes ________________
both Th and Tc cells
C4b2a
c3 convertase
C3
central component of all three pathways
C3a
chemoattractant
The name given to cytokines that recruit cells to move towards areas of inflammation is:
chemokines
Alteration of gene transcription profile
corticosteroids
activated CD8+ T effector cells are also called
cytotoxic T cells
Interference with DNA synthesis
cytotoxic drugs
If an animal were deficient in RAG-1 and RAG-2 which of the following processes would be affected
defects would occur in the V(D)J gene rearrangement leading to no (or negligible) numbers of T or B cells
The mechanism that permits Ig to be synthesized in either membrane bound or secreted form is ___________ (SELECT ALL THAT APPLY)
differential RNA processing
Which scenario correctly describes the order and the location of key processes during thymocyte development
double negative thymocytes enter the thymus in corticomedullary junction while moving through cortical region of the thymus the thymocytes rearrange first the beta and then the alpha chain of their TCR
cGAS-STING senses ____ in the cytosol and produces the cytokine _____.
dsDNA Type I Interferon
What do TLRs bind to?
dsRNA, flagella
In patients with lymphomas, the cancer cells invade the bone marrow and destroy the environment required for hematopoiesis. This leads to bone marrow failure, which disrupts the production of hematopoietic cell lineages. All of the following cell types would be affected by this EXCEPT:
endothelial cells
Even when the complement cascade fails to proceed beyond generating the C3 convertase, complement activation is effective at inducing pathogen uptake and destruction. This process of immune protection is mediated by
engagement of complement receptors on phagocytes by C3b and its cleavage products promoting phagocytosis
Antigenic peptides from extracellular pathogens are processed and presented via
exogenous pathway and presented on MHC class II
All immunoglobulin molecules on the surface of a given B cell have the same isotype.
false
B cell epitopes can be deduced with great accuracy from the primary structure of a protein
false
C3a and C3b are fragments of C3 that are generated by two different enzymes.
false
Expression of the beta-subunit of the IL-2 receptor indicates T cell activation.
false
How is innate immune system different from adaptive?
fast response, fixed, limited specificity, and constant during response
Opsonins are
host-derived proteins that bind the exterior of a microbe that facilitate its engulfment by phagocytes expressing receptors for the opsonin
Omenn syndrome
hypomorphic mutations in RAG1 or RAG2
Invariant NKT cells recognize different glycolipid constituents from microorganisms when they are bound to CD1d and are considered to act as innate immune cells. A key feature of the T-cell receptors expressed on iNKT cells is
iNKT cells have a highly restricted T-cell receptor repertoire, with the majority of cells utilizing the same V alpha and J alpha rearrangement
Infections are nested events in immune responses. For example, when a pathogen breaches containment by anatomical barriers, the result is:
infection
The mechanism of cross-presentation by dendritic cells is an essential pathway for generating CD8+ T cell responses to some intracellular pathogens. If theis pathway did not exist, we would be highly susceptible to
intracellular pathogens that do not infect and replicate in dendritic cells
The antigen receptor on a T cell recognizes a degraded fragment of a protein (i.e., a peptide) bound to a specialized cell surface peptide-binding receptor called an MHC molecule. One key aspect of this system is that peptides displayed on MHC molecules can be derived from intracellular proteins. This mode of antigen recognition is particularly important in allowing the adaptive immune response to detect infections by:
intracellular pathogens, such as viruses and some protozoa
what is the COMPLEMENT SYSTEM?
it is a system of plasma proteins that targets pathogens both for lysis and for phagocytosis by cells of the innate immune system.
Strategies to generate diversity in our ability to mount immune responses include the generation of diverse repertoires of lymphocyte antigen receptors, as well as polygenicity of the MHC locus. THe polygenicity of MHC loci differs from the diversity of lymphocyte antigen receptors in that
it stems from the expression of multiple genes encoding proteins that perform the same function but differ slightly in structure
In B cells, a very large repertoire of receptors is generated by different mechanisms: Primary gene rearrangements: -[jj]: Random V, D and J segments are brought together -Junctional diversity: additional diversity provided by [kk]and nuclease(s)
jj. combinatorial diversity kk. TdT
Which of the following is NOT a property of cytokines?
kinase activity
activated by ficolin
lectin pathway
Which of the following is NOT a member of the first main class of phagocytic cells in the innate immune system?
natural killer (NK) cells
What is the process of OPSONIZATION?
opsonization, refers to coating a pathogen with antibodies and/or complement proteins so that it can be more readily taken up and destroyed by phagocytic cells.
What does basophil do?
promote allergic response
IL-4, IL-5, and IL-6 all induce proliferation of B cells. This type of action is said to be
redundant
Mature but naive B-2 cells are most commonly found in the
secondary lymphoid organs
The pattern recognition receptors on cells of the innate immune system are genetically encoded, meaning that their sequences and specificities are determined prior to the development of the individual. In contrast, the antigen receptors of B and t lymphocytes arise from a random rearrangement process that occurs differently in each lymphocyte as it develops. One potential problem entailed by the random process that generates lymphocyte antigen receptors is the possibility that
some antigen receptors might recognize the individuals on cells or antigens
Which of the following is not a mechanism that ensures central tolerance during lymphocyte development
suppression of autoreactive thymocytes by T reg cells
Licensing on an NK cells refers to:
testing an NK cell to ensure that it will not target healthy host cells.
Which domains form the peptide binding groove of the MHC II molecules
the alpha 1 and beta 1 domains
Affinity
the binding of a nonvalent Fab Fragment to one binding site on an antigen
Recombination signal sequences are composed of conserved heptamer and nonamer separated by either 12 or 23 bp spacer sequences. These sequences flank the V, L, and D gene segments in the BCR gene locus. The 12/23 rule of V(D)J recombination ensures that
the correct assembly of gene segments so that a Vh recombines to a Dh and not to another Vh
Individuals with defects in T cell development have a severe immunodeficiency disease called SCID (severe combined immunodeficiency disease). In these individuals, the absence of all T cells causes defects in both cell-mediated (T cell-based) and humoral (antibody-based) immune responses. The defect in antibody response in SCID patients is due to:
the important role of T follicular helper cells in generating protective antibody responses
The best evidence supporting the concept of immunological memory is:
the increased rapidity and magnitude of the secondary response to the same antigen
Large clinical trials have been performed to compare the vaccine ... One difference in the immune response elicited by live-attenuated versus the inactivated vaccine is:
the live-attenuated vaccine elicits antiviral CD8 effector responses but the inactivated vaccine does not
Which of the following statements about the MHC locus is incorrect
the locus codes for both chains of the MHC Class I molecule
S1P1 receptor is upregulated by naïve T cells and B cells after 12-18 hours if they fail to encounter antigen in the lymph node. This means all of the following EXCEPT:
the naïve cells will die by apoptosis.
valency
the number of binding site (at once) on an antigen can also influence avidity
Which of the following is true of MHC Class I molecules
the peptide is held in the cleft of the MHC molecule by anchor residues at the N and C terminus
Some species, like camels, alpacas, and llamas, have evolved variant forms of immunoglobulin proteins that retain the ability to bind to antigens. While overall the antibodies made by these animals are simpler than human or mouse antibodies, an important feature conserved among all of these antibodies is:
the presence of exactly three constant region domains
Which is the best definition of immunity
the state of being resistant to reinfection with a pathogen
Several mechanisms ensure that complement activation will proceed only on ...
the surface of a pathogen or on damaged host cells, and not on normal host cells and tissues.
There are five classes of antibodies, which are distinct from one another based on what
the type of incorporated heavy chain
The human MHC locus is one of the most polymorphic regions of the genome. What does this mean
there are many different alleles of these genes
All the following are characteristics of MHC Class II molecules except
they are expressed constitutively on most nucleated cells
what are propeptides?
they are inactive proteins/peptides that can be turned into an active form by post-translational modification. The name of the precursor for a protein is often prefixed by pro
A large protein antigen can generally be bound by many different antibody molecules simultaneously
true
Most antigens induce a response from more than one T cell or B cell (more than one clone, or version of a TCR or BCR).
true
The C3 convertase of the alternative complement pathway can be formed using C3b created by any pathway, amplifying the overall magnitude of complement activation regardless of which of the three pathways initiated the complement activation initially.
true
The extravasation of neutrophils into tissues at sites of infection or inflammation requires changes to both the endothelium and to the neutrophil that are induced by chemokines and cytokines produced in the infected tissue.
true
The hypervariable regions make significant contact with epitope
true
Naive B and T lymphocytes are small, quiescent cells with little cytoplasm and low metabolic activity. Yet within hours after being activated following encounter with their antigen, these cells enlarge and up-regulate many biosynthetic and metabolic pathways. Approximately one day later, the cells began dividing, and for several days they are the most rapidly dividing cells in the body, undergoing 2-4 rounds of cell division every day. In order to maintain this phenomenal rate of cell division, lymphoblasts must:
up-regulate synthesis of mRNA and proteins, some of which encode for glucose transporters and enzymes used for glycolysis
Who does cytotoxic T cell fight?
viruses and intracellular bacteria in cytosol
Who do antibodies fight?
viruses, parasites, and bacteria in phagosome
Individuals that lack all T cells have the most severe form of immunodeficiency (SCID) and will not survive past their first birthday without a bone marrow transplant from a healthy donor. These individuals fail to make antibody responses to the normal childhood vaccines because:
Most antibody responses require T-cell help for the B-cells
What happens to most microorganisms that succeed in crossing the epithelial surface?
Most of the microorganisms that succeed in crossing an epithelial surface are efficiently removed by innate immune mechanisms that function in the underlying tissues, preventing infection from becoming established. I
A mouse is infected with staphylococcal bacteria through a laceration in the skin of its paw. Dendritic cells are isolated from the tissue at the site of infection, and are incubated together with naïve staphylococcal-specific CD4 T cells. Seventy-two hours later, the proliferation of the CD4 T cells is measured as a readout for T cell activation. Surprisingly, the T cell response is quite poor compared to the response observed when the same T cells are mixed with a comparable number of dendritic cells isolated from the draining lymph node of the infected mouse. A comparison of the dendritic cells isolated from the two different sites would reveal:
Much higher levels of MHC and B7 molecules on the lymph node dendritic cells than those from the infected tissue
The mucosal tissues of the body have their own unique set of immune structures that function as sites for initiating adaptive immune responses. The necessity for mucosa-associated lymphoid tissues to have unique cell types (M cells) and structures is because:
Mucosal sites, where most pathogens access the body, are exposed to vast numbers of diverse microbes
Match the primary immunodeficiency diseases with the defective mechanism: MHC class I deficiency
Mutations in genes encoding TAP1, TAP2, or tapasin
Match the primary immunodeficiency diseases with the defective mechanism: X-linked Severe Combined Immunodeficiency (XSCID)
Mutations in the gene IL2RG
Two strains of mice were infected with 5 104 PFU of Influenza A virus, and the survival data shown in Figure Q3.31 were obtained. Next, both strains were infected again with Influenza A, and levels of type I interferons (IFN- and IFN-) were measured and found to be similar between the two strains. Likewise, cells from both strains expressed similar levels of the IFN-/ receptor (IFNAR). Which of the following proteins might be more highly expressed in strain B than in strain A following Influenza A infection?
Mx-1
TLR4 activation eventually leads to the activation of which transcription factor?
NF-kB
When T cells express defective ER calcium sensor protein, they secrete very little IL-2 because activation of one of the following transcription factors is compromised. That transcription factor is:
NFAT
When T cells express defective ER calciumsensor protein, they secret very little IL-2 because activation of one of the following transcription factors is compromised. That transcription factor is:
NFAT
The activation of __________ by TLRs alerts the immune system to presence of bacterial parasites.
NFkB
Non-classical MHC molecules are often found on the surface of stressed cells. Instead of T-cell receptors, they may engage NK receptors. What is the receptor for type I MHC molecules MIC-A/-B?
NKG2D
Non-classical MHC molecules are often found on the surface of stressed cells. Instead of T-cell receptors, they may engage NK receptors. What is the receptor for type I MHC molecules MIC-A/B?
NKG2D
Activation of which pattern recognition receptor (PRR) does NOT lead to activation of transcription factors (e.g. NF-κB, IRF3)?
NLRP3
NOD1 and NOD2 are cytoplasmic sensors of bacterial products such as muramyl dipeptide (MDP), a constituent in the peptidoglycans of most bacteria. These sensors are highly expressed in epithelial cells that line the body surfaces that pathogens must cross to establish an infection. Interestingly, a subset of patients with an inflammatory bowel disease called 'Crohn's disease' have inactivating mutations in NOD2. Why might this deficiency in NOD2 lead to chronic inflammation in the gut?
NOD2 is highly expressed in the Paneth cells of the gut, where it regulates the expression of potent antimicrobial peptides such as the defensins. Since NOD2 recognizes bacterial components that are found in most strains of bacteria, not just pathogenic microbes, it is likely that NOD2-induced antimicrobial peptide production is occurring constitutively in response to the gut microbiota. This constitutive production of antimicrobial peptides at the intestinal epithelium is an important component of maintaining the natural barrier function of the gut epithelium. In the absence of this, barrier function is weakened, leading to an increased prevalence of microbes crossing the epithelial barrier and inducing an inflammatory response by stimulating the other innate sensors. This chronic inflammation is the hallmark of Crohn's disease.
The classical complement pathway is initiated by C1q binding to the surface of a pathogen. In some cases, C1q can directly bind the pathogen, for instance by recognizing proteins of bacterial cell walls, but in most cases C1q binds to IgM antibodies that are bound to the pathogen surface. How does this IgM-binding feature of C1q contribute to rapid, innate immune responses rather than to slow, adaptive responses?
Natural antibody that binds to many microbial pathogens is produced prior to pathogen exposure. Natural antibody, which is primarily of the IgM class, is produced in the body prior to pathogen exposure. These antibodies are widely reactive with many microbial pathogens, although they generally have low affinity for the pathogen. However, since IgM is a pentamer of IgM monomers, each IgM pentamer has 10 binding sites for antigen, allowing even low affinity antibodies to bind, due to the increased avidity of multiple binding sites. This natural antibody will then recruit C1q, leading to complement activation. Since the natural antibody pre-exists prior to pathogen exposure, this response is rapid and is considered part of the innate immune response.
Antibody-dependent cell-mediated cytotoxicity (ADCC) is an important effector mechanism in immunity to virus infections. This immune pathway has also been exploited for clinical applications. For instance, patients with various disorders, including rheumatoid arthritis and some B cell lymphomas, are treated with an antibody directed at CD20, a surface receptor expressed on all B cells. This antibody leads to the depletion of B cells from the patients by the actions of:
Natural killer (NK) cells
What lymphocytes do first, as soon as they migrate to the lymph nodes?
Naïve lymphocytes sample stromal cells in the lymph nodes; B and T cells are guided by different chemokine interactions to distinct microenvironments: B cells enter the follicles, T cells enter the paracortex; They will scan for antigens using their Ag receptors
Which of the following is not a mechanism of peripheral tolerance?
Negative selection
Which process would be increased in a double transgenic mouse that expresses both a transgenic TCR transgenic as well as the protein that the TCR recognizes?
Negative selection
Upon entering the thymus, thymocytes are classified as __________ with regard to co-receptor; before exiting as single positive, naive T cells, they pass through a period in which they are ______________.
Negative; positive
Proteins found in the circulation travel throughout the body, including the thymus. One example is serum albumin. Developing T cells with T-cell receptors specific for peptides of human serum albumin bound to MHC class II molecules would likely be:
Negatively selected in the thymus and deleted from the mature repertoire
__________describes the action of antibodies whereby antibodies bind to a pathogen and prevent the pathogen from interacting with cell receptors
Neutralization
Inflammatory bowel disease (colitis) is a CD4 T-cell mediated disease that can be transferred to naive mice by administration of effector CD4 T cells that home to the gastrointestinal tract and induce inflammation. Simultaneous administration of neutralizing antibodies to IL-12p40 (a subunit of IL-23) can prevent the disease, as well as neutralizing antibodies to IL-23p19 (another subunit of IL-23). Disease symptoms can be exacerbated by administration of IL-23, but not of IL-12. These data strongly suggest that:
Neutralizing antibodies to IL-17 would prevent disease. NOTE: Yes. The data indicate a key role for TH17 cells and for their dependence on IL-23 to induce disease as the antibody neutralization data shows that both subunits of IL-23 are essential (IL-12p40 and IL-23p19) and that IL-23, but not IL-12, will exacerbate disease.
In type III immune response, both TH17 and ILC3 cells secrete IL-17 to activate:
Neutrophils
Cellular hypersensitivity, primarily T cell driven, can also invoke inflammatory response by binding to TLR4
Nickel allergy
Are θ-defensins found in the the human body?
No because, the single human θ-defensin gene has been inactivated by a mutation.
Some viruses have mechanisms to down-regulate MHC class I protein expression on the surface of cells in which the virus is replicating. This immune evasion strategy might prevent effector CD8 cytotoxic T cells from recognizing and killing the virus-infected cells. Would this immune evasion strategy also prevent the initial activation of virus-specific CD8 T cells?
No, because dendritic cells would take up infected cells and cross-present viral peptides to activate CD8 T cells.
Some viruses have mechanisms to down-regulate MHC class I protein expression on the surface of cells in which the virus is replicating. This immune evasion strategy might prevent effector CD8 cytotoxic T cells from recognizing and killing the virus-infected cells. Would this immune evasion strategy also prevent the initial activation of virus-specific CD8 T cells?
No, because dendritic cells would take up infected cells and cross-prevent viral peptides to activate CD8 T-cells
Does COMPLEMENT only influence the innate immune system?
No, besides acting in innate immunity, complement also influences adaptive immunity.
Are C1q, C1r, andC1s the cleavaged products of C1?
No, these are not cleavage products of C1 but are distinct proteins that together comprise C1
TdT
Non-template addition of N-nucleotides
In mice that lack MHC class I in the thymus, T cell development will show:
Normal number of mature CD4+ T cell, no mature CD8+ T cells
Self-reactive B cells can be eliminated from the repertoire at several stages of B cell maturation, including immature B cells that have already emigrated from the bone marrow into the circulation. This latter stage of tolerance induction is critical because:
Not all self-antigens are expressed or present in the bone marrow during B cell development.
What are the features of an activated conventional dendritic cell when it arrives at the nearby lymph node?
Not phagocytic, high surface expression of MHC and B7 molecules
Artemis
Nuclease activity to open the DNA hairpin and generate P-nucleotides
granule;death receptor
Once a NK cell has identified a target cell, it will kill by: -[u]-dependent killing involving granzyme and perforin -[v]-dependent killing following binding of Fas-L/Fas-receptor
Antigen receptors use multiple mechanisms to recruit signaling proteins to the plasma membrane, where they can propagate downstream signals. In some cases, recruitment of proteins to the membrane is induced following antigen receptor stimulation, whereas other proteins are constitutively associated with the membrane. Name one mechanism that is induced by antigen receptor stimulation, and one that is constitutive, and give an example a protein recruited by each mechanism.
One mechanism induced by antigen receptor stimulation is the binding of the membrane phospholipid, PIP3. PIP3 is generated in response to the phosphorylation of PIP2. Examples include Akt, Itk, and PLC-y. Another one is the phosphorylation of scaffolding proteins in response to antigen receptor stimulation. Examples include Grb-2, Gads, and SLP-76. A constitutive mechanism would be lipid modified proteins interacting in a constitutive manner with the plasma memrane. Examples include small GTPases like Rap-1 and Ras.
Each immunoglobulin (Ig) domain is composed of a structure known as a 'beta-sandwich,' which consists of two beta sheets covalently linked by a disulfide bond. Only a subset of the ~110 amino acids in each domain are required to establish this overall structure, and it is these amino acids that are highly conserved when comparing Ig domains to each other. What might be the advantage of this structure for use as antibody variable domains?
Only a subset of amino acids in an Ig domain are required to assemble the beta-sandwich structure. This allows remaining amino acids to vary between antibody variable domains while still retaining the same overall structure. Conserved amino acids lie in the sequences encoding the beta strands that form each sheet, and cysteine residues used for the disulfide bond. Loops between beta strands can then vary in amino acid sequence between different antibody polypeptides.
When does the adaptive immune system start to respond to pathogens?
Only if an infectious organism breaches these first two lines of defense will mechanisms be engaged to induce an adaptive immune response—the third phase of the response to a pathogen.
Approximately one in every three alpha:beta T cells expresses two different rearranged TCR-alpha chain proteins. Yet T cells are still considered to have 'clonal specificity' for recognizing antigen. The reason for asserting that each T cell has a single functional specificity for recognizing antigen is that:
Only one T-cell receptor expressed by each T cell will recognize peptide presented by self-MHC molecules.
Part of the complement system process is __________, which refers to coating a pathogen with antibodies and/or complement proteins so that it can be more readily taken up and destroyed by phagocytic cells.
Opsonization
In vertebrates, complement activation generally involves a pathogen recognition step followed by a proteolytic cascade that produces the effector proteins that function in opsonization, membrane attack, and inflammation. a) Which of these is likely to be the most evolutionarily primitive aspect of the complement system?
Opsonization The most primitive form of a complement system is one that resembles our alternative complement pathway, with ancestral homologs of C3 and factor B that make a C3 convertase. This provides a mechanism for opsonizing infecting bacteria and increasing their phagocytosis by phagocytic cells. These ancestral homologs of C3 and factor B have been found in echinoderms, and may even have existed in even more primitive organisms such as corals and sea anemones.
what is OPSONIZATION?
Opsonization is a term that refers to an immune process where particles such as bacteria are targeted for destruction by an immune cell known as a phagocyte . The process of opsonization is a means of identifying the invading particle to the phagocyte.
How does COMPLEMENT influence the adaptive immune system?
Opsonization of pathogens by complement facilitates their uptake by phagocytic antigen-presenting cells that express complement receptors; this enhances the presentation of pathogen antigens to T cells. B cells express receptors for complement proteins that enhance their responses to complement-coated antigens,
5;iga;igm;j chain;igd;b cell;ige;pig r or fcn r; transcytosis
Out of the [gg] different isotypes of antibodies, 2 are secreted as multimers. [hh] is secreted as a dimer and [ii] is secreted as a pentamer. Both isotypes form multimers by interacting with the [jj]. IgM and [kk] are both expressed at the surface of mature [ll] cells and are derived from the same pre-mRNA transcript. Mast cells, basophils, and activated eosinophils bear Fcε receptors that bind to [mm] isotype. IgA and IgM isotype antibodies are able to bind to [nn], which actively transports them across the mucosal epithelium by a process called [oo].
Which of the following alterations would result in increased activity of Ras?
Overexpression of GEFs
The first contact of a neutrophil and endothelial cell during neutrophil recruitment is between:
P/E-selectin and sulfated sialyl-Lewis
The first contact of a neutrophil and endothelial cell during neutrophil recruitment is between:
P/E-selectin and sulfated sialyl-Lewisx
What are PANETH CELLS?
PANETH CELLS are specialized epithelial cells in the base of the crypts in the small intestine that secrete many antimicrobial proteins into the gut. Specifically LYSOZYMES AND PHOSPHOLIPASE A2.
Aside from generating diacylglycerol (DAG) and inositol triphosphate (IP3), PIP2 can be converted to PIP3 by PI-3 kinase. PIP3 recruits Akt, Vav, and RasGRP to cell membrane because these proteins contain the domain below:
PH
Both MHC class I and MHC class II molecules are highly polymorphic genes in the human population, with tens to hundreds of different alleles co-existing in the population. This means that a comparison of the MHC protein sequences between two individuals would reveal amino acid differences between one individual and the next. However, these amino acid differences are not randomly distributed along the entire protein, but are clustered in certain locations. The panel in the diagram below that most correctly indicates the regions of greatest variability between different MHC proteins (shown by the red highlights) is: PICTURE
PICTURE C
The image below shows an MHC molecule (in blue) presenting a peptide (in turquoise). Which picture highlights the region of the peptide:MHC that interacts with T cell receptors (as indicated by the black outline)? PICTURE
PICTURE C
Which of the following classes of cell surface receptors are directly encoded in the germline?
PRR
Which of the following is the CORRECT relationship? _______________ on _____________ recognize _________________ on ____________________.
PRRs; macrophages; PAMPs; pathogens
Which description of type I diabetes is TRUE?
Pancreatic beta-islet cells are destroyed by CD8+ T-cells
Enzyme MMP7 cleaves prepro-α-defensin to the active α-defensin. The cell type in the gastrointestinal (GI) epithelium most likely to express the highest levels of MMP7 is:
Paneth cells
Match the following cell types with their specialized functions: Production of antimicrobial peptides
Paneth cells
Which statement is NOT true about mast cells?
Participate in type 3 immune response to eliminate extracellular pathogens through phagocytosis
What statement is NOT true about mast cells?
Participate in type I immune response to eliminate extracellular pathogens
What happens when COMPLEMENT PROTEINS interact with each other?
Particular complement proteins interact with each other to form several different pathways of complement activation, all of which have the final outcome of killing the pathogen, either directly or by facilitating its phagocytosis, and inducing inflammatory responses that help to fight infection.
The effector activities important in eliminating infectious organisms from our bodies can be categorized into four different groups: cytotoxicity, intracellular immunity, mucosal and barrier immunity, and extracellular immunity. Briefly describe why the immune system requires four different effector modules for maximum protection.
Pathogenic microbes can be divided based on host lifestyle. Each lifestyle requires a different effector mechanisms for pathogen eradication. Cytotoxic activity is required to eliminate virus infections, which take place in many cell types. Intracellular immunity is required for pathogens that have evolved to live inside phagocytes. Mucosal and barrier immunity is required for large parasites that enter the body through mucosal sites and can't be engulfed by phagocytes. Extracellular immunity is required for most smaller extracellular pathogens that can be engulfed and eliminated by phagocytes.
1.31 Short answer: The effector activities important in eliminating infectious organisms from our bodies can be categorized into four different groups: cytotoxicity, intracellular immunity, mucosal and barrier immunity, and extracellular immunity. Briefly describe why the immune system requires four different effector modules for maximum protection.
Pathogenic microorganisms can be divided into groups based on their lifestyle in the host. Each of these lifestyles requires a different set of effector mechanisms for pathogen eradication. Cytotoxic activity is required to eliminate virus infections, which can take place in many different cell types in the body. Intracellular immunity is required for pathogens that have evolved to live inside phagocytes. Mucosal and barrier immunity is required for large parasites that generally enter the body through mucosal sites and cannot be engulfed by phagocytes. Extracellular immunity is required for most smaller extracellular pathogens that can be engulfed and eliminated by phagocytes.
1.3 Short answer: Pathogenic organisms cause damage to the host by a variety of mechanisms, depending on the category of the pathogen and its mode of replication in the host. Give an example of two different types of pathogens that are unlikely to be dealt with by the same mechanism of immune protection.
Pathogenic organisms that are very small (viruses, intracellular bacteria, single-cell parasites) will replicate inside host cells, and often induce cell lysis. Slightly larger pathogens are usually extracellular bacteria or fungi. These extracellular microbes cause damage by releasing toxins into the circulation. The largest pathogens are the helminthic parasites, which are too large to invade host cells. These organisms damage tissues by forming cysts that promote destructive responses in the tissues. In each case, the immune mechanisms required to eliminate the pathogen are different. Most notably, the mechanisms required to eliminate intracellular pathogens are different than those needed to eliminate extracellular pathogens.
Pathogenic organisms cause damage to the host by a variety of mechanisms, depending on the category of the pathogen and its mode of replication in the host. Give an example of two different types of pathogens that are unlikely to be dealt with by the same mechanism of immune protection.
Pathogenic organisms, like single-cell parasities, viruses, and intracellular bacteria, that are very small will replicate inside host cells, often inducing cell lysis. Slightly bigger pathogens, like extracellular bacteria and fungi, cause damage by releasing toxins into circulation. Helminthic parasites are too big to invade cells and damage tissues by forming cysts that cause a destructive tissue response. Required immune mechanisms are different for each pathogen, especially between intracellullar and extracellular ones.
Most effector T cells migrate out of secondary lymphoid organs and into tissues to exert their function. In which of the cases shown in the figure below will the TH1 effector cell undergo long-lived interactions with its target cell, an infected macrophage? Assume all of the target cells shown below are infected with the pathogen recognized by the specific TH1 cells.
Picture A
Use the following list to complete the statements that follow: antagonistic, cascade inducible, pleiotropic, redundant, synergistic. IL-2 acts on several cell types thus regulating multiple immune processes. IL-2 is said to be __________ You are a new member of a graduate research lab. Your research is to study the effects of a novel cytokine TNF-mu (TNF-μ). During the course of your research, you discover that TNF-μ induces monocyte maturation, inhibits eosinophil development, and begins a signaling cascade that promotes histamine release. What term best describes the action of TNF-μ on eosinophils? ___________________ B-cell proliferation is triggered by IL-2, IL-4, and IL-5. Each of these cytokines is secreted by activated TH cells thus their action is ________
Pleiotropic Antagonist Redundant
Type of allergic contact dermatitis caused by lipid-soluble chemicals that alter intracellular proteins, primarily CD8 T cell-driven
Poison ivy reaction
Which of the following does NOT occur shortly following oligomerization of the BCR upon antigen binding?
Positioning of CD3 to allow for phosphorylation if its ITAM motifs
Is PROPERDIN a positive or negative regulatory protein?
Positive regulatory protein.
Mycobacteria are intracellular pathogens that have adapted to life inside phagocytic cells, such as macrophages. These intracellular bacteria are taken up by phagocytosis, similar to other pathogens, but the bacteria are not killed. One possible mechanism that could account for this immune evasion by mycobacteria is their ability to:
Prevent fusion of phagosomes with lysosomes
Some pathogenic microorganisms encode proteins, such as the Staphylococcus Protein A, that bind to immunoglobulin constant region domains with high affinity. These microbial proteins provide a benefit to the microorganism by:
Preventing antibodies bound to the microbe from binding to Fc receptors on phagocytes
VDJ recombination occurs during which phase of B cell development?
Pro-B cell
On the cell surface of an antigen-presenting cell, what is the structure recognized by the α:β T-cell receptor?
Processed peptide antigen plus MHC
What is the structure recognized by the αβ T-cell receptor on the cell surface of an antigen-presenting cell?
Processed peptide antigen plus MHC
CCL19/21
Promote naive T cell entry into lymph nodes
Sphingosine-1 phosphate (S1P)
Promote naive T cell migration out of the thymus
Where are PROPERDINS made?
Properdin is made by neutrophils and stored in secondary granules. It is released when neutrophils are activated by the presence of pathogens.
The processing of cytosolic protein for MHC presentation involves:
Proteasome mediated cleavage
The processing of cytosolic protein for MHC presentation involves:
Proteasome-mediated cleavage
The processing of cytosolic protein involves
Proteasome-mediated cleavage
Immunotherapies aimed at promoting anti-tumor immune responses are being developed for tumors of many different tissue or cell-type origins. Interestingly, some of these approaches, when tested in clinical trials, were found to also cause patients to develop autoimmune symptomsrelated to their tumor type. For instance, in patients with malignant skin cancer (melanoma), immunotherapy treatment can develop an autoimmune disorder known as vitiligo, in which T cells attack and destroy melanocytes in the skin, causing depigmentation. These findings indicate that, in some individuals the melanoma-specific anti-tumor T cell responses are directed at:
Proteins normally expressed in melanocytes
what is proteolytic processing
Proteolytic processing is a major form of post translational modification which occurs when a protease cleaves one or more bonds in a target protein to modify its activity. This processing may lead to activation, inhibition or destruction of the protein's activity.
When complement proteins are covalently deposited onto the surface of a bacterium, this can sometimes lead to direct lysis of the bacterium. However, more commonly, the deposition of complement proteins onto the bacterial surface does not directly harm the bacterium. Instead, these complement proteins aid in bacterial elimination by:
Providing a mechanism for phagocytes bearing complement receptors to recognize and ingest the bacterium.
Human primary severe combined immunodeficiencies can arise from recessive mutations, altering the function or expression of which proteins
RAG-1 and RAG-2, Artemis, DNA ligase IV, and IL-2 receptor gamma chain
Which of the following components that are essential for rearrangement of the Ig heavy or Ig light loci, are not utilized in rearrangement of the TCR loci
RAG-1 and RAG-2, Artemis, TdT, and RSS sequences with spacers of 12 bp and 23 bp
How does allelic exclusion prevent multiple heavy-chain rearrangements from occurring in pre-B cells?
RAG1 and RAG2 are down-regulated, and TdT activity is decreasing so that no additional heavy-chain rearrangements may take place
What is the main difference between TLRs and RLRs in viral detection?
RLRs detect viral RNAs produce within a cell, while TLRs detect extracellular viral RNA
Recognize RSS and create single stranded break
Rag1/2
Combinational diversity:
Random V, D and J segments are brought together
Inhibition of cell growth and proliferation by inhibiting mTOR activity
Rapamycin
Do antibodies bind their antigens via noncovalent bonding or via covalent bonding? Please list 3 different types of interactions.
Receptor-Ligand binding occurs via multiple noncovalent bonds. 1) Hydrogen Bonds 2) Ionic Bonds 3) van der Waals interactions
Rag1/2
Recognize RSS and created single stranded break
The innate immune response together with antibodies are generally not effective at clearing infections established by pathogens that replicate inside host cells. The evolution of T cells has provided a means for the immune response to 'see' intracellular infections based on the ability of T cells to:
Recognize pathogen-derived peptides on host MHC surface molecules
rag2
Recognizes RSS and creates single stranded breaks
The formation of a DNA coding sequence for the variable region of Ig involves ___________ (SELECT ALL THAT APPLY)
Recombination of signal sequences DNA rearrangements the 12/23 rule
The compound LE135 is an inhibitor of the retinoic acid receptor, and blocks signaling through this receptor. In a mouse model of inflammatory bowel disease (IBD), inflammation in the gastrointestinal (GI) epithelium is significantly exacerbated if animals are treated with LE135. Analysis of the CD4 T cell subsets found in the GI epithelium of LE135-treated mice compared to controls with IBD would likely show:
Reduced numbers of iTregs in the LE135-treated mice
what is RegIIIα?
RegIIIα kills bacteria directly by forming a hexameric pore in the bacterial membrane (Fig. 2.12). RegIII family proteins preferentially kill Gram-positive bacteria, in which the peptidoglycan is exposed on the outer surface.
Define constitutively
Relating to the synthesis of a protein or an enzyme at a constant rate regardless of physiological demand or the concentration of a substrate.
In healthy adults, neutrophils represent approximately half of their white blood cells. During a bacterial infection, this number often rises to >80%. One factor contributing to this rise is:
Release of neutrophils into the blood from the bone marrow
After T cell receptor activation, the intracellular regions of CD3 are phosphorylated at multiple tyrosine sites. These phosphorylated tyrosines then recruit proteins containing the ____ domain:
SH2
Which statement is not correct regarding somatic hypermutation
SHM occurs in the light zone of the germinal center and results in production of antibodies of different isotypes than IgM
Epithelial surfaces provide the first line of defense against infection by the use of several types of mechanisms. One of the chemical mechanisms used by epithelia is:
Secretion of antimicrobial peptides by epithelial cells
Epithelial surfaces provide the first line of defense against infection by the use of several types of mechanisms. What is a chemical way to fend off pathogens?
Secretion of antimicrobial peptides by epithelial cells
A common mechanism by which sensor cells in the host detect micro-organisms relies on the production of unique microbial components not found in the host. Propose a strategy by which a clever microbe could evade this type of response.
Sensor cells commonly recognize unique microbial components, such as bacterial LPS or other cell wall constituents. A microbe could evade this response by altering its membrane or cell wall components so that they are no longer recognized by the sensor cell receptors.
1.5 Short answer: A common mechanism by which sensor cells in the host detect micro- organisms relies on the production of unique microbial components not found in the host. Propose a strategy by which a clever microbe could evade this type of response.
Sensor cells commonly recognize unique microbial components, such as bacterial lipopolysaccharide or other cell wall constituents. A clever microbe could evade this response by altering its membrane or cell wall components so that they are no longer recognized by the sensor cell receptors.
A common mechanism by which sensor cells in the host detect micro-organisms relies on the production of unique microbial components not found in the host. Propose a strategy by which a clever microbe could evade this type of response.
Sensor cells commonly recognize unique microbial components, such as bacterial lipopolysaccharide or other cell wall constituents. A clever microbe could evade this response by altering its membrane or cell wall components so that they are no longer recognized by the sensor cell receptors.
A common mechanism by which sensor cells in the host detect micro-organisms relies on the production of unique microbial components not found in the host. Propose a strategy by which a clever microbe could evade this type of response
Sensors cells recognize unique microbial components like bacterial lipopolysaccharide and other cell wall parts. Clever microbes could evade this type of response by altering it's membrane or cell wall components to remain invisible to the sensor cell receptors.
Systemic reaction to injection of large quantities of foreign antigen, primarily IgG mediated
Serum sickness
Systemic reaction to injection of large quantities of foreign antigen, primarily IgG-mediated
Serum sickness
What protects healthy host cells from the injurious effects of inappropriate complement activation on their surfaces?
Several negative regulatory proteins, present in plasma and in host-cell mem- branes, called Complement regulatory proteins.
Neutrophil secret defensins, which are:
Short amphipathic peptides
Neutrophil defensins are:
Short peptides
Antibody heavy and light chain polypeptides consist of repeated domains, each of which is ~110 amino acids and folds up into a compact three-dimensional structure known as an 'immunoglobulin domain.' These immunoglobulin domains are
Similar but not identical in amino acid sequence when comparing the domains in a single heavy chain polypeptide
How do Defensins disrupt cell membranes of microbes?
Since defensins have charged and hydrophobic regions (separated),this allows the defensins to interact with the charged surface of the cell membrane and become inserted in the lipid bilayer. Although the details are still unclear, a transition in the arrangement of the defensins in the membrane leads to the formation of pores and a loss of membrane integrity.
Which parasite characteristic is not recognized by a known TLR?
Single stranded DNA
What are two major peripheral organs?
Spleen (white blood cell storage and recycle red blood cells) and lymph nodes (filter lymph)
After production, naïve lymphocytes travel briefly through the blood to the
Spleen; Mucosal associated lymphoid tissue; Peripheral lymph nodes ; Spleen and peripheral lymph nodes; Spleen and mucosal tissues
In recent years, several new vaccines have been developed that are made from purified viral surface proteins, rather than intact or live viruses. They are referred to as subunit vaccines. In order to generate a protective adaptive immune response to a subunit vaccine, the viral protein(s) must be mixed with an adjuvant. The adjuvant functions to:
Stimulate dendritic cells to up-regulate co-stimulatory molecules and migrate to the regional lymph node
Toll-like receptors (TLRs) are important for adaptive immune responses because
Stimulation of TLRs on dendritic cells by pathogen components induces the expression of chemokine receptor CCR7 on the dendritic cell; Expression of CCR7 enables dendritic cells laden with pathogen antigens to migrate from the site of infection to the nearest draining lymph node in response to chemokines produced by the lymph node; Stimulation of TLRs and other receptors on dendritic cells and macrophages also induces the expression of B7 co-stimulatory molecules, which makes these cells into professional antigen-presenting cells that are able to activate naive T cells
Streptococcus pneumoniae is a Gram-positive bacterium that colonizes the mucosal surface of the upper respiratory tract in humans. The presence of this bacterium in the nose and throat is widespread in the population, and in most people, colonization with Strep. pneumoniae is asymptomatic. Wild-type Strep. pneumoniae is naturally lysozyme-resistant because a substantial proportion of GlcNAc residues in its peptidoglycan are deacetylated, and no longer substrates for lysozyme-mediated hydrolysis. shows a comparison of in vitro growth curves of the wild-type strain of Strep. pneumoniae, as well as a Strep. pneumoniae mutant strain with a defect in one bacterial gene. The graph on the right shows the growth curve following addition of lysozyme during the logarithmic phase of bacterial growth. Which statement could account for the data in these graphs?
Strain A is wild-type Strep. pneumoniae, and strain B is a mutant that cannot modify its peptidoglycan to be lysozyme-resistant. Strep. pneumoniae is a Gram-positive bacterium that readily colonizes the human nose and mouth, due to the resistance of its peptidoglycan to degradation by lysozyme, an enzyme that is abundant in tears, saliva, and mucus. Wild-type Strep. pneumoniae is naturally lysozyme-resistant because a substantial proportion of GlcNAc residues in its peptidoglycan are deacetylated, and no longer substrates for lysozyme-mediated hydrolysis. This accounts for the prevalence of Strep. pneumoniae in the upper respiratory tract of healthy humans, where lysozyme is present at high concentrations. When one of these enzymes is missing, as in strain B, the bacteria become lysozyme- sensitive, and are killed by the lysozyme.
Streptococcus pneumoniae is Gram positive bacterium that colonizes the mucosal surface of the upper respiratory tract in humans. The presence of this bacterium in the nose and throat is widespread in the population, and in most people, colonization with Strep. pneumoniae is asymptomatic. Figure Q2.7 shows a comparison of in vitro growth curves of the wild-type strain of Strep pneumoniae, as well as a Strep. Pneumoniae mutant strain with a defect in one bacterial gene. The graph on the right shows the growth curve following addition of lysozyme during the logarithmic phase of bacterial growth.
Strain A is wild-type strep. pneumoniae, and Strain B is a mutant that cannot modify its peptidoglycan to be lysozyme resistant 1st graph, same lines, no lysozyme 2nd graph, lines different, positive lysozyme
The final stages of T cell development occur in the thymic medulla, after the developing cells become CD4 or CD8 single-positive. One important change that occurs during this final maturation is:
Strong signaling through the TCR no longer induces cell death
Which method is most characteristically used by trypanosomes to escape the immune response?
Switching of VSGs (variable surface glycoproteins)
Where are L-FICOLIN and H-FICOLIN made and where do they reside once made?
Synthesized by the liver and circulate in the blood.
For each of the following statements, indicate whether it is true only of B cell epitopes, only of T cell epitopes, or if it is true for both types of epitopes. Assume it is a large antigen. They almost always consist of a linear sequence of amino acids. They are generally located in the interior of a protein antigen They are generally located on the surface of a protein antigen The lose their immunogenecity when a protein antigen is denatured by heat Multiple different epitopes may occur in the same antigen They generally arise from protein antigens Their immunogenecity may depend on the three-dimensional structure of the antigen
T cell epitope T cell epitope B cell epitope B cell epitope BOTH T cell epitope B cell epitope
Which of the following cell types would be LEAST likely to express MHC class II? Please select from the list: B cells, T cells, Dendritic cells, Thymic epithelial cells, Vascular endothelial cells.
T cells
Deficiency in RAG-1 and/or RAG-2 can affect the proper development of which of the following cell types: macrophages, T cells, B cells, NK cells, mast cells.
T cells and B cells
The experiment shown in the figure below uses two strains of mice that differ in their MHC genes. Strain A is H-2a and Strain B is H-2b. Mice of each strain are infected with the virus LCMV, and T cells are isolated at day 8 post-infection. These T cells are mixed with target cells that express either H-2a or H-2b; in each case, the target cells are either uninfected or infected with LCMV. After a four-hour incubation of T cells with target cells, the percentage of target cells lysed by the T cells is shown in the graph. The explanation for the results of this experiment is: GRAPH
T cells from mice of strain A only recognize viral peptides on target cells expressing H-2a.
Which cells interact to regulate antibody production during the adaptive immune response?
T follicular helper and B cells
Wiskott-Aldrich syndrome is an immunodeficiency disease that causes a defect in antibody responses. The most severe defects are in antibody responses to protein antigens, which are dependent on CD4 effector TFH cells providing cytokines to the B cell. The protein defective in individuals with the disease, known as WASp, functions in cytoskeletal reorganization and polarization through its role in promoting actin polymerization. This immune defect could be fixed by a gene therapy approach that restored WASp expression in:
T-cells
In people infected with human cytomegalovirus, class I MHC and beta2-microglobulin are produced, but with very little mature class I MHC is found at the cells surface. Inhibition of which of the following molecules by human cytomegalovirus may account for this phenomenon
TAP
ABC transporters that mediate the ATP dependent transport of peptides into the lumen of the ER.
TAP1/2
Which of the following lists the types of cells that act as cytotoxic effector cells?
TC cells, NK-T cells, and NK cells.
Match the following molecules on antigen-presenting cells to their binding partners on T cells: peptide:MHC complex
TCR
peptide:MHC complex bind
TCR
TCR stimulation was shown to affect ICAM-1 (integrin ligand) binding to LFA-1 (integrin) on T cells. To demonstrate this, varying concentrations of purified ICAM-1 were added to unstimulated or TCR-stimulated T cells, and the amount of ICAM-1 binding was measured. The data from such an experiment are displayed on Figure Q7.28. Assign the red or blue lines correctly to 'unstimulated' or 'TCR-stimulated' T cells, and explain the reasoning for your answer.
TCR stimulation allows T cells to bind ligand with a higher affinity. This means less ligand is required for maximum binding. This means that TCR stimulated cells are the red line (solid) and unstimulated are the blue (dashed) line.
B cells that originally express IgM can be induced to produceIgA. In an individual, the signals to switch from IgM to IgA production is provided by
TFH cells in the germinal center
In cell culture experiments, purified B cells expressing IgM can be induced to switch to producing IgE by stimulating them with an antibody to CD40 (a stimulatory antibody) plus the cytokine IL-4. In an individual undergoing an immune response, these signals would normally be provided by:
TFH cells in the germinal center
Which of the following statements is correct regarding CD4 T cell differentiation
TGF-beta in the absence of IL-6 induce expression of Foxp3, which marks differentiation of Treg cells
All TLRs contain an exterior region with LRR domains that facilitate PAMP binding and interior region containing ___________ domains that bind adapter proteins and initiate intracellular signaling
TIR
West Nile Virus produces double stranded RNA as a replicative intermediate. Which Toll-like receptor would recognize WNV infection?
TLR3
Septic shock is a serious, often fatal response to an infection in the bloodstream. This response can be elicited in mice by intravenous injection of bacterial LPS. However, it was found that one strain of mice, C3H/HeJ, is resistant to LPS-induced shock. This fact was used to clone the gene for TLR-4 based on positional cloning from C3H/HeJ mice. Another example of a strain of mice that is resistant to LPS-induced septic shock is:
TNF-receptor-deficient mice
Septic shock is a serious, often fatal response to an infection in the bloodstream. This response can be elicited in mice by intravenous injection of bacterial LPS. However, it was found that one strain of mice, C3H/HeJ, is resistant to LPS-induced shock. This fact was used to clone the gene for TLR-4 based on positional cloning from C3H/HeJ mice. Another example of a strain of mice that is resistant to LPS-induced septic shock is:
TNFα-receptor-deficient mice
After production, naïve lymphocytes travel briefly through the blood to the spleen, peripheral lymph nodes, MALT
TRUE
Dendritic cells so important in adaptive immune responses because: Dendritic cells engulf, process and then transport antigens to a nearby secondary lymphoid tissue, such as lymph nodes, where they then encounter antigen-specific T cells, which then differentiate into effector T cells. Effector T cells are then able to leave the secondary lymphoid tissue and travel to the site of infection and perform their particular effector response to eradicate the infection
TRUE
Several pathogens produce proteins, either membrane-bound or secreted, that inactivate C3b that might be deposited on the pathogen surface. C3b is specifically targeted due to its central position in all three complement pathways.
TRUE
The DNA rearrangement of immunoglobulin genes is important for generating diversity of lymphocyte antigen receptors in order to mount responses to a wide range of infectious microorganisms. However, it may also lead to the development of B-cell cancer
TRUE
The immune response is different for bacteria, viruses, fungi and parasites.
TRUE
The inflammatory response is characterized by four classic symptoms: heat, redness, pain, and swelling. In some instances, this response can be triggered by stimuli that are non-infectious such as asbestos, a process known as 'sterile inflammation.' When exposure to the stimulating trigger is persistent, a state of chronic inflammation can result. This process is likely to be detrimental to the health of the host.
TRUE
True/False: Each family of NK cell receptors has members that promote NK cell activation, and members that send inhibitory signals when engaged. The difference between activating and inhibitory receptors lies in their association with accessory proteins that promote downstream signaling, or in their ability to recruit and activate inhibitory phosphatases, respectively.
TRUE
True/False: The extravasation of neutrophils into tissues at sites of infection or inflammation requires changes to both the endothelium and to the neutrophil that are induced by chemokines and cytokines produced in the infected tissue.
TRUE
True/False: The inflammatory response is characterized by four classic symptoms: heat, redness, pain, and swelling. In some instances, this response can be triggered by stimuli that are non-infectious such as asbestos, a process known as 'sterile inflammation.'When exposure to the stimulating trigger is persistent, a state of chronic inflammation can result. This process is likely to be detrimental to the health of the host.
TRUE
True/False: For cells of the innate immune system, each individual cell has multiple pattern recognition receptors, and can recognize many different pathogens. In contrast, cells of the adaptive immune system each express only a single antigen receptor, and have a single specificity for pathogen recognition.
TRUE
True/False: In the absence of an infection, most granulocytes (neutrophils, eosinophils, basophils) are found circulating in the blood, whereas other subsets of myeloid cells reside in tissues.
TRUE
True/False: Innate lymphoid cells and NK cells are effector cells that respond rapidly after encountering a pathogen. Several different subsets of innate lymphoid cells exist, and each is specialized to respond to a category of pathogen (e.g., viruses, extracellular bacteria, helminthic parasites, etc). Innate lymphoid cells reside primarily in tissues such as the lungs, the lining of the gastrointestinal tract, and the skin, because these sites represent the major routes of entry of pathogens into the body.
TRUE
True/False: Neutrophils regulate the production of active cathelicidins (a class of antimicrobial peptides) by segregating the inactive propeptide from the processing enzyme that cleaves and activates it in two different types of cytoplasmic granules. These two types of granules are induced to fuse with phagosomes after ingestion of microbes, bringing the processing enzyme and the propeptide together.
TRUE
True/False: One factor that contributes to the enhanced secondary response to an antigen is the increased number of antigen-specific lymphocytes present after the primary response; these are known as memory cells.
TRUE
True/False: TH1, TH2, TH17, and T follicular helper (TFH) cells represent four different subsets of CD4 effector cells. Each of these subsets produces a distinct set of cytokines when stimulated, that in turn, act to mobilize distinct immune effector mechanisms. While TH1, TH2, and TH17 cells recruit and activate innate immune cells, TFH cells act to amplify the adaptive immune response.
TRUE
True/False: The C3 convertase of the alternative complement pathway amplifies the overall magnitude of complement activation regardless of which of the three pathways initiated the complement activation initially.
TRUE
True/False: The spleen is a secondary lymphoid organ that performs several functions. In addition to its role as a site for initiating adaptive immune responses, the spleen is important in removing dead or damaged red blood cells from the circulation. Its immune function is important because blood-borne pathogens will not be transported to draining lymph nodes via the lymph fluid.
TRUE
What are the two major goals of T lymphocyte development? The two major goals of T lymphocyte development are (1) to ensure that all T cells have functional TCR and that (2) autoreactive cells are deleted (self-tolerance in ensured).
TRUE
Unlike innate immune responses, adaptive immune responses are initiated in secondary lymphoid organs. However, the innate immune response to an infection in a tissue has a pivotal role in inducing T-cell responses in the nearest lymph node by activating tissue dendritic cells and inducing their migration to the lymph node.
TRUE NOTE: Dendritic cells can be activated via their TLRs and other pathogen-recognition receptors, by tissue damage, or by cytokines produced during the inflammatory response. Activated dendritic cells migrate to the lymph node and express the co-stimulatory molecules that are required, in addition to antigen, for the activation of naive T cells. In the lymphoid tissues, these dendritic cells present antigen to naive T lymphocytes and prime antigen-specific T cells to divide and mature into effector cells that reenter the circulation.
The generation of optimal CD8 T cell memory following a primary infection requires CD4 T cell help for the responding CD8 T cells. This requirement for CD4 T cell help would not be completely replaced by supplying high levels of the cytokine IL-2 during the primary CD8 T cell response.
TRUE NOTE: The mechanism underlying the requirement for CD4 T cells is not completely understood. It may involve two types of signals received by the CD8 T cell, those received through CD40 and those received through the IL-2 receptor. CD8 T cells that do not express CD40 are unable to generate memory T cells. Although many cells could potentially express the CD40 ligand needed to stimulate CD40, it is most likely that CD4 T cells are the source of this signal. Therefore, in addition to providing the cytokine IL-2, CD4 T cells must interact with the responding CD8 T cells to provide CD40 ligand stimulation of CD40 on the CD8 T cells.
Based upon cytokine stimulation, CD4 T cells can differentiate into all of the following cell types except
Tc
Antibodies that bind with high affinity to some viral surface proteins require heavy chain variable complementary determining regions of unusual length. Whereas the average human heavy chain CDR length is 15 amino acids, antibodies with Vh CDR loops of >30 amino acids are readily detected in the repertoire. These antibody heavy chains with CDR lengths of >30 amino acids would likely be missing in individuals lacking
TdT
N nucleotide addition requires which of the following enzymes
TdT
Non-template addition of N-nucleotides
TdT
Which protein-encoding genes, although present in the germline DNA, are uniquely expressed by lymphocytes
TdT
Antibodies that bind with high affinity to some viral surface proteins require heavy chain CDR3 loops of unusual length. Whereas the average human heavy chain CDR3 length is ~15 amino acids, antibodies with VHCDR3 loops of >30 amino acids are readily detected in the repertoire. Which enzyme is responsible for these unusually long CDR3 loops?
TdT (terminal deoxynucleotidyl transferase)
Hosts utilize a variety of barriers to prevent pathogens from invading the body. Which of the following is a mechanical barrier used by the eyes/nasal cavity to protect a host from pathogens?
Tears
Antibodies that bind with high affinity to some viral surface proteins require heavy chain CDR3 loops of unusual length. Whereas the average human heavy chain CDR3 length is ~15 amino acids, antibodies with VHCDR3 loops of >30 amino acids are readily detected in the repertoire. Which enzyme is responsible for these unusually long CDR3 loops?
Terminal deoxynucleotidyl transferase (TdT)
Activated dendritic cells present antigen to naive T cells and also influence the differentiation of the T cell based on the cytokines the DC is secreting. Antigen recognition in conjugation with IL-4 secretion leads to differentiation of which Th subset
Th2
What happens when C3 CONVERTASE is generated?
The C3 convertase is bound covalently to the pathogen sur- face, where it cleaves C3 to generate large amounts of C3b, the main effector molecule of the complement system; and C3a, a small peptide that binds to specific receptors and helps induce inflammation.
The alternative pathway of complement activation has an important role in innate immunity, due to its ability to greatly amplify the amount of C3b deposited onto the pathogen surface. This amplification occurs because
The C3 convertase of the alternative pathway contains C3b, and can generate more of itself
The alternative pathway of complement activation has an important role in innate immunity, due to its ability to greatly amplify the amount of C3b deposited onto the pathogen surface. This amplification occurs because:
The C3 convertase of the alternative pathway contains C3b, and can generate more of itself
The alternative pathway of complement activation has an important role in innate immunity, due to its ability to greatly amplify the amount of C3b deposited onto the pathogen surface. This amplification occurs because:
The C3 convertase of the alternative pathway contains C3b, and can generate more of itself.
The alternative pathway of complement activation has an important role in innate immunity, due to its ability to greatly amplify the amount of C3b deposited onto the pathogen surface. This amplification occurs because:
The C3 convertase of the alternative pathway contains C3b, and can generate more of itself. The C3 convertase (C3bBb) of the alternative pathway contains C3b, allowing it to generate more of itself and amplify the overall level of C3b formed. Once additional molecules of C3b are made by C3bBb, these can recruit additional molecules of factor B and the plasma protease factor D. Factor D cleaves factor B, and one of the products, Bb, remains associated with C3b, forming more active C3 convertase.
How is C5 CONVERTASE formed by the ALTERNATIVE PATHWAY?
The C5 convertase of the alternative pathway is formed by the binding of C3b to the C3bBb convertase to form C3b Bb.
Inbred strains of mice often generate highly polarized CD4 T cell responses to specific infections that are dominated by one subset of effector cells. In the case of Balb/c mice infected with the intracellular protozoan Leishmania major, a robust CD4 T cell response is elicited, generating large numbers of L. major-specific T cells; however, this response does not eliminate the pathogen, and instead the mice succumb to the infection. One likely explanation for this finding is:
The CD4 T cell response produces effector cytokines that do not activate macrophages.
(BONUS) The addition and subtraction of nucleotides at the junctions between V, D, and J gene segments creates antibody proteins with wide variations in the numbers of amino acids in their CDR3 regions. This variability in CDR3 length is important as:
The CDR3 region is more important in binding antigen than the CDR1 and CDR2 regions are
Describe the Complement System?
The Complement System directly kills some microorganisms and interacts with others to promote their removal by phagocytic cells.
What is the Complement System?
The Complement System is a system of plasma proteins that targets pathogens both for lysis and for phagocytosis by cells of the innate immune system such as macrophages.
Fc-receptor molecules tend to have short cytoplasmic tails. How does this influence signaling events within the Fc-receptor cell?
The Fc receptor is dependent upon a co-receptor (e.g., containing ITAM or ITIM) that will trigger signaling events within the cell
Describe what PRIMARY GRANULES are?
The PRIMARY GRANULES of neutrophils are specialized membrane enclosed vesicles, rather similar to lysosomes, that contain a number of other antimicrobial agents as well as defensins
The antibody surface involved in antigen binding varies depending on the size and nature of the antigen. This surface can be concave or flat, and sometimes, can have extended protrusions. This is accomplished by:
The ability of different CDR sequences to form many structurally distinct shapes and surfaces
The antibody surface involved in antigen binding varies depending on the size and nature of the antigen. This surface can be concave or flat, and sometimes, can have extended protrusions. This is accomplished by:
The ability of different CDR sequences to form many structurally distinct shapes and surfaces.
One strategy for vaccine development currently under investigation is the use of pathogen-derived T cell epitopes as a component of the vaccine. For viral pathogens, implementing this strategy involves scanning the predicted amino acid sequences of the viral proteins for likely peptide epitopes that would bind to MHC class I and MHC class II molecules. In addition to the complication of MHC sequence polymorphism in the human population, another complication of this strategy for peptide epitopes that would bind to MHC class II proteins is:
The absence of defined sequence motifs that predict peptide binding to MHC class II molecules.
Signaling through the Drosophila Toll pathway is initiated when pathogen recognition receptors (PRRs) bind to microbial products, such as bacterial peptidoglycan. Aspects of this pathway share similarity to the mammalian complement cascade as well as to the innate recognition system based on TLRs. One feature of Toll signaling that resembles the complement pathway is:
The activation of an extracellular proteolytic cascade involving cleavage of self-proteins
Cytokine receptors of the hematopoietin superfamily engage signaling pathways that begin with JAK kinases and lead to activation of STAT-family transcription factors. Each receptor subunit in this superfamily binds a specific JAK kinase (one of four members) and each receptor complex usually activates one major STAT homodimer (one of seven). The specificity for activation of one STAT homodimer by each cytokine is determined by:
The amino acid sequence surrounding the phosphorylated tyrosine on each cytokine receptor subunit's cytoplasmic tail
How do anatomical barriers help against infection?
The anatomic barriers are fixed defenses against infection and consist of the epithelia that line the internal and external surfaces of the body along with the phagocytes residing beneath all epithelial surfaces. These phagocytes act directly by engulfing and digesting invading microorganisms
Describe the anatomic barriers found in the innate immune system?
The anatomic barriers are fixed defenses against infection and consist of: 1. The epithelia that line the internal and external surfaces of the body, along with the phagocytes residing beneath all epithelial surfaces.
Women with urinary tract infections caused by E. coli are generally treated with a course of antibiotics. A common complication of the antibiotic treatment is the occurrence of a vaginal yeast infection caused by Candida albicans, an organism that is normally present in very low numbers in the human vaginal tract. This complication occurs because:
The antibiotics kill many of the commensal organisms in the reproductive tract, allowing overgrowth of the pathogenic microbes.
Women with urinary tract infections caused by E.coli are generally treated with a course of antibiotics. A common complication of antibiotic treatment is the occurrence of a vaginal yeast infection caused by Candida albicans , an organism that is normally present in very low numbers in the human vaginal tract. This complication occurs because:
The antibiotics kill many of the commensal organisms in the reproductive tract, allowing overgrowth of the fungus
1.16 Short answer: The antibody protein is often depicted as an uppercase letter Y, with the two variable regions (antigen-binding domains) pointing up, and the stem consisting of the Fc region (constant domain). An analogy has been made between an antibody protein and a guided missile, with one type of antibody domain functioning as the guidance system, and the other type of domain as the 'payload.' Which antibody domain serves as the guidance system, and which as the payload? Explain your answer.
The antibody variable domains form the antigen-binding sites on the protein, and these serve as the guidance system. The specificity of these domains determines where the antibody protein binds, for instance, directly on a pathogen, or on a protein such as a toxin, or on a cell, etc. Antibody binding alone has limited effects. In order for antibodies to function in pathogen or toxin elimination, the antibody uses its Fc region, which functions as the 'payload.' This Fc region can be recognized by receptors on phagocytic cells, aiding in pathogen/toxin uptake, or it can promote complement activation on the pathogen. Without the 'payload,' antibody proteins would merely be binding molecules, with no other effector functions.
The antibody protein is often depicted as an uppercase letter Y, with the two variable regions (antigen-binding domains) pointing up, and the stem consisting of the Fc region (constant domain). An analogy has been made between an antibody protein and a guided missile, with one type of antibody domain functioning as the guidance system, and the other type of domain as the 'payload.' Which antibody domain serves as the guidance system, and which as the payload? Explain your answer.
The antibody variable domains form the antigen-binding sites on the protein, and these serve as the guidance system. The specificity of these domains determines where the antibody protein binds, for instance, directly on a pathogen, or on a protein such as a toxin, or on a cell, etc. Antibody binding alone has limited effects. In order for antibodies to function in pathogen or toxin elimination, the antibody uses its Fc region, which functions as the 'payload.' This Fc region can be recognized by receptors on phagocytic cells, aiding in pathogen/toxin uptake, or it can promote complement activation on the pathogen. Without the 'payload,' antibody proteins would merely be binding molecules, with no other effector functions.
Stimulation of the nucleic acid sensing TLRs that reside in endosomal membranes induces the production of a different cytokine response than is produced by stimulation of the plasma membrane TLRs. In part, this distinction is based on the different adapter proteins used by the nucleic acid sensing TLRs, leading to the activation of IRF factors. The cytokine response following stimulation of nucleic acid-sensing TLRs is characterized by production of:
The antiviral cytokine, type I interferon
Please list the cellular and humoral factors involved in the killing of a) viruses and intracellular bacteria, b) extracellular bacteria, and c) parasites. Explain their role and functions in 1-2 sentences (14/20 points)
The cellular factor involved in killing viruses and intracellular bacteria is the use of cytotoxic T lymocytes using T cell receptor activation, which kills off the infected cells. The humoral factor involved in killing viruses and intracellular bacteria is neutralization which helps block the entry of these viruses and bacteria. b) The cellular factors involved in killing extracellular bacteria is the use of Granzyme and Perforin-mediate cytolysis, which is capable of breaking open the baterial cell wall and memebrane, killing off the bacteria. The humoral factor involved in killing extracellular bacteria is opsonization and phagocytosis because the anitbodies bind to the extracellular bacteria to be engulfed later on. c) The cellular factors involved in killing parasites are cytokines activated macropahges that are brought to the parasite, and the parasite is killed off an absorbed. The humoral factors involved in killing parasites is complement activation because of the creation of the memebrane attack complex, which will destroy the plasma membranes of the parasite.
Naive T cells are isolated and left untreated or treated with 'compound X' for 1 hour. Following this, the T cells are incubated with a range of concentrations of a soluble form of ICAM-1 that has been conjugated to a fluorescent dye (soluble-ICAM-1-FITC). Fifteen minutes later, the cells are washed, and the relative amount of fluorescence bound to the cells is measured. The results of this assay are shown in the figure below. Based on this data, the most likely identity of Compound X is _________________.
The chemokine ligand for CCR7 NOTE: Yes. Signaling through chemokine receptor CCR7 on naive T cells induces LFA-1 to change conformation to the high-affinity state. This greatly increases its affinity for integrin binding. Therefore, after treatment with the ligand for CCR7 (which is CCL21), naive T cells would show maximal binding to ICAM-1 at a lower concentration of soluble-ICAM-1 than the untreated cells.
How is the CLASSICAL PATHWAY of the COMPLEMENT SYSTEM initiated
The classical pathway (top center) is triggered by binding of C1 either to the pathogen surface or to antibody bound to the pathogen.
How are the cleavage products of the ALTERNATIVE PATHWAY designated?
The cleavage products of the ALTERNATIVE PATHWAY are also designated by the addition of lowercase a and b. Thus, the large fragment of B is called Bb and the small fragment Ba.
How are COMPLEMENT PATHWAYS triggered?
The complement pathways are triggered by proteins that act as pattern recognition receptors to detect the presence of pathogens. This detection activates an initial zymogen, triggering a cascade of proteolysis in which complement zymogens are activated sequentially, each becoming an active enzymes that cleaves and activates many molecules of the next zymogen in the pathway, amplifying the signal as the cascade proceeds.
What is COMPLEMENT SYSTEM composed of and where are they produced?
The complement system is composed of more than 30 different plasma proteins, which are produced mainly by the liver.
How does the COMPLEMENT SYSTEM recognize microbes and then mark them for destruction?
The complement system recognizes features of microbial surfaces and marks them for destruction by coating them with C3b.
When a pathogen breaches the host's epithelial barriers and initial antimicrobial defenses, it next encounters a major component of innate immunity known as...
The complement system, or complement.
Antibody diversity is generated by multiple mechanisms, each of which contributes to the generation of antibodies with up to 1011 different amino acid sequences in their antigen-binding sites. Several of these mechanisms involve changes in the DNA sequences encoding the antibody heavy and light chain proteins. One mechanism that does not rely on changes to the DNA within the immunoglobulin heavy and light chain gene loci is, instead, dependent on:
The contributions of amino acids from both the heavy chain and the light chain to form the antigen-binding site
All of the following statements regarding Toll-like receptors are true except _____. The cytoplasmic signaling domain contains regions specialized in detecting PAMPs. They sense molecules not found in or on human cells. They facilitate changes in gene expression. The extracellular domain detects the microbial component. They form either transmembrane homodimers or heterodimers
The cytoplasmic signaling domain contains regions specialized in detecting PAMPs.
An infant with recurrent bacterial and fungal infections is suspected to have an immunodeficiency disease. Within two days after exposure to a pathogen, the organisms have proliferated to dangerous levels requiring immediate systemic antibiotic treatment. It is unlikely that this infant has a defect in B or T lymphocyte responses to the infection because:
The defective immune response occurs too rapidly following infection to be due to a defect in B or T lymphocytes responses
An infant with recurrent bacterial and fungal infections is suspected to have an immunodeficiency disease. Within two days after exposure to a pathogen, the organisms have proliferated to dangerous levels requiring immediate systemic antibiotic treatment. It is unlikely that this infant has a defect in B or T lymphocyte responses to the infection because:
The defective immune response occurs too rapidly following infection to be due to a defect in B or T lymphocytes responses.
An infant with recurrent bacterial and fungal infections is suspected to have an immunodeficiency disease. Within two days after exposure to a pathogen, the organisms have proliferated to dangerous levels requiring immediate systemic antibiotic treatment. It is unlikely that this infant has a defect in B or T lymphocyte responses to the infection because: A.Bacteria and fungi do not require B cell or T cell responses for their clearance. B.Bacteria and fungi are not efficiently transported to draining lymph nodes to initiate adaptive immune responses. C.Systemic infections of bacteria and fungi are usually cleared by the spleen. D.The defective immune response occurs too rapidly following infection to be due to a defect in B or T lymphocytes responses. E.Adaptive immune responses require dendritic cells to take up and degrade pathogens.
The defective immune response occurs too rapidly following infection to be due to a defect in B or T lymphocytes responses.
An infant with recurrent bacterial and fungal infections is suspected to have an immunodeficiency disease. Within two days after exposure to a pathogen, the organism have proliferated to dangerous levels requiring immediate systemic antibiotic treatment. It is unlikely that this infant has a defect in B or T lymphocytes responses to the infection because
The detective immune response occurs too rapidly following infection to be due to a defect in B or T lymphocytes responses
Several subsets of innate lymphoid cells (ILCs) have been identified that share their patterns of cytokine production with the known subsets of T cells. The combined activity of related ILC and T cell subsets is effective in eradicating pathogenic infections because:
The early response of ILCs that reside at the site of infection is followed by the later more robust response of pathogen-specific T cells that migrate to the site of infection.
Inherited immunodeficiency diseases result from a single gene defect in one component of the immune system. By identifying the class of microbial pathogens a given immunodeficient individual becomes susceptible to, studies of these disease indicate
The essential immune mechanism required for resistance to each category of pathogen
Inherited immunodeficiency diseases result from a single gene defect in one component of the immune system. By identifying the class of microbial pathogens a given immunodeficient individual becomes susceptible to, studies of these diseases indicate:
The essential immune mechanism required for resistance to each category of pathogen
The importance of complement activation as an innate immune defense against infections is illustrated by
The evolution of complement avoidance strategies by many pathogens
The importance of complement activation as an innate immune defense against infections is illustrated by:
The evolution of complement avoidance strategies by many pathogens
Cytotoxic T cells are rapid killers of infected target cells. Within minutes of the interaction of a cytotoxic T cell with a target cell, the program of apoptosis in the target cell is initiated. This rapid activity is a consequence of
The expression and packaging of perforin and granzymes in cytotoxic granules prior to target cell encounter
Cytotoxic T cells are rapid killers of infected target cells. Within minutes of the interaction of a cytotoxic T cell with a target cell, the program of apoptosis in the target cell is initiated. This rapid activity is a consequence of:
The expression and packaging of perforin and granzymes in cytotoxic granules prior to target cell encounter
Cytotoxic T cells are rapid killers of infected target cells. Within minutes of the interaction of a cytotoxic T cell with a target cell, the program of apoptosis in the target cell is initiated. This rapid activity is a consequence of:
The expression and packaging of perforin and granzymes in cytotoxic granules prior to target cell encounter NOTE: Yes. Cytotoxic T cells can kill their targets rapidly because they store preformed cytotoxic proteins in forms that are inactive in the environment of the cytotoxic granule.
One surprising aspect of the immune system is that individuals make responses to human tissues from a different individual, causing serious problem for organ and tissue transplantation. The basis for this immune response is:
The extensive polymorphism of MHC genes in the human population
One surprising aspect of the immune system is that individuals make responses to human tissues from a different individual, causing serious problems for organ and tissue transplantation. The basis for this immune response is:
The extensive polymorphism of MHC genes in the human population
One surprising aspect of the immune system is that individuals make responses to human tissues from a different individual, causing serious problems for organ and tissue transplantation. The basis for this immune response is:
The extensive polymorphism of MHC genes in the human population.
Our environment contains masses of microorganisms, many of which reside as commensal organisms on our body's mucosal and epithelial surfaces without causing disease. What two features distinguish a pathogenic microbe from these commensal microbes?
The first important feature of a pathogenic microbe is that it must establish a replicating colony of organisms in our body. This can occur by the pathogen crossing an epithelial barrier and replicating in the tissue, or by attaching to the epithelial surface and establishing a colony there. The second feature is that the pathogen needs to have special mechanisms to evade the innate immune response.
The response to an initial infection occurs in three phases. What are they?
The first two phases rely on the recognition of pathogens by germline-encoded receptors of the innate immune system. Where as the third phase, incorporates the adaptive immunity's variable antigen-specific receptors that are produced as a result of gene segment rearrangements.
How are the glycan of a yeast surface protein different than that the glycan of a vertebrate cell?
The glycans of yeast surface proteins commonly terminate in mannose residues rather than the sialic acid residues (N-acetylneuraminic acid) that terminate the glycans of vertebrate cells These difference are how the LECTIN PATHWAYS recognize these pathogens.
What happens if the immediate defense of the innate immune system fail?
The innate immune cells become activated by pattern recognition receptors (PRRs) that detect molecules called pathogen-associated molecular patterns (PAMPs) (see Section 1-5) that are typical of microbes. The activated innate cells can engage various effector mechanisms to eliminate the infection.
how is the innate immune system able to detect infections and distinguish between pathogens and host tissues?
The innate immune system uses a limited number of secreted proteins and cell-associated receptors to detect infections and to distinguish between pathogens and host tissues.
In the cases of some infections, such as mice infected with adenovirus, the generation of effector cytotoxic CD8 T cell responses needed to clear the infection is dependent on the antigen-presenting dendritic cells receiving stimulation through the CD40 receptor on their surface, a process known as dendritic cell 'licensing'. In this infection system, the dendritic cell would likely receive CD40 receptor stimulation from:
The interaction with a CD4 effector cell expressing CD40 ligand
What is the MUCOSAL EPITHELIA?
The internal epithelia are known as mucosal epithelia because they secrete a viscous fluid called mucus, which contains many glycoproteins called mucins.
What is the key feature of C3b?
The key feature of C3b is its ability to form a covalent bond with microbial surfaces, which allows the innate recognition of microbes to be translated into effector responses.
How is the LECTIN PATHWAY of the COMPLEMENT SYSTEM initiated?
The lectin pathway is initiated by soluble carbohydrate binding proteins -mannose-binding lectin (MBL) and the ficolins—that bind to particular carbohydrate structures on microbial surfaces. Specific proteases, called MBL-associated serine proteases (MASPs), that associate with these recognition proteins then trigger the cleavage of complement proteins and activation of the pathway
he terminal components of the complement pathway assemble to form a membrane attack complex that can induce pathogen lysis and death. Yet, evidence indicates that this feature of complement is less important than the earlier steps that promote pathogen opsonization and induce inflammation. This conclusion is based on:
The limited susceptibility to infections of patients with deficiencies in terminal complement components Patients with genetic deficiencies in terminal complement components show only a limited increase in susceptibility to infection. These individuals are more susceptible to infection by Neisseria species that cause gonorrhea or meningitis. Otherwise, these individuals show no other increased susceptibility to infection, indicating that formation of the membrane attack complex is a less important aspect of complement activation compared to the earlier steps that lead to opsonization of the pathogen as well as inducing inflammation.
Dendritic cells in the skin, known as Langerhans cells, express very high levels of the NOD-like receptor, NLRP3. Previous studies showed that treatment of these cells with the Staphylococcus aureus pore-forming toxin causes K+ efflux from the cells. To investigate whether this signal could induce IL-1 (an inflammatory cytokine) secretion by the cells, the following study (Figure Q3.16) was performed:
The live S. aureus bacteria activate a TLR and NLRP3.
The final stages of T cell development occur in the thymic medulla, after the developing cells become CD4 or CD8 single-positive. One important change that occurs during this final maturation is:
The loss of susceptibility to T-cell receptor-induced apoptosis
1.23 Short answer: Dendritic cells, also called 'antigen-presenting-cells' are considered the bridge between the innate and the adaptive immune responses. Describe two key features of dendritic cells that are essential for them to provide this bridging function.
The most relevant features of dendritic cells in this context are: 1. Dendritic cells respond to infections using innate pattern recognition receptors (PRRs) that recognize PAMPs. 2. Once triggered by PRR stimulation, dendritic cells are induced to migrate from the infected tissue to the regional draining lymph node. 3. Following stimulation of the PRRs on a dendritic cell, dendritic cells up-regulate co-stimulatory molecules that are required to activate T lymphocytes. 4. Following pathogen uptake by the dendritic cell, the pathogen is degraded and peptides of the pathogen are displayed on the dendritic cell surface for recognition by the antigen receptors on T lymphocytes.
Dendritic cells, also called 'antigen-presenting-cells' are considered the bridge between the innate and the adaptive immune responses. Describe two key features of dendritic cells that are essential for them to provide this bridging function.
The most relevant features of dendritic cells in this context are: 1. Dendritic cells respond to infections using innate pattern recognition receptors (PRRs) that recognize PAMPs. 2. Once triggered by PRR stimulation, dendritic cells are induced to migrate from the infected tissue to the regional draining lymph node. 3. Following stimulation of the PRRs on a dendritic cell, dendritic cells up-regulate co-stimulatory molecules that are required to activate T lymphocytes. 4. Following pathogen uptake by the dendritic cell, the pathogen is degraded and peptides of the pathogen are displayed on the dendritic cell surface for recognition by the antigen receptors on T lymphocytes.
Given the enormous heterogeneity of antigen receptors expressed on the populations of naive B and T lymphocytes, the adaptive immune response relies on a process where a rare lymphocyte binds to antigen and is first induced to proliferate, before it can perform its effector function. For B cells, there is a mechanism that ensures that the specificity of the antibody secreted by the plasma cell will recognize the same pathogen that initially stimulated the B cell antigen receptor and induced B cell proliferation. Which of the following best describes that mechanism?
The naive B cell expresses a membrane-bound form of the antibody as a receptor, and secretes that same antibody when it differentiates into a plasma cell.
What happens after C3b coats pathogens?
The next step in the complement cascade is the generation of the C5 convertases.
Lymphocyte activation leads to robust proliferation and effector cell differentiation. The metabolic demands of these processes are met, in part, by up-regulation of glycolytic enzymes and nutrient transporters on the activated cell membrane. A key intermediate in the signaling pathway leading to enhanced glucose metabolism following antigen receptor stimulation is:
The phosphoinositide, PIP3
c) Following an infection, how does the population of innate cells change? Starting with the cartoon representing your answer to part (a), draw the population present at one week post-infection.
The population of innate cells is largely unchanged before and after infection.
A mouse is immunized with a single 9 amino acid peptide derived from the influenza virus. This peptide binds to MHC class I and produces an epitope (peptide:MHC complex) recognized by a small number of naive CD8 T cells in the mouse. The peptide is mixed with CpG oligonucleotides that are ligands for TLR-9. Surprisingly, this immunization regimen generates a very poor cytotoxic CD8 effector response to targets coated with this peptide compared to immunization with a preparation of intact heat-killed influenza virus mixed with CpG oligonucleotides. The enhanced cytotoxic T cell response to the peptide observed following immunization with intact viral particles compared to the peptide alone is due to:
The presence of CD4 T cell epitopes in the intact virus
Some Pattern Recognition Receptors (PRRs) recognize nucleic acids, like RNA or DNA. Since our own cells contain human RNA and DNA, the activation of innate immune pathways by these PRRs must rely on additional criteria to discriminate self from nonself. Additional criteria include everything EXCEPT:
The presence of adenosine residues in viral RNA
Individuals with peanut allergies can exhibit a variety of symptoms following exposure to the peanut allergen. These symptoms can include a runny nose, skin reactions such as hives, itching in the mouth and throat, digestive problems such as cramps, diarrhea or vomiting, and shortness of breath or wheezing. This variety of symptoms is a result of:
The presence of mast cells with pre-bound IgE in all mucosal tissues
Unlike somatic hypermutation, class switching occurs in discrete sequence regions upstream of the immunoglobulin heavy chain coding sequences (called switch regions). One key element in directing the enzyme AID to a specific switch region is the opening of the DNA duplex combined with polymerase stalling during active transcription in that region. A second key feature of directing AID to a specific switch region is:
The processed RNA from the switch region guides AID to this site in the DNA
How are proteins of the ALTERNATIVE PATHWAY designated?
The proteins of the alternative pathway are designated by different capital letters, for example, factor B and factor D.
The formation of the C3 convertase is a key step in complement activation that occurs in all three complement pathways. This enzyme cleaves C3 in blood plasma, leading to a conformational change in the C3b fragment that exposes its reactive thioester group. The activated C3b is potentially harmful to the host, if it becomes covalently attached to a host cell, rather than to the surface of a pathogen. This deleterious outcome is largely avoided by:
The rapid hydrolysis of active C3b in solution, rendering it inactive
The formation of the C3 convertase is a key step in complement activation that occurs in all three complement pathways. This enzyme cleaves C3 in blood plasma, leading to a conformational change in the C3b fragment that exposes its reactive thioester group. The activated C3b is potentially harmful to the host, if it becomes covalently attached to a host cell, rather than to the surface of a pathogen. This deleterious outcome is largely avoided by:
The rapid hydrolysis of active C3b in solution, rendering it inactive.
The formation of the C3 convertase is a key step in complement activation that occurs in all three complement pathways. This enzyme cleaves C3 in blood plasma, leading to a conformational change in the C3b is potentially harmful to the host, if it becomes covalently attached to a host cell, rather than to the surface of a pathogen. This deleterious outcome is largely avoided by:
The rapid hydrolysis of active C3b in solution, rendering it inactive.
The formation of the C3 convertase is a key step in complement activation that occurs in all three complement pathways. This enzyme cleaves C3 in blood plasma, leading to a conformational change in the C3b fragment that exposes its reactive thioester group. The activated C3b is potentially harmful to the host, if it becomes covalently attached to a host cell, rather than to the surface of a pathogen. This deleterious outcome is largely avoided by:
The rapid hydrolysis of active C3b in solution, rendering it inactive. Active C3b is highly labile, and is rapidly inactivated by hydrolysis. This prevents the C3b from remaining active should it diffuse away from the pathogen surface where it was activated by the C3 convertase.
How does C1 activate the CLASSICAL PATHWAY?
The recognition function of C1 resides in the six globular heads of C1q. When two or more of these heads interact with a ligand, itcauses a conformational change in the C1r:C1s complex, which leads to the activation of C1r. Then activated Clr cleaves Cls to activate it. The activated C1s acts on the next two components of the classical pathway, C4 and C2. Specifically, C1s cleaves C4 to produce C4b, which binds covalently to the pathogen surface. Then C4b binds one molecule of C2, which is cleaved by C1s to produce C2a. This produces the active C3 convertase (C4b2a), which is the C3 convertase of both the lectin and the classical pathways.
The convertase of the lectin and classical pathways, C4b2a, and the convertase of the alternative pathway, C3bBb, initiate what?
The same subsequent events they cleave C3 to C3b and C3a.
In response to an intracellular bacterial or viral infection, effector TH1 cells, macrophages, NK cells, and CD8 cytotoxic effector cells are all recruited to the site of infection. The coordinated recruitment of all of these cell types is orchestrated by:
The shared expression of chemokine receptors on these different cell types
In response to intracellular bacterial or viral infection, effector TH1 cells, macrophages, NK cells, and CD8 cytotoxic effector cells are all recruited to the site of infection. The coordinated recruitment of all of these cell types is orchestrated by:
The shared expression of chemokine receptors on these different cell types
Lectin; classical;alternative
The three pathways leading to the activation of the complement are: 1. [n] pathway: Mannose binding lectin can be the key activator of this pathway 2. [o] pathway: Immunoglobulin can be the key activator of this pathway 3. [p] pathway: Spontaneous hydrolysis of C3 can be the key activator of this pathway
Cytotoxic effector T cells also produce inflammatory cytokines such as IFN-g and TNF-a when their T-cell receptor recognizes peptide:MHC on a target cell. One effect of this cytokine secretion is to enhance the ability of CD8 effector T cells to recognize and kill other infected cells in the nearby vicinity. This enhanced activity is due to:
The up-regulation of MHC class I protein expression by IFN-gamma.
An infant is admitted to the hospital with a history of recurrent and persistent bacterial infections. His physician suspects he has an immunodeficiency disease, and obtains a sample of the patient's peripheral blood. The white blood cells of the patient and a healthy infant are analyzed by antibody staining followed by flow cytometry, and the results are shown in Figure. Anti-CD3 antibodies bind TCR and its co-receptor while anti-CD19 antibodies recognize CD19 receptor on B cells. Please indicate which blood test belongs to the sick patient. What are cell populations shown by yellow, green and violet?
The yellow population represents receptors that activate both helper T cells and cytotoxic T cells. The green population represents normal blood cells that lack B cell lineage and T cell lineage. The violet population represents the normal population of B lineage cells The blood test with no violet cell population belongs to the sick patient because that means that the patient has no B cells at all in the blood because CD19 is expressed by all B cell lineage cells.
How do Antimicrobial Peptides work?
Their Cationic regions ( positively charged area) binds to negatively charged pathogen membrane.Once they are in membrane they form pores within membrane, which in turn allows for an opening in the cell wall making it leak. That in turn kills pathogens. The mechanism is thought to involve insertion of the hydrophobic region into the membrane bi-layer and the formation of a pore that makes the membrane leaky.
The immune system evolved to protect us against infections from pathogenic microorganisms. However, immune responses can also cause, rather than prevent disease. Give two examples of situations in which an immune response causes a disease, whereas the absence of a response has no consequences.
There are several cases in which immune responses can cause diseases, whereas their absence is a neutral event. 1) allergic responses to food items, antibiotics, metal ions, or inhaled substances. 2) autoimmune diseases, in which individuals make destructive immune responses to their own cells or tissues.
1.39 Short answer: The immune system evolved to protect us against infections from pathogenic microorganisms. However, immune responses can also cause, rather than prevent disease. Give two examples of situations in which an immune response causes a disease, whereas the absence of a response has no consequences.
There are several cases in which immune responses can cause diseases, whereas their absence is a neutral event. One example is allergic responses to non-threatening antigens, such as food items, antibiotics, metal ions, or inhaled substances. Another example is autoimmune diseases, in which individuals make destructive immune responses to their own cells or tissues. Graft rejection in transplant patients is another possible example, although it doesn't quite fit the criterion of being 'an immune response that causes disease,' since in this case, the immune response is prevented 'the cure' rather than causing the disease.
The process of somatic hypermutation of antibody V regions sequences is initiated by the enzyme AID. This enzyme targets cytidine residues in the DNA sequence that are normally part of a G:C pair in the double-stranded DNA. Yet the hypermutation process generates mutations at both G:C and A:T base pairs of the original sequence because:
There are two different repair pathways that have different outcomes, one targeting G:C and one targeting A:T base pairs.
What make the innate receptors of the innate immune system unique?
These are called innate receptors because they are inborn; they are encoded by genes directly inherited from an individual's parents, and do not need to be generated by the gene rearrangements used to assemble antigen receptors of lymphocytes .
How are the LECTIN AND CLASSICAL PATHWAYS of COMPLEMENT activated?
These pathways are initiated by proteins that bind to pathogen surfaces It is important that activating events are confined to this same site, so that C3 activation also occurs on the surface of the pathogen and not in the plasma or on host-cell surfaces. This is achieved principally by the covalent binding of C4b to the pathogen surface.
Besides providing a physical barrier to infection, what else does our surface epithelia do?
They also produce a wide variety of chemical substances that are microbicidal or that inhibit microbial growth. EX: the acid pH of the stomach and the digestive enzymes, bile salts, fatty acids, and lysolipids present in the upper gastrointestinal tract create a substantial chemical barrier to infection
How are Proteins that belong to the classical pathway designated?
They are designated by the letter C followed by a number.
Which of the following statements does NOT apply to MHC class I associated peptides?
They are generated by proteases in late endosomes
Which of the following statements does NOT apply to MHC class I associated peptides?
They are generated by proteases in late endosomes.
what are Lipopolysaccharides (LPS)?
They are large molecules consisting of a lipid and a polysaccharide composed of O-antigen. They are found in the outer membrane of Gram-negative bacteria, and elicit strong immune responses in animals.
What are COMMENSAL BACTERIA?
They are non-pathogenic bacteria that help keep pathogens at bay. .
How are α-defensins stored once they are made?
They are stored in the PRIMARY GRANULES of Neutrophils.
A mouse is immunized with the tetanus toxoid protein (inactivated toxin) in adjuvant. One week later, the entire population of splenic B cells are isolated from the mouse and mixed with tetanus toxoid-specific CD4 TFH cells plus the purified tetanus toxoid protein. Four days later, the total number of B cells in the culture and the number of tetanus toxoid-specific B cells are determined and compared to the starting population on the day of isolation. The results are shown in the figure below. The tetanus-specific B cells preferentially survive and proliferate because INSERT GRAPH PICTURE
They are the only B cells presenting the tetanus peptide to the TFH cells
Are C3 convertases C3bBb and C3(H2O) Bb short lived or long lived?
They are very short-lived.
How are short lived C3 convertases C3bBb and C3(H2O) Bb stabilized?
They are, stabilized by binding the plasma protein properdin (factor P). Which in turn enhances the effectiveness of the alternate pathway.
How do FICOLINS bind to pathogens?
They bind to fucose, and N-acetylglucosamine (GlcNAc) , but don't bind to mannose-containing carbohydrates.
Studies in mice have shown that resident memory cells (TRM) most often take up permanent residence in the tissue where the initial infection that produced those memory cells occurred. In this location, they are poised to respond rapidly should that infection re-occur in that same location. In contrast, central memory cells (TCM) are primarily found in secondary lymphoid organs, where they can be activated to proliferate and differentiate into effector cells when stimulated by antigen-bearing dendritic cells following re-infection. The third subset of memory cells, effector memory cells (TEM), are recirculating cells that can readily enter tissues at sites of inflammation or infection and are poised to rapidly respond to re-infection. The subset of TEM cells provides an important component of protective immunity to re-infection by the same pathogen because:
They can protect against re-infection that occurs in a different site in the body than the primary infection. NOTE: Yes. While re-infection with the same pathogen often occurs in the same location as the initial primary infection, this is not always the case. Therefore, the circulating effector memory T cells can patrol all tissues in the body, and are not restricted to a single tissue of residence.
What roles do MANNOSE BINDING LECTIN (MBL) and FICOLIN play when it comes to the LECTIN PATHWAY?
They can recognize some of the pathogen-specific carbohydrates that are unique to some pathogens Such as Mannose and Fucose residues found of pathogen surface.
Precursor CTLs are characterized by each of the following EXCEPT: they produce low amounts of IL-2. they lack cytotoxic activity. they express CD4. they do not express CD25. they do not divide.
They express CD4
What do these COMPLEMENT-REGULATORY PROTEINS interact with to protect host cells from being damaged by complement activation on their surfaces?
They interact with C3b and either prevent the convertase from forming or promote its rapid dissociation.
Most B and T lymphocytes in the circulation appear as small, inactive cells, with little cytoplasm, few cytoplasmic organelles, and nuclei containing condensed inactive chromatin. Yet these cells comprise the adaptive immune response, without which individuals die in infancy. What is the explanation for this apparent dichotomy?
They only activate when they encounter a recognized antigen
Mannose binding lectins (MBL) and ficolins are the two classes of proteins that can initiate the lectin pathway of complement activation. These proteins are selective for activating complement on the surfaces of microbial pathogens rather than host cells because:
They only bind to carbohydrate side chains and oligosaccharide modifications found on pathogen surfaces but not on host cell membranes.
Mannose binding lectins (MBL) and ficolins are the two classes of proteins that can initiate the lectin pathway of complement activation. These proteins are selective for activating complement on the surfaces of microbial pathogens rather than host cells because:
They only bind to carbohydrate side chains and oligosaccharide modifications found on pathogen surfaces but not on host cell membranes. MBL and ficolins have binding specificity for carbohydrate side chains and oligosaccharide modifications that are unique to microbial pathogens, and not found on host cells. MBL binds to mannose, fucose, and GlcNac residues, which are common on microbial glycans; in contrast, MBL does not bind to sialic residues, which terminate vertebrate glycans. Ficolins have specificity for binding to oligosaccharides containing acetylated sugars, a structure also only found on pathogen surfaces, not on host cells.
Experimental mouse models have been developed to study the mechanisms leading to the breakdown of self-tolerance and the onset of autoimmunity. One strategy is to express a foreign antigen, such as a viral protein, in a single defined cell type in a peripheral organ. For instance, the lymphocytic choriomeningitis virus (LCMV) glycoprotein has been expressed in β-islet cells of the pancreas by making a line of mice that is transgenic for a construct linking the LCMV-glycoprotein gene to the insulin promoter. In these transgenic mice, the LCMV protein is expressed only in pancreatic β-islet cells. Thymocytes with T-cell receptors specific for a peptide of LCMV-glycoprotein bound to MHC class I develop normally in the thymus, and do not undergo negative selection. The fate of these T cells once they emigrate from the thymus would likely be:
They would either be deleted in the periphery or would become unresponsive.
What happens after COMPLEMENT PATHWAYS are triggered?
This results in activation of three distinct effector pathways 1. Inflammation 2. phagocytosis 3. membrane attack that help eliminate the pathogen. In this way, the detection of even a small number of pathogens produces a rapid response that is greatly amplified at each step.
True or False: The acute phase response contributes to infection control by producing molecules that promote pathogen opsonization and complement activation. This response is only induced by direct action of microbial components on hepatocytes in the liver.
This statement is false
True or False: All cell surface Fc receptors bind antibodies with low affinities. In the absence of antigens, antibodies do not associate with cell surface Fc receptors.
This statement is false.
True or False: Diacylglycerol (DAG) is one of the two products generated when PLC-cleaves the membrane phospholipid, PIP2. This small lipid mediator remains associated with the plasma membrane and induce calcium entry into the cell.
This statement is false.
True or False: During B cell development, pre-B-cell receptors receive signals from self-antigens for the cells to survive and proliferate.
This statement is false.
True or False: In negative selection, B cells that interact weakly with self-antigens will either go anergic or enter a state of immunological ignorance. In both cases, the B cells are unresponsive to the antigens, so anergy and immunological ignorance are two names for the same phenomenon.
This statement is false.
True or False: Macrophages, neutrophils, and dendritic cells (DCs) are all phagocytes. Because of this, they can present pathogen-derived protein antigens to T cells. In this regard, they are antigen-presenting cells (APCs) as well.
This statement is false.
True or False: Naive T cells scan the dendritic cells in the cortical region of the lymph node as they migrate. The initial encounter of T cells with dendritic cells is mediated by interactions between the T-cell receptor and the peptide:MHC complexes on the dendritic cell.
This statement is false.
True or False: Naïve T cells scan the dendritic cells in the cortical region of the lymph node as they migrate. The initial encounter of T cells with dendritic cells is mediated by interactions between the T-cell receptor and the peptide:MHC complexes on the dendritic cell.
This statement is false.
True or False: T cell development in the thymus shares some similarities to a pipeline. As new progenitor cells enter the thymus, the most mature thymocytes are pushed out of the thymus to enter the circulation by a passive process.
This statement is false.
True or False: T cell receptor structure is much simpler than B cell receptor. TCR mimics the Fab region in a BCR. Therefore, TCR is completely made up of variable regions, unlike BCRs which have both variable and constant regions. A.This statement is true.
This statement is false.
True or False: The antibody protein has two functional domains, one for antigen binding and a second to confer specific effector functions. The former is encoded by the light chain and the latter the heavy chain.
This statement is false.
True or False: The antibody protein has two functional domains, one for antigen binding and a second to confer specific effector functions. These two functional domains are encoded by the antibody light chain and antibody heavy chain polypeptides, respectively.
This statement is false.
True or False: The generation of a complete coding sequence for an antibody heavy chain involves a process of DNA rearrangement that links V, D, and J gene segments together to form the exon that encodes the heavy chain V region. A similar type of DNA rearrangement is also utilized for the simultaneous expression of IgM and IgD antibodies by the same B cell.
This statement is false.
True or False: The mechanism by which CTLA-4 and PD-1 inhibit T cell activation is by recruiting inhibitory phosphatases SHP and SHIP to remove the phosphates from ITAMs.
This statement is false.
True or False: B-cell receptors and T-cell receptors share a mechanism for generating diversity, and also share structural homology in their V domains.
This statement is true.
True or False: CTLA-4 and PD-1 are both inhibitors of T cell activation but their mechanisms are different.
This statement is true.
True or False: Cytotoxic T cells that lack expression of perforin are more defective in killing target cells than those that lack granzymes.
This statement is true.
True or False: Each family of NK cell receptors has members that promote NK cell activation, and members that send inhibitory signals when engaged. The difference between activating and inhibitory receptors lies in their association with accessory proteins that promote downstream signaling, or in their ability to recruit and activate inhibitory phosphatases, respectively.
This statement is true.
True or False: In the majority of viral infection, CD8 T cell activation requires CD4 T cell help.
This statement is true.
True or False: Like TCR signaling, B cell receptor (BCR) signaling is initiated by a kinase phosphorylating tyrosine resides in ITAM motifs of BCR signaling subunits.
This statement is true.
True or False: The C3 convertase of the alternative complement pathway amplifies the overall magnitude of complement activation regardless of which of the three pathways initiated the complement activation initially.
This statement is true.
True or False: Unlike innate immune responses, adaptive immune responses are initiated in secondary lymphoid organs. However, the innate immune response to an infection in a tissue has a pivotal role in inducing T-cell responses in the nearest lymph node by activating tissue dendritic cells and inducing their migration to the lymph node
This statement is true.
anaphylatoxins; opsonin; MAC
Three important functions of the complement are: - production of [q]: fragment C5a and C3a lead to local inflammation - [r]: C3b is deposited to the surface of the pathogen - formation of the [s]: pore formation in the membrane of the pathogen
An individual with normal B cells, but an absence of T-cells might have a defect in:
Thymic stromal cells
Genetically inherited immunodeficiency diseases can result from defects in nearly any component of the immune response. The most severe forms of immunodeficiency occur when T cells are absent or non-functional. An individual with normal B cells, but an absence of T cells might have a defect in
Thymic stromal cells
The exon encoding the V region of an immunoglobulin protein is generated by a process of somatic recombination. This recombination event brings V gene and J gene segments together:
To generate maximum diversity in the CDR3 sequence of the V region
Follicular helper T cells are a recent discovery in the Helper T-cell lineage. What is the primary role of TFH cells?
To help B cell development in germinal centers
IgA is typically found as a dimer in high levels of secretions such as milk, tears, and saliva. What is the primary function of IgA in secretions?
To neutralize toxins and pathogens
What is the function of a memory T cell?
To provide an almost immediate response upon subsequent exposure to a specific pathogen
What are TLRs?
Toll-like receptors present on cells of innate immune system (macrophages and dendritic cells). Have ability to recognize PAMPS.
How are e β-defensins and cathelicidins produced in the epidermis of the skin?
Top panel: the epidermis has multiple layers of keratinocytes in different stages of differentiation arising from the basal layer of stem cells. Differentiated keratinocytes in the stratum spinosum produce β-defensins and cathelicidins, which are incorporated into secretory organelles called lamellar bodies (yellow) and secreted into the intercellular space to form a waterproof lipid layer (the stratum corneum) containing antimicrobial activity.
Within the nested events of the immune response, which of the following occurs when recruitment of effector cells fail to eliminate the pathogen?
Transport of antigens to lymphoid organs
Strep throat is commonly caused by group A Streptococcus bacteria. A common symptom of strep throat is the presence of swollen lymph nodes in the neck. This symptom usually peaks about 2-4 days after the onset of the infection, and is due to:
Trapping and activation of antigen-specific lymphocytes in the lymph nodes of the neck
Strep throat is commonly caused by group A Streptococcusbacteria. A common symptom of strep throat is the presence of swollen lymph nodes in the neck. This symptom usually peaks about 2-4 days after the onset of the infection, and is due to:
Trapping and activation of antigen-specific lymphocytes in the lymph nodes of the neck
Which type of T helper cell inhibits inflammation?
Treg
Which of the following description is correct about T regulatory cells (Treg cells)?
Treg cells express FoxP3 transcription factor
Which of the following description is NOT correct about T regulatory cells (Treg cells)?
Treg cells express both IL-2 and high affinity IL-2 receptor
A single molecule of IgM can activate the C1q component of the classical complement pathway (true or false)
True
After antigen binds to a B-cell antigen receptor, or B-cell receptor (BCR), the B-cell will proliferate and differentiate into plasma cells. These are the effector form of B lymphocytes, and they secrete antibodies that have the same antigen specificity as the plasma cell's B-cell receptor.
True
Antibody binding to a pathogen surface is greatly enhanced when both antigen-binding sites of the antibody are engaged at once, a feature known as bivalent binding. It is possible for antibodies to bind bivalently to a wide variety of components on many different pathogen surfaces due to the flexibility in the protein at the hinge region and at the V-C junction
True
Dendritic cells are tissue resident myeloid cells that are highly phagocytic, like macrophages. However, dendritic cells do not play a major role in large-scale pathogen destruction; instead, they are important in initiating adaptive immune responses of T cells
True
For cells of the innate immune system, each individual cell has multiple pattern recognition receptors, and can recognize many different pathogens. In contrast, cells of the adaptive immune system each express only a single antigen receptor, and have a single specificity for pathogen recognition.
True
For cells of the innate system, each individual cell has multiple pattern recognition receptors, and can recognize many different pathogens. In contrast, cells of the adaptive immune system each express only a single antigen receptor, and have a single specificity for pathogen recognition.
True
Innate lymphoid cells and NK cells are effector cells that respond rapidly after encountering a pathogen. Several different subsets of innate lymphoid cells exist, and each is specialized to respond to a category of pathogen (e.g., viruses, extracellular bacteria, helminthic parasites, etc.) Innate lymphoid cells reside primarily in tissues such as the lungs, the lining of the gastrointestinal tract, and the skin, because these sites represent the major routes of entry of pathogens into the body.
True
MBL has a function in the lectin pathway analagous to that of IgM in the classical pathway, and MASP-1 and MASP-2 are analogous to components in the C1 complex.
True
MHC class I molecules generally bind peptides that are 8-10 amino acids. Each allelic variant has preferences for the amino acid residues at key anchor positions, but will not bind every possible peptide containing the correct anchor residues
True
Many parasites produce a variety of soluble and membrane-associated proteins that can counteract complement activation and contribute to infection of the host by the microbe.
True
Most healthy epithelial surfaces are also associated with a large population of normally nonpathogenic bacteria, known as commensal bacteria or the microbiota.
True
Neutrophils regulate the production of active cathelicidins (a class of antimicrobial peptides) by segregating the inactive propeptide from the processing enzyme the cleaves and activates it in two different types of cytoplasmic granules. These two types of granules are induced to fuse with phagosomes after ingestion of microbes, bringing the processing enzyme and the propeptide together.
True
One factor that contributes to the enhanced secondary response to an antigen is the increased number of antigen-specific lymphocytes present after the primary response; these are known as memory cells.
True
Several pathogens produce proteins, either membrane-bound or secreted, that inactivate C3b that might be deposited on the pathogen surface. C3b is specifically targeted due to its central position in all three complement pathways
True
T cells expressing : TCRs are distinct from those expressing : TCRs in that they do not generally recognize host cell responses to infections or tissue damage; rather they recognize components of the pathogen directly.
True
T or F: All autoreactive CD4 T cells are not necessarily able to cause autoimmune diseases. Depending on the target tissue expressing the antigen recognized by the effector CD4 T cells, and the cytokines made by these effector T cells, autoimmune tissue damage may or may not occur.
True
T or F: Although most Fc receptors are expressed on cell surface, TRIM21 is an example of intracellular Fc receptor.
True
T or F: B-cell receptors and T-cell receptors share a mechanism for generating diversity, and also share structural homology in their V domains.
True
T or F: Cytotoxic T cells that lack expression of perforin aremore defective in killing target cells than those that lack granzymes.
True
T or F: Each family of NK cell receptors has members that promote NK cell activation, and members that send inhibitory signals when engaged. The difference between activating and inhibitory receptors lies in their association with accessory proteins that promote downstream signaling, or in their ability to recruit and activate inhibitory phosphatases, respectively.
True
T or F: In the majority of viral infections, CD8 T-cell activation requires CD4 T-cell help.
True
T or F: Intestinal epithelium and lamina propria contain a large number of effector T cells, plasma cells, and cytokine-secreting leukocytes even in the absence of infection; however, such an inflammatory state does not cause tissue damage because their effects are balanced by the presence of Treg cells and production of anti-inflammatory cytokines such as IL-10.
True
T or F: Like TCR signaling, B cell receptor (BCR) signaling is initiated by a Src-family kinase phosphorylating tyrosine resides in ITAM motifs of BCR signaling subunits.
True
T or F: Naïve CD8 T cell can be activated by dendritic cells that express high levels of co-stimulatory molecules. "Bystander" CD8 T cells can also be activated by IL-12 and IL-18 produced by activated dendritic cells. However, to generate optimal CD8 T cell memory, help from CD4 T cells is necessary.
True
T or F: Oral tolerance to food antigens and immune tolerance to gut microbiota share the property that foreign antigens encountered in the gastrointestinal (GI) tract—food and commensal microbes, respectively—do not elicit immune effector responses. Yet, these processes differ in that commensal microbes will still elicit protective adaptive immune responses if they cross the GI epithelium and enter the body.
True
T or F: The antibody protein has two functional domains, one for antigen binding and a second to confer specific effector functions. These two functional domains are encoded by the antibody light chain and antibody heavy chain polypeptides, respectively.
True
T or F: The immune response is a dynamic process that initiates with an antigen-independent response, which becomes more focused and powerful as it develops antigen specificity.
True
T or F: Unlike innate immune responses, adaptive immune responses are initiated in secondary lymphoid organs. However, the innate immune response to an infection in a tissue has a pivotal role in inducing T-cell responses in the nearest lymph node by activating tissue dendritic cells and inducing their migration to the lymph node.
True
T/F: All autoreactive CD4 T cells are not necessarily able to cause autoimmune diseases. Depending on the target tissue expressing the antigen recognized by the effector CD4 T cells, and the cytokines made by these effector T cells, autoimmune tissue damage may or may not occur.
True
T/F: Even when the donor HLA haplotype matches that of the recipient's, there will still be chronic rejection to the transplanted organ due to the presence of minor histocompatibility antigens.
True
T/F: Intestinal epithelium and lamina propria contain a large number of effector T cells, plasma cells, and cytokine-secreting leukocytes even in the absence of infection; however, such an inflammatory state does not cause tissue damage because their effects are balanced by the presence of Treg cells and production of anti-inflammatory cytokines such as IL-10.
True
T/F: Naive CD8 T cells can be activated by dendritic cells that express high levels of co-stimulatory molecules. "Bystander" CD8 T cells can also be activated by IL-22 and IL-28 produced by activated dendritic cells. However, to generate optimal CD8 T cell memory, help from CD4 T cells is necessary.
True
TH1, TH2, TH17, and T follicular helper (TFH) cells represent four different subsets of CD4 effector cells. Each of these subsets produces a distinct set of cytokines when stimulated, that in turn, act to mobilize distinct immune effector mechanisms. While TH1, TH2, and TH17 cells recruit and activate innate immune cells, TFH cells act to amplify the adaptive immune response.
True
The C3 convertase of the alternative complement pathway amplifies the overall magnitude of complement activation regardless of which of the three pathways initiated the complement activation initially
True
The C3 convertase of the alternative complement pathway can be formed using C3b created by any pathway, amplifying the overall magnitude of complement activation regardless of which of the three pathways initiated the complement activation initially. (true or false)
True
The NADPH oxidase reaction results in a transient increase in oxygen consumption by the cell, which is known as the respiratory burst.
True
The adaptive and innate immune responses use many of the same effector mechanisms to eliminate invading microorganisms.
True
The inflammatory response is characterized by four classic symptoms: heat, redness, pain, and swelling. In some instances, this response can be triggered by a stimuli that are non-infectious such as asbestos, a process known as 'sterile inflammation.' When exposure to the stimulating trigger is persistent, a state of chronic inflammation can result. This process is likely to be detrimental to the health of the host.
True
The spleen is a secondary lymphoid organ that performs several functions. In addition to its role as a site for initiating adaptive immune responses, the spleen is important in removing dead or damaged red blood cells from the circulation. Its immune function is important because blood-borne pathogens will not be transported to draining lymph nodes via the lymph fluid.
True
True or False: Each family of NK cell receptors has members that promote NK cell activation, and members that send inhibitory signals when engaged. The difference between activating and inhibitory receptor lies in their association with accessory proteins that promote downstream signaling, or in their ability to recruit and activate inhibitory phosphatases, respectively.
True
True or False: Each family of NK cell receptors has members that promote NK cell activation, and members that send inhibitory signals when engaged. The difference between activating and inhibitory receptors lies in their association with accessory proteins that promote downstream signaling, or in their ability to recruit and activate inhibitory phosphatases, respectively.
True
True/False: Antibody binding to a pathogen surface is greatly enhanced when both antigen-binding sites of the antibody are engaged at once, a feature known as bivalent binding. It is possible for antibodies to bind bivalently to a wide variety of components on many different pathogen surfaces due to the flexibility in the protein at the hinge region and at the V-C junction.
True
True/False: Dendritic cells are tissue resident myeloid cells that are highly phagocytic, like macrophages. However, dendritic cells do not play a major role in large-scale pathogen destruction; instead, they are important in initiating adaptive immune responses of T cells.
True
True/False: Each family of NK cell receptors has members that promote NK cell activation, and members that send inhibitory signals when engaged. The difference between activating and inhibitory receptors lies in their association with accessory proteins that promote downstream signaling, or in their ability to recruit and activate inhibitory phosphatases, respectively.
True
True/False: For cells of the innate immune system, each individual cell has multiple pattern recognition receptors, and can recognize many different pathogens. In contrast, cells of the adaptive immune system each express only a single antigen receptor, and have a single specificity for pathogen recognition.
True
True/False: MHC class I molecules generally bind peptides that are 8-10 amino acids. Each allelic variant has preferences for the amino acid residues at key anchor positions, but will not bind every possible peptide containing the correct anchor residues.
True
True/False: Neutrophils regulate the production of active cathelicidins (a class of antimicrobial peptides) by segregating the inactive propeptide from the processing 4 enzyme that cleaves and activates it in two different types of cytoplasmic granules. These two types of granules are induced to fuse with phagosomes after ingestion of microbes, bringing the processing enzyme and the propeptide together.
True
True/False: One factor that contributes to the enhanced secondary response to an antigen is the increased number of antigen-specific lymphocytes present after the primary response; these are known as memory cells.
True
True/False: Several pathogens produce proteins, either membrane-bound or secreted, that inactivate C3b that might be deposited on the pathogen surface. C3b is specifically targeted due to its central position in all three complement pathways.
True
True/False: T cells expressing : TCRs are distinct from those expressing : TCRs in that they do not generally recognize host cell responses to infections or tissue damage; rather they recognize components of the pathogen directly.
True
True/False: TH1, TH2, TH17, and T follicular helper (TFH) cells represent four different subsets of CD4 effector cells. Each of these subsets produces a distinct set of cytokines when stimulated, that in turn, act to mobilize distinct immune effector mechanisms. While TH1, TH2, and TH17 cells recruit and activate innate immune cells, TFH cells act to amplify the adaptive immune response.
True
True/False: The C3 convertase of the alternative complement pathway amplifies the overall magnitude of complement activation regardless of which of the three pathways initiated the complement activation initially.
True
True/False: The MHC locus encodes a large number of genes spanning over four million bp of DNA. These include many genes involved in antigen processing and presentation, as well as receptors recognized by non-conventional T cells and natural killer (NK) cells. In addition, the MHC locus encodes genes with no function in immunity at all.
True
True/False: The extravasation of neutrophils into tissues at sites of infection or inflammation requires changes to both the endothelium and to the neutrophil that are induced by chemokines and cytokines produced in the infected tissue.
True
True/False: The genes encoding MHC proteins are closely linked with genes encoding proteins involved in antigen processing and presentation. This genetic linkage facilitates the coordinate regulation of these genes by interferons.
True
True/False: The inflammatory response is characterized by four classic symptoms: heat, redness, pain, and swelling. In some instances, this response can be triggered by stimuli that are non-infectious such as asbestos, a process known as 'sterile inflammation.' When exposure to the stimulating trigger is persistent, a state of chronic inflammation can result. This process is likely to be detrimental to the health of the host.
True
True/False: The spleen is a secondary lymphoid organ that performs several functions. In addition to its role as a site for initiating adaptive immune responses, the spleen is important in removing dead or damaged red blood cells from the circulation. Its immune function is important because blood-borne pathogens will not be transported to draining lymph nodes via the lymph fluid.
True
True/False: When a B cell differentiates into a plasma cell, it goes from expressing membrane-bound IgM to making mostly the secreted form of IgM. A deletion of the first polyadenylation site in the μ heavy chain gene would prevent activated B cells from making the secreted form of IgM.
True
True/False: When first discovered, investigators found it surprising that some single- gene defects causing immunodeficiency syndromes were associated with hypersensitivities to ionizing radiation, thereby leading to increased rates of cancer. The genes accounting for this dual impairment encode ubiquitously expressed DNA repair proteins.
True
Type 1 interferons activate natural killer cells that selectively kill virus infected cells.
True
The C3 convertase of the alternative complement pathway amplifies the overall magnitude of complement activation regardless of which of the three pathways initiated the complement activation initially.
True The C3 convertase of the alternative pathway contains C3b, allowing it to generate more of itself and amplify the overall level of C3b formed. Since C3b is a common intermediate for all three pathways of complement activation, once the initial C3b is generated by any of the pathways, the recruitment of factor B, and cleavage by factor D can proceed. By this mechanism, the initial C3b generated forms an amplification loop leading to more C3b, regardless of how the initial C3b was made.
Several pathogens produce proteins, either membrane-bound or secreted, that inactivate C3b that might be deposited on the pathogen surface. C3b is specifically targeted due to its central position in all three complement pathways.
True. All three pathways of complement activation converge on the assembly of a C3 convertase that produces C3b bound to the pathogen surface. Therefore, pathogens that can inactivate bound C3b can interfere with complement activation that might be initiated by any of the three pathways. This makes C3b an ideal target for an immune evasions strategy.
True/False: The extravasation of neutrophils into tissues at sites of infection or inflammation requires changes to both the endothelium and to the neutrophil that are induced by chemokines and cytokines produced in the infected tissue.
True. Both the endothelium and the neutrophils respond to cytokines and chemokines made in the tissue in response to infection. For the endothelium, the changes include vascular dilation and up-regulation of P-selectin, E-selectin, and ICAM molecules. For the neutrophil, the chemokines bound to proteoglycans on the surface of the endothelial cells induce a conformational change in the integrins on the surface of the neutrophil, converting them into high affinity binding partners for the ICAMs on the activated endothelium.
True/False: Dendritic cells are tissue resident myeloid cells that are highly phagocytic, like macrophages. However, dendritic cells do not play a major role in large-scale pathogen destruction; instead, they are important in initiating adaptive immune responses of T cells.
True. Dendritic cells are considered to be the bridge between innate and adaptive immunity. They are tissue resident cells that rapidly respond to infections, due to their expression of many PRRs. However, unlike macrophages and neutrophils, the latter of which are recruited to infected tissues, dendritic cells do not function in large-scale pathogen destruction. Instead, they phagocytose pathogens and degrade them to generate peptides for presentation and activation of T cells.
True/False: Each family of NK cell receptors has members that promote NK cell activation, and members that send inhibitory signals when engaged. The difference between activating and inhibitory receptors lies in their association with accessory proteins that promote downstream signaling, or in their ability to recruit and activate inhibitory phosphatases, respectively.
True. KIRs and KLRs are two different families of NK cell receptors. Each has members that send activating signals to the NK cell and members that send inhibitory signals. The activating receptors associate with a signaling adapter protein, called DAP12, that contains amino acid sequence motifs known as ITAMs. When phosphorylated, ITAM sequences recruit tyrosine kinases to promote NK cell activation. In contrast, inhibitory receptors generally have longer cytoplasmic tails than the activating receptors. Rather than associating with an adapter protein such as DAP12, these receptors have amino acid motifs known as ITIMs in their cytoplasmic tails. ITIM motifs recruit inhibitory phosphatases when the receptor is stimulated, and therefore, down-regulate signaling in the NK cell.
True/False: The inflammatory response is characterized by four classic symptoms: heat, redness, pain, and swelling. In some instances, this response can be triggered by stimuli that are non-infectious such as asbestos, a process known as 'sterile inflammation.' When exposure to the stimulating trigger is persistent, a state of chronic inflammation can result. This process is likely to be detrimental to the health of the host.
True. The inflammatory response is effective at promoting immunity and eradicating infections, but at the same time causes damage to the host. The influx of fluid and cells into tissues can cause damage, and the production of antimicrobial compounds, such as toxic oxygen and nitrogen species, also causes collateral damage. Inflammatory responses also induce tissue repair, a process that when chronic can also lead to tissue damage.
True/False: Neutrophils regulate the production of active cathelicidins (a class of antimicrobial peptides) by segregating the inactive propeptide from the processing enzyme that cleaves and activates it in two different types of cytoplasmic granules. These two types of granules are induced to fuse with phagosomes after ingestion of microbes, bringing the processing enzyme and the propeptide together.
True. All antimicrobial peptides, including cathelicidins, are produced as inactive propeptides. The active forms of the peptides are generated following proteolytic cleavage of the propeptides. Neutrophils constitutively produce cathelicidins, which are synthesized as inactive propeptides. The inactive cathelicidin propeptides are stored in secondary granules, whereas the cleavage enzyme, neutrophil elastase, is stored in primary granules. These two types of granules are induced to fuse with phagocytic vesicles, called phagosomes, after the neutrophil has engulfed a pathogen. This fusion brings the cleavage enzyme together with the cathelicidin propeptide, leading to cathelicidin activation.
True/False: Several pathogens produce proteins, either membrane-bound or secreted, that inactivate C3b that might be deposited on the pathogen surface. C3b is specifically targeted due to its central position in all three complement pathways.
True. All three pathways of complement activation converge on the assembly of a C3 convertase that produces C3b bound to the pathogen surface. Therefore, pathogens that can inactivate bound C3b can interfere with complement activation that might be initiated by any of the three pathways. This makes C3b an ideal target for an immune evasions strategy.
1.19 True/False: For cells of the innate immune system, each individual cell has multiple pattern recognition receptors, and can recognize many different pathogens. In contrast, cells of the adaptive immune system each express only a single antigen receptor, and have a single specificity for pathogen recognition.
True. Cells of the innate immune system generally express multiple pattern recognition receptors. Each of these receptors recognizes a conserved feature of a class of pathogens. Therefore, a single innate immune cell can respond to a multitude of different pathogens. In contrast, the antigen receptor on B and T lymphocytes is clonally distributed; each single cell expresses only one version of this receptor, and has a single binding specificity.
True/False: For cells of the innate immune system, each individual cell has multiple pattern recognition receptors, and can recognize many different pathogens. In contrast, cells of the adaptive immune system each express only a single antigen receptor, and have a single specificity for pathogen recognition.
True. Cells of the innate immune system generally express multiple pattern recognition receptors. Each of these receptors recognizes a conserved feature of a class of pathogens. Therefore, a single innate immune cell can respond to a multitude of different pathogens. In contrast, the antigen receptor on B and T lymphocytes is clonally distributed; each single cell expresses only one version of this receptor, and has a single binding specificity.
True/False: Innate lymphoid cells and NK cells are effector cells that respond rapidly after encountering a pathogen. Several different subsets of innate lymphoid cells exist, and each is specialized to respond to a category of pathogen (e.g., viruses, extracellular bacteria, helminthic parasites, etc). Innate lymphoid cells reside primarily in tissues such as the lungs, the lining of the gastrointestinal tract, and the skin, because these sites represent the major routes of entry of pathogens into the body
True. Innate lymphoid cells are tissue-resident cells found primarily in the lung epithelium, the skin, and the intestinal epithelium. Since most pathogens enter the body through one of these sites, it is important to post innate immune cells in these locations where they will readily encounter a pathogen that has breached one of the body's barriers
1.12 True/False: Innate lymphoid cells and NK cells are effector cells that respond rapidly after encountering a pathogen. Several different subsets of innate lymphoid cells exist, and each is specialized to respond to a category of pathogen (e.g., viruses, extracellular bacteria, helminthic parasites, etc). Innate lymphoid cells reside primarily in tissues such as the lungs, the lining of the gastrointestinal tract, and the skin, because these sites represent the major routes of entry of pathogens into the body.
True. Innate lymphoid cells are tissue-resident cells found primarily in the lung epithelium, the skin, and the intestinal epithelium. Since most pathogens enter the body through one of these sites, it is important to post innate immune cells in these locations where they will readily encounter a pathogen that has breached one of the body's barriers.
1.7 True/False: In the absence of an infection, most granulocytes (neutrophils, eosinophils, basophils) are found circulating in the blood, whereas other subsets of myeloid cells reside in tissues.
True. Mast cells and macrophages are both cells of the myeloid lineage. These are tissue-resident cells that are poised to respond rapidly if an infectious microbe enters their tissue of residence.
True/False: In the absence of an infection, most granulocytes (neutrophils, eosinophils, basophils) are found circulating in the blood, whereas other subsets of myeloid cells reside in tissues.
True. Mast cells and macrophages are both cells of the myeloid lineage. These are tissue-resident cells that are poised to respond rapidly if an infectious microbe enters their tissue of residence.
1.36 True/False: TH1, TH2, TH17, and T follicular helper (TFH) cells represent four different subsets of CD4 effector cells. Each of these subsets produces a distinct set of cytokines when stimulated, that in turn, act to mobilize distinct immune effector mechanisms. While TH1, TH2, and TH17 cells recruit and activate innate immune cells, TFH cells act to amplify the adaptive immune response.
True. Most CD4 effector cells produce cytokines that act on innate immune cells, For instance, TH1 cells activate macrophages, TH2 cells recruit and activate mast cells, basophils, and eosinophils, and TH17 cells recruit neutrophils. Unlike these subsets, TFH cells function to promote B cell activation and antibody responses, and thus help amplify the adaptive immune response.
True/False: TH1, TH2, TH17, and T follicular helper (TFH) cells represent four different subsets of CD4 effector cells. Each of these subsets produces a distinct set of cytokines when stimulated, that in turn, act to mobilize distinct immune effector mechanisms. While TH1, TH2, and TH17 cells recruit and activate innate immune cells, TFH cells act to amplify the adaptive immune response.
True. Most CD4 effector cells produce cytokines that act on innate immune cells, For instance, TH1 cells activate macrophages, TH2 cells recruit and activate mast cells, basophils, and eosinophils, and TH17 cells recruit neutrophils. Unlike these subsets, TFH cells function to promote B cell activation and antibody responses, and thus help amplify the adaptive immune response.
1.29 True/False: One factor that contributes to the enhanced secondary response to an antigen is the increased number of antigen-specific lymphocytes present after the primary response; these are known as memory cells.
True. Several factors contribute to the enhanced secondary response to an antigen. One of these is the clonal expansion of antigen-specific lymphocytes that occurs during the primary response. While many of these cells die after the antigen is cleared, a subset of them remain as long-lived memory cells.
True/False: One factor that contributes to the enhanced secondary response to an antigen is the increased number of antigen-specific lymphocytes present after the primary response; these are known as memory cells.
True. Several factors contribute to the enhanced secondary response to an antigen. One of these is the clonal expansion of antigen-specific lymphocytes that occurs during the primary response. While many of these cells die after the antigen is cleared, a subset of them remain as long-lived memory cells.
True/False: The C3 convertase of the alternative complement pathway amplifies the overall magnitude of complement activation regardless of which of the three pathways initiated the complement activation initially.
True. The C3 convertase of the alternative pathway contains C3b, allowing it to generate more of itself and amplify the overall level of C3b formed. Since C3b is a common intermediate for all three pathways of complement activation, once the initial C3b is generated by any of the pathways, the recruitment of factor B, and cleavage by factor D can proceed. By this mechanism, the initial C3b generated forms an amplification loop leading to more C3b, regardless of how the initial C3b was made
True/False: The spleen is a secondary lymphoid organ that performs several functions. In addition to its role as a site for initiating adaptive immune responses, the spleen is important in removing dead or damaged red blood cells from the circulation. Its immune function is important because blood-borne pathogens will not be transported to draining lymph nodes via the lymph fluid.
True. The spleen is important for trapping blood-borne pathogens so they can be taken up and degraded by dendritic cells for presentation to T lymphocytes to initiate adaptive immune responses.
PD-1 is a negative co-stimulatory signal expressed by tumor cells. What advantage would the expression of PD-1 have in a tumor cell avoiding the immune response?
Tumor cells can avoid being killed by activated TC cells.
Although homozygous deficiencies in complement regulatory proteins cause serious diseases, more subtle alterations in the balance of complement activation versus inhibition have been found to contribute to disease susceptibility. Describe the genetic evidence linking subtle alterations in complement regulatory proteins to disease susceptibility.
Two genetic alterations in complement regulatory proteins are linked to disease susceptibility. People heterozygous for mutations in one of many complement regulatory proteins are one example, like MCP and Factor I or H. They're predisposed to hemolytic disease with damage to platelets/RBCs and kidney inflammation. Also, people with certain single-nucleotide polymorphisms in the factor H gene are predisposed to macular degeneration, an age-related disease that causes blindness. Polymorphisms in other complement genes also contribute to susceptibility of age-related macular degeneration.
he basic immunoglobulin (Ig) unit is composed of
Two identical heavy chains and two identical light chains
Although the complement cascade can be initiated by antibodies bound to the surface of a pathogen, complement activation is generally considered to be an innate immune response. This is because:
Two of the three pathways for complement activation are initiated by constitutively produced recognition molecules that directly interact with microbial surfaces. There are three pathways for initiating complement activation. One of them, known as the classical pathway, occurs when the pathogen has antibodies bound to its surface, leading to recruitment of C1q. The other two pathways, the lectin pathway and the alternative pathway, are initiated by mechanisms that do not require antibodies directed against the pathogen surface. These latter two pathways are dependent on constitutively produced, and therefore 'innate' recognition molecules that directly bind to pathogen surfaces, initiating complement activation.
Although the complement cascade can be initiated by antibodies bound to the surface of a pathogen, complement activation is generally considered to be an innate immune response. This is because:
Two of the three pathways for complement activation are initiated by constitutively produced recognition molecules that directly interact with microbial surfaces.
Although homozygous deficiencies in complement regulatory proteins cause serious diseases, more subtle alterations in the balance of complement activation versus inhibition have been found to contribute to disease susceptibility. Describe the genetic evidence linking subtle alterations in complement regulatory proteins to disease susceptibility.
Two types of genetic alterations in complement regulatory proteins have been linked to disease susceptibility. First, individuals heterozygous for mutations in one of several complement regulatory proteins (MCP, factor I, factor H). These individuals are predisposed to develop a hemolytic disease that leads to damage to platelets and red blood cells, and to kidney inflammation. Second, individuals with particular single- nucleotide polymorphisms in the gene for factor H are predisposed to macular degeneration, an age-related disease that causes blindness. Furthermore, polymorphisms in other complement genes have been found to contribute to the susceptibility to age-related macular degeneration.
Although homozygous deficiencies in complement regulatory proteins cause serious diseases, more subtle alterations in the balance of complement activation versus inhibition have been found to contribute to disease susceptibility. Describe the genetic evidence linking subtle alterations in complement regulatory proteins to disease susceptibility.
Two types of genetic alterations in complement regulatory proteins have been linked to disease susceptibility. First, individuals heterozygous for mutations in one of several complement regulatory proteins (MCP, factor I, factor H). These individuals are predisposed to develop a hemolytic disease that leads to damage to platelets and red blood cells, and to kidney inflammation. Second, individuals with particular single-nucleotide polymorphisms in the gene for factor H are predisposed to macular degeneration, an age-related disease that causes blindness. Furthermore, polymorphisms in other complement genes have been found to contribute to the susceptibility to age-related macular degeneration.
Expression of a CD8 α:α homodimer is characteristic of:
Type b intraepithelial lymphocytes (IELs)
Multiple pathways for regulating complement activation limit the potential damage caused by complement deposition on host cells or caused by the spontaneous activation of complement proteins in the plasma. Genetic deficiencies in these mechanisms often lead to chronic inflammatory diseases, but in some cases can paradoxically lead to increased susceptibility to bacterial infections. This latter outcome may occur because:
Uncontrolled complement activation leads to the depletion of serum complement proteins. Individuals with a genetic defect in factor I are subject to recurrent infections with pyogenic (pus-forming) extracellular bacterial infections. This occurs because, in the absence of factor I, uncontrolled complement activation ends up depleting the complement proteins from the plasma. This leads to impaired complement activation on these bacteria, and therefore, to diminished clearance of these infections.
Hepatitis C is a virus that infects hepatocytes, which are non-immune cells of the liver. Currently, patients with chronic Hepatitis C infections are treated with repeated administration of type I interferon, predominantly interferon . One aspect of this treatment that might aid the patient's immune system in clearing this virus infection is:
Up-regulation of MHC class I expression levels on hepatocytes
Hepatitis C is a virus that infects hepatocytes, which are non-immune cells of the liver. Currently, patients with chronic Hepatitis C infections are treated with repeated administration of type I interferon, predominantly interferon . One aspect of this treatment that might aid the patient's immune system in clearing this virus infection is: (Hint: HCV replicates in the cytosol of hepatocytes)
Upregulation of MHC class I expression levels on hepatocytes
Hepatitis C is a virus that infects hepatocytes, which are non-immune cells of the liver. Currently, patients with chronic Hepatitis C infections are treated with repeated administration of type I interferon, predominantly interferon alpha. One aspect of this treatment that might aid the patient's immune system in clearing this virus infection is:(Hint: HCV replicates in the cytosol of hepatocytes)
Upregulation of MHC class I expression levels on hepatocytes
Match the T cell integrin proteins to their binding partners on endothelial cells: VLA-4
VCAM-1
Which of the following is NOT a feature of germinal center B-cells?
VDJ recombination
Which of the following domains corresponds to the antigen binding site of immunoglobulins?
VH:VL
Which of the following domains corresponds to the antigen binding site of immunoglobulins?
V_H : V_L
Individuals or mice with defects in the biochemical pathways needed for loading peptides onto MHC molecules show greatly increased susceptibility to virus infections. Experiments examining the MHC molecules present on the surface of host cells in these individuals would show:
Very low levels of total MHC proteins expressed on the cell surface.
Individuals with defects in the biochemical pathways needed for loading peptides onto MHC molecules show greatly increased susceptibility to virus infections. Experiments examining the MHC molecules present on the surface of host cells in these individuals would show:
Very low levels of total MHC proteins expressed on the cell surface.
Antibodies, complement proteins, and phagocytic cells provide effective protection against all of the following types of infections, except:
Virus-Infected Cells
In a recent experiment, NK cells were collected from an MCMV infected mouse, 50 days after infection, and placed into a healthy mouse. Upon exposure to the MCMV virus, the healthy mouse quickly mounted an immune response. How could these results BEST be interpreted?
What is measured by the cell-mediated lympholysis (CML) assay?
The germinal center is a region within the secondary B cell follicle where sustained B cell proliferation and differentiation take place. The processes of B cell proliferation and differentiation, including affinity maturation and class switching, require periodic interactions of the germinal center B cells with CD4 TFH cells. These periodic interactions between the B cells and TFH cells can occur:
When B cells cycle between the dark zone and the light zone of the germinal center
what happens when COMMENSAL MICROORGANISMS are killed by antibiotics treatments?
When commensal microorganisms are killed by antibiotic treatment, pathogens frequently replace them and cause disease
Recent studies using mouse models of pulmonary inflammation (a model for human asthma) have found that mice deficient in the C3a receptor have greatly reduced disease symptoms when challenged with inhaled preparations containing extracts of the fungal pathogen Aspergillus fumigatus. Specifically, the C3a receptor- deficient mice showed reduced influx of granulocytes and lymphocytes into the lung and reduced fluid in the lung after challenge. What is the explanation for these findings?
When complement is activated in the lung in response to the inhaled preparations of the fungus, the C3 convertase generates C3a. C3a induces a local inflammatory response in the lung, by acting on the vascular endothelial cells. This response includes increased vascular permeability, leading to an increase of fluid in the lung, and also acts to up- regulate adhesion molecules on the local vascular endothelium. As a result, there is increased recruitment of granulocytes, monocytes, and lymphocytes into the lung.
Recent studies using mouse models of pulmonary inflammation (a model for human asthma) have found that mice deficient in the C3a receptor have greatly reduced disease symptoms when challenged with inhaled preparations containing extracts of the fungal pathogen Aspergillus fumigatus. Specifically, the C3a receptor-deficient mice showed reduced influx of granulocytes and lymphocytes into the lung and reduced fluid in the lung after challenge. What is the explanation for these findings?
When complement is activated in the lung in response to the inhaled preparations of the fungus, the C3 convertase generates C3a. C3a induces a local inflammatory response in the lung, by acting on the vascular endothelial cells. This response includes increased vascular permeability, leading to an increase of fluid in the lung, and also acts to up-regulate adhesion molecules on the local vascular endothelium. As a result, there is increased recruitment of granulocytes, monocytes, and lymphocytes into the lung.
A common characteristic of a site of infection, such as a pimple on the skin, is pus. What is responsible for the white color of pus?
White blood cells, primarily neutrophils. Pus is an inflammatory response to a bacterial infection of the skin. The inflammatory response recruits neutrophils from the blood into the site of infection, along with some monocytes.
1.11 Short answer: A common characteristic of a site of infection, such as a pimple on the skin, is pus. What is responsible for the white color of pus?
White blood cells, primarily neutrophils. Pus is an inflammatory response to a bacterial infection of the skin. The inflammatory response recruits neutrophils from the blood into the site of infection, along with some monocytes.
A common characteristic of a site of infection, such as a pimple on the skin, is pus. What is responsible for the white color of pus?
White blood cells, primarily neutrophils. Pus is an inflammatory response to a bacterial infection of the skin. The inflammatory response recruits neutrophils from the blood into the site of infection, along with some monocytes.
D
[11]. Which of the following accounts for the transition from membrane-bound IgM to secreted IgM upon activation of a B cell? a. Affinity maturation b. Class switch recombination c. Additional modification of nuclear DNA via RAG-1/2 d. Alternative splicing of pre-mRNA e. None of the above
C
[13]. Even when the complement cascade fails to proceed beyond generating the C3 convertase, complement activation is effective at inducing pathogen uptake and destruction. This process of immune protection is mediated by: a. Activation of complement inhibitory receptors on phagocytes that promote pathogen uptake. b. Activation of soluble proteases in the serum that disrupt pathogen membranes. c. Engagement of complement receptors on phagocytes by C3b and its cleavage products which promotes phagocytosis. d. Engagement of complement receptors on T cells that promotes antibody production. e. Stimulation of antimicrobial peptide secretion by phagocytes.
E
[14]. Given the enormous heterogeneity of antigen receptors expressed on the populations of naïve B and T lymphocytes, the adaptive immune response relies on a process whereby the rare lymphocyte that binds to the antigen is first induced to proliferate, before it can perform its effector function. For B cells, there is a clever mechanism that ensures that the specificity of the antibody secreted by the plasma cell will recognize the same pathogen that initially stimulated the B cell antigen receptor and induced B cell proliferation. This mechanism is: a. The naïve B cell expresses an array of different B cell antigen receptors and randomly chooses which specificity of antibody to secrete as a plasma cell. b. The naïve B cell expresses a single specificity of B cell antigen receptor and then up-regulates the expression of this receptor so it can bind tightly to the pathogen. c. The plasma cell proliferates after it has finished secreting antibody to generate more plasma cells with specificity for the pathogen. d. The plasma cell traps secreted antibody molecules in its extracellular matrix and uses these antibodies to bind to the pathogen. e. The naïve B cell expresses a membrane-bound form of the antibody as a receptor and secretes that same antibody when it differentiates into a plasma cell.
C
[15]. The positions within the MHC protein where most of the allelic sequence variation occurs are not randomly distributed, but are concentrated in certain regions of the MHC protein. This indicates: a. That MHC allelic polymorphism has been driven by selection for diversity in the β2-microglobulin. b. That MHC genes are more susceptible to bind self peptides than foreign peptide. c. That MHC allelic polymorphism has been driven by selection for diversity in peptide binding specificity. d. That MHC genes are more susceptible to bind foreign peptides than self peptide. e. That MHC polymorphism has evolved to prevent pathogens that infect non-human primates from infecting humans.
A
[16]. Stimulation by viruses of the nucleic acid-sensing TLRs that reside in endosomal membranes induces the production of a different cytokine response than is produced by stimulation of the plasma membrane TLRs. The cytokine response following stimulation of nucleic acid-sensing TLRs is characterized by the production of: a. Type I interferon b. TNF-, which induces increased vascular permeability c. Antimicrobial peptides by macrophages d. Chemokines that recruit neutrophils e. The inflammatory complement fragments, C3a and C5a
C
[17]. The antibody surface involved in antigen binding varies depending on the size and nature of the antigen. This surface can be concave or flat, and sometimes, can have extended protrusions. This is accomplished by: a. Flexibility in the hinge regions of the antibody allowing rotation of the antigen-binding sites. b. Some antibodies using V region framework sequences instead of the CDRs to bind antigen. c. The ability of different CDR sequences to form many structurally distinct shapes and surfaces. d. The ability of the same heavy chain to pair with different light chains. e. The differential usage of κ versus λ light chains, as κ chains form concave binding sites whereas λ chains make flatter surfaces.
C
[18]. NK cells express receptors from several families, each of which has multiple members. Some of these receptors are activating and others are inhibitory, and NK cell activation is dependent on the balance of signaling overall. The NK cells found in an individual: a. Always express a majority of activating versus inhibitory receptors. b. Are more potent effectors of cytotoxicity than of cytokine production. c. Each express only a subset of all possible NK receptors. d. Are not considered members of the innate lymphoid cell lineage. e. Undergo massive proliferation in response to infection, similar to T lymphocytes.
E
[19]. Many different viruses encode proteins that function to down-regulate MHC class I expression on host cells following infection with the virus. This immune evasion mechanism allows the virus to hide from CD8 T lymphocytes that normally detect virus-infected cells by using their T cell antigen receptor to recognize viral peptides bound to MHC class I proteins on the surface of the infected cell. To counteract this immune evasion strategy, NK cells have: a. Activating receptors that recognize MHC class I proteins b. A mechanism to secrete antiviral peptides c. Inhibitory receptors that recognize viral capsid proteins d. Activating receptors that recognize viral capsid proteins e. Inhibitory receptors that recognize MHC class I proteins
D
[1]. How many complementarity-determining regions contribute to the antigen/MHC-binding site in an intact T-cell receptor? a. 2 b. 3 c. 4 d. 6 e. 12
C
[2]. Which of the following classes of cell surface receptors are directly encoded in the germline? a. TCR b. BCR c. PRR d. Antibodies e. All of the above
C
[3]. The "MHC _____" refers to the complete set of HLA alleles that a person possesses on a particular chromosome 6. a. isoform b. isotype c. haplotype d. allotype e. oligomorph
A
[4]. When macrophages in a tissue encounter bacteria, they release cytokines that induce an inflammatory response. These cytokines act on other immune cells, to recruit them to the site of infection and to enhance their activities. In addition, these cytokines act on the endothelial cells of the blood vessel wall to: a. Increase their permeability, allowing fluid and proteins to leak into the tissue b. Solidify the tight junctions to prevent the bacteria from entering the blood c. Proliferate, allowing the blood vessel to enlarge d. Up-regulate microbicidal mechanisms, so they can kill bacteria e. Secrete anti-microbial peptides
D
[6]. An infant with recurrent bacterial and fungal infections is suspected to have an immunodeficiency disease. Within two days after exposure to a pathogen, the organisms have proliferated to dangerous levels requiring immediate systemic antibiotic treatment. It is unlikely that this infant has a defect in B or T lymphocyte responses to the infection because: a. Bacteria and fungi do not require B cell or T cell responses for their clearance. b. Bacteria and fungi are not efficiently transported to draining lymph nodes to initiate adaptive immune responses. c. Systemic infections of bacteria and fungi are usually cleared by the spleen. d. The defective immune response occurs too rapidly following infection to be due to a defect in B or T lymphocytes responses. e. Adaptive immune responses require dendritic cells to take up and degrade pathogens.
acute phase proteins
[t] is a group of proteins rapidly produced by the liver during infection; includes C-reactive protein and mannose binding lectin for examples.
Which of the following is the best example of self-MHC restriction of T cells
a T cell clone only recognizes foreign peptides when presented by self MHC
Which of the following is the BEST example of herd immunity
a child infected with measles travels from Germany to the United States. Several babies contract the disease, but the outbreak is largely contained due to vaccinations
The TCR for an antigen is
a heterodimer
1.44 Synthesis question: One major difference between the innate and adaptive immune responses is in the mechanism by which pathogens are recognized. Innate immune cells use pattern recognition receptors (PRRs) to recognize conserved determinants shared by all the members of a category of pathogens, whereas adaptive immune cells (B and T lymphocytes) have highly specific antigen receptors. a) Which of the patterns of receptor expression in Figure Q1.44 represent innate immune cells? b) Which of the patterns of receptor expression represent B and T lymphocytes? c) Following an infection, how does the population of innate cells change? Starting with the cartoon representing your answer to part (a), draw the population present at one week post-infection. d) Following infection, how does the population of B and T lymphocytes change? Starting with the cartoon representing your answer to part (b), draw the population present at one week post-infection. PICTURE ON LAPTOP
a) A. Innate immune cells express multiple different receptors for recognizing PAMPs; however, all cells of the same innate subset express the same receptors. b) C. B and T lymphocytes each express only a single specificity of antigen receptor; however, each B or T cell expresses a different receptor from the other cells of the same subset. c) The population of innate cells is largely unchanged before and after infection. d) The rare B or T lymphocyte with an antigen receptor specific for the pathogen undergoes clonal expansion. This population is therefore much more abundant after infection than before. All other lymphocytes remain unchanged.
In vertebrates, complement activation generally involves a pathogen recognition step followed by a proteolytic cascade that produces the effector proteins that function in opsonization, membrane attack, and inflammation. a) Which of these is likely to be the most evolutionarily primitive aspect of the complement system? b) Which pathway of complement initiation is likely to be the one that most recently evolved?
a) The most primitive form is one that resembles our alternative complement pathway, with ancestral homologs of C3 and factor B that make a C3 convertase. This provides a mechanism for opsonizing bacteria and increasing their uptake by phagocytosis. These ancestral homologs have been found in echinoderms, and may have existed in more primitive organisms like corals and sea anemones. b) The latest evolutionary development is the classical pathway. It makes use of antibody binding to initiate complement activation. The adaptive immune system is only found in vertebrates.
In vertebrates, complement activation generally involves a pathogen recognition step followed by a proteolytic cascade that produces the effector proteins that function in opsonization, membrane attack, and inflammation. a) Which of these is likely to be the most evolutionarily primitive aspect of the complement system? b) Which pathway of complement initiation is likely to be the one that most recently evolved?
a) The most primitive form of a complement system is one that resembles our alternative complement pathway, with ancestral homologs of C3 and factor B that make a C3 convertase. This provides a mechanism for opsonizing infecting bacteria and increasing their phagocytosis by phagocytic cells. These ancestral homologs of C3 and factor B have been found in echinoderms, and may even have existed in even more primitive organisms such as corals and sea anemones. b) The latest evolutionary development in the complement system is the classical pathway, which makes use of antibody binding to initiate complement activation. The adaptive immune system, including the production of antibodies, is only found in vertebrates.
BCR signaling on B cells is initiated by antigen binding, leading to mTOR activation. This occurs, for instance, when the antigen is a live microbe that binds to the BCR on the B cells. Which one of the forms of antigen shown below the graph would correctly account for the data shown in Figure Q7.40.
a. (one with yellow antibody and microbe attachments)
TdT
a. Non-template addition of N-nucleotides
Pathogen killing during phagocytic process can occur via the contribution of a number of cellular processes. These include which of the following
activation of enzymes in the phagolysosome, ROS generation, granule fusion with phagolysoome, and RNS generation
The goal of _________ is to remove the insult that elicited a response whereas the goal of __________ is to adapt to the presence of an insult that cannot be eliminated.
acute inflammation; chronic inflammation
A(n) ____ is a molecule that is used by immune cells for: communication. Interleukin chemoattractant chemokine cytokine all of the above
all of the above
involves protease activity
all three pathways
uses the membrane attack complex
all three pathways
Recombination of Ig segments serves to __________________ (SELECT ALL THAT APPLY)
allow assembly of a complete BCR coding sequence promote BCR diversification
Which of the following accounts for the transition from membrane-bound IgM to secreted IgM upon activation of a B cell?
alternate splicing of pre-mRNA
active in C2 deficient mice
alternative pathway
uses factor B
alternative pathway
Three pathways of complement activation
alternative, lectin, classical
The spread of a pathogen is often initially countered by ...
an inflammatory response that recruits more effector cells and molecules of the innate immune system out of the blood and into the tissues, while inducing clotting in small blood vessels further downstream so that the microbe cannot spread through the circulation
When neutrophils from a patient with defects in immune cell migration into infected tissues were isolated and tested using in vitro assays for extravasation and interactions between neutrophils and endothelial cells, it was found that the neutrophils could slowly roll along the endothelial vessel wall but were unable to arrest and migrate across the endothelium. The most likely protein deficient in these neutrophils is:
an integrin (e.g. LFA-1)
_____ are soluble complement fragments that mediate localized and systemic inflammatory responses.
anaphylatoxins
You are a new member of a graduate research lab. Your research is to study the effects of a novel cytokine TNF-mu (TNF-μ). During the course of your research, you discover that TNF-μ induces monocyte maturation, inhibits eosinophil development, and begins a signaling cascade that promotes histamine release in mast cells. What term best describes the action of TNF-μ on eosinophils?
antagonistic
What is the effector molecule of humoral immunity?
antibodies
What do dendrites do?
antigen uptake, activate lymph nodes (bridge innate and adaptive)
When compared to primary humoral immune response which of these statements correctly describes B cell memory response
antigen-specific IgM antibody predominates during memory B cell responses
Influenza virus has a segmented RNA genome. Point mutations in the influenza virus genome is called ___________, which causes milder and limited disease. In contrast, antigenic changes by reassortment of the segmented RNA genome are known as __________, which causes more severe disease and higher mortality.
antigenic drift, antigenic shift
B cells, much like T cells, require 3 signals to become activated. Which option describes an event that does not occur during B cell activation
any naive Th cell (CD4 T cell) can provide the help in B cell activation as long as it is capable of producing cytokines
Where are β-defensins stored once they are made?
are packaged into lamellar bodies (see Fig. 2.6), lipid-rich secretory organelles that release their contents into the extracellular space to form a watertight lipid sheet in the epidermis and the pulmonary surfactant layer in the lung.
Receptors that are multivalent tend to bind to their ligands more strongly than receptors with a single binding site. What is the term used to describe this phenomenon?
avidity
Where does the RAG complex cut the dsDNA depicted in the figure
between the Vl and the 7 bp regions
This C3 convertase, designated C3bBb, has a special place in complement activation because...
by producing C3b, it can generate more of itself. This means that once some C3b has been formed, by whichever pathway, the alternative pathway can act as an amplification loop to increase C3b production rapidly.
Lymph nodes function as meeting points between antigen-bearing dendritic cells arriving from the tissue and recirculating B and T lymphocytes. Whereas the dendritic cells coming from the tissue enter the lymph node via the afferent lymphatic vessels, the recirculating lymphocytes enter the lymph node: A. Also from the lymph fluid draining the tissue B. Directly from their primary lymphoid organ where they develop C. From the blood by crossing the high endothelial venules D. By being trapped in the lymphoid follicle by resident macrophages E. By being carried there by dendritic cells
c
C4b2a3b
c5 convertase
Secondary/acquired immunodeficiencies:
can be brought on by numerous factors
Somatic hypermutation of V genes
can decrease the affinity of an antibody
The generation of the inflammasome leads to ________ and the expression of ________.
cell death; IL-18 and IL-1β (?)
A mutation that renders the non-classical MHC class II molecule DM nonfunctional would likely lead to
cells with class II MHC bound with CLIP
Component complements their function: C3 C1 C4b, 2a, 3b MASP C6, C7, C8, C9
central component of all 3 begins classical pathway C5 convertase initiating protease of lectin pathway MAC complex
Many of the inflammatory mediators produced by tissue macrophages at sites of infection act on the endothelial cells lining the blood vessel walls. An exception to this is (are) the:
chemokines that induce directed migration of blood monocytes
Which complement pathway would be most affected by an absence of RAG1 in developing B cells?
classical
What is C4b2a also called
classical C3 convertase
C1r associated with this pathway
classical pathway
activated by recongition of antigen-antibody complexes
classical pathway
Select the pathway that the following statements refer to (pathways can be used more than once) activated by recognition of antigen-antibody complexes uses the membrane attack complex active in C2 deficient mice activated by ficolins uses factor B involves protease activity C1r associated with this pathway
classical pathway all 3 pathways alternative pathway lectin pathway alternative pathway all 3 pathways classical pathway
A protein epitope formed as a result of three-dimensional folding of the protein, and which is destroyed if the protein denatures, is called a _______ epitope:
conformational
All of the following types of bonds are involved in receptor-ligand interaction except
covalent bond
Which of the following types of bonds would be LEAST likely in a receptor-ligand interaction?
covalent bond
All of the following are true regarding B cell development except
cross-linking of BCR at immature B cell stage by multivalent self-antigen leads to B cell maturation during development, but cross-linking of mature BCR in the periphery leads to B cell apoptosis
Antigens presented via the MHC I pathway are degraded in the
cytosol via the immunoproteasome
Bruton's XLA
defects in gene encoding Bruton's tyrosine kinases
LAD
defects in the gene LFA-1
Hematopoietic stem cells cultured in the presence of which molecule differentiate into T cells rather than B cells?
delta ligands
Which type of professional antigen-presenting cells is most likely to activate a naïve T cell?
dendritic cell
MHC I is broadly expressed on most nucleated cells while MHC II is expressed on a much narrower subset of cells which can include all of the following except
dendritic cells, macrophages, thymic epithelial cells, and B cells
In patients with lymphomas, the cancer cells invade the bone marrow and destroy the environment required for normal hematopoiesis. This leads to bone marrow failure, which disrupts the production of hematopoietic cell lineages. All of the following cell types would be affected by this except
endothelial cells
Chemokines are small chemoattractant molecules made by epithelial cells, tissue macrophages, and endothelial cells in response to infection or injury. They differ slightly in sequence and structure based on the cells that secrete them, but all of them act to recruit both monocytes and neutrophils from the blood.
false
Following TCR or BCR signaling, the most important events downstream of kinase activation are the activation of transcription factors leading to new gene expression.
false
In generating a B cell receptor gene, Vkappa segments sometimes join to Clambda segments
false
Like innate sensors of infections (TLRs, NLRs, RLRs), antibodies frequently recognize nucleic acids of pathogenic organisms.
false
MHC class I surface expression is dependent on an abundant source of pathogen-derived peptides. Thus, in uninfected cells, nearly all of the MHC class I proteins are degraded and never reach the cell surface.
false
Most eukaryotic genes are encoded in a set of exons that are brought together to form a contiguous protein coding sequence by the process of mRNA splicing. In contrast, immunoglobulin genes use somatic recombination of gene segments and not mRNA splicing to generate the final mRNA that is translated into protein.
false
Mucosal surfaces and external epithelia are major routes of pathogenic infection. Mucosal surfaces are found in tissues such as the gastrointestinal tract, the reproductive tract and the mouth and respiratory tract. While the mouth and respiratory tract are routes of virus but not bacterial infections, the gastrointestinal tract is the route for bacterial but not virus infections.
false
Our immune system efficiently kills all categories of microbes that attempt to colonize our bodies.
false
The C3 convertase amplifies the process of complement activation by generating large amounts of C3b and cleaving large numbers of C5 molecules.
false
The C3 convertase amplifies the process of complement activation by generating large amounts of C3b and cleaving large numbers of C5 molecules. (true or false)
false
The acute phase response contributes to infection control by producing molecules that promote pathogen opsonization and complement activation. This response is only induced by direct action of microbial components on hepatocytes in the liver.
false
The enzymes that cleave C3 and C4 are referred to as convertases
false
The switch in constant region use from IgM to IgD is mediated by DNA rearrangements
false
True or False: Macrophages, neutrophils, and dendritic cells (DCs) are all phagocytes. Because of this, they can present pathogen-derived protein antigens to T cells. In this regard, they are antigen-presenting cells (APCs) as well.
false
True or False: T cell receptor structure is much simpler than B cell receptor. TCR mimics the Fab region in a BCR. Therefore, TCR is completely made up of variable regions, unlike BCRs which have both variable and constant regions.
false
True or False: The antibody protein has two functional domains, one for antigen binding and a second to confer specific effector functions. The former is encoded by the light chain and the latter the heavy chain.
false
The classical and lectin pathways of complement activation converge at the step of C3 activation. However, the initiating steps of each pathway use protein components and enzymatic mechanisms that share no similarity with each other.
false The initiating steps of the classical and lectin pathways of complement activation are remarkably conserved in their mechanisms. The pathogen recognition component of the classical pathway, C1q, has structural similarity to MBL and the ficolins. The C1r and C1s components of the classical pathway, that are activated to form the serine protease, are closely related to the MASP proteins of the lectin pathway.
Acute phase proteins are proteins rapidly produced by the liver during infection, including[ff]and mannose binding lectin for examples.
ff. c-reactive protein
Once a NK have identified a target cell, it will kill by: -Granule-dependent killing involving granzyme and [gg] -[hh]-dependent killing following binding of Fas-L/Fas receptor
ff. perforin hh. death receptor
Retention of effector lymphocytes in lymphoid organs
fingolimoid
Lymph nodes function as meeting points between antigen-bearing dendritic cells arriving from the tissue and recirculating B and T lymphocytes. Whereas the dendritic cells coming from the tissue enter the lymph node via the afferent lymphatic vessels, the recirculating lymphocytes enter the lymph node:
from the blood by crossing the high endothelial venules
Anaphylatoxins produced by the complement system contribute to the inflammatory response by
functioning as chemoattractants that recruit leukocytes such as neutrophils from the blood into injured tissue, triggering mast cells degranulation, leading to the release of other inflammatory mediators, increasing binding of leukocytes to endothelial cells promoting extravasation, and stimulating macrophages to release pro-inflammatory cytokines and increase phagocytosis
Following a primary HIV infection, our immune system
generates a response that efficiently controls viral replication
All of the following is true of the common lymphoid progenitor
gives rise to T lymphocytes, gives rise to B lymphocytes, produces cell lineages that are important in adaptive immunity, and results in cell lineages that are important in innate immune responses
Which of the following HIV proteins mediates the first step of membrane fusion with target cell?
gp120
Which of the following is NOT an HIV-1 restriction factor?
gp120
The "MHC _____" refers to the complete set of HLA alleles that a person possesses on a particular chromosome 6.
haplotype
T cells selected on a b haplotype thymus would be able to respond to antigen presented on which of the following haplotype antigen presenting cells?
haplotype b and haplotype a x b
A naïve T cell refers to a T cell that:
has not yet encountered an antigen.
The five isotypes of immunoglobulin differ from each other in their:
heavy-chain constant regions
An innate immune cell has become activated by PAMP-PRR binding, leading to increased expression of several classes of molecules including enzymes. These enzymes include
iNOS
[ii] is displaced from MHC class II molecule in endosomal compartments by the proteinHLA-DM.
ii. CLIP
The enzymes of the complement system are synthesized as ...
inactive pro-enzymes, or zymogens, which become enzymatically active only after proteolytic cleavage, usually by another complement protein.
Predict the clinical outcome of a genetic defect in IRAK4, a protein required for MyD88-mediated signaling pathways
increased rates of bacterial infection
The end results of signal transduction are varied but can include
induction of cell division, cellular differentiation, altered metabolism, and altered protein secretion patterns
What is the consequence of TLR activation?
inflammation
All of the following are functions of TH1 cells EXCEPT: can contribute to autoimmunity inhibit anti-tumor responses enhance APC activity. protects against intracellular pathogens. enhance TC activity.
inhibit anti-tumor responses
Upon exposure, the __________ immune response is activated within minutes.
innate
Unlike B lymphocytes, T lymphocytes do not generate a secreted form of their antigen receptor after they are activated and proliferate. This is because the effector functions of T cells are restricted to:
interactions with other cells, such as virus-infected cells or other immune cells
What are the major cytokines that defend against viruses?
interferons - they interfere with viral replication
Who do helper T cells fight?
intracellular bacteria in phagosome
During Ig VH recombination, the processes that contribute to additional diversity at the third complementarity-determining region include ____________. (SELECT ALL THAT APPLY)
introduction of the D gene segments into the heavy-chain V gene exonuclease cleavage of the ends of the gene segments P nucleotide addition N nucleotide addition
what is a peptidoglycan?
is a polymer consisting of sugars and amino acids that forms a mesh-like layer outside the plasma membrane of most bacteria, forming the cell wall. Peptidoglycan is an alternating polymer of N-acetylglucosamine (GlcNAc) and N-acetylmuramic acid (MurNAc), strengthened by cross-linking peptide bridges
Cell membrane-destined polypeptides are translocated to the lumen of the endoplasmic reticulum, which is intriguing because the MHC class [ll] associated peptides are generated in the cytosol by [mm]. Further research revealed that presentation of cytosolic peptides is possible due to a family of ABC transporters, [nn], that mediate the ATP-dependent transport of peptides into the lumen of the endoplasmic reticulum. This transporter complex has limited specificities for the transported peptides; for example, peptides are generally [oo] amino acids in length and transport is biased in favor of hydrophobic residues at the carboxy terminus.
ll. I mm. UPS or proteasome nn. TAP1/2 oo. 8-10
When an activated conventional dendritic cell (cDC) arrives at the nearby lymph node, it has _____ phagocytic activity and _____ expression of MHC and costimulatory molecules.
low; high
Continual lymphocyte circulation is needed because:
lymphocytes have a small chance or recognizing a particular antigen.
Which of the following pairs is mismatched?
lymphocytes: innate immune response
When vesicular stomatitis virus (VSV) is used to infect mice via footpad injection, viral particles are trapped in the draining lymph node (the popliteal lymph node) within 5 minutes of injection. These viral particles are then retained in the lymph node for many hours, where they can be visualized on cells that are interacting with B cells. The cells retaining the viral particles in the lymph node are not tissue-resident dendritic cells that have migrated to the lymph node with the virus, as this process takes much longer than 5 minutes. In which region of the lymph node would you expect to find the trapped viral particles and on which cells? The virus particles are trapped on___
macrophages in the subcapsular sinus
Anaphylaxis can be triggered by cross-linking of IgE receptors on
mast cells
One of the important effects of complement activation is the assembly of the terminal components of complement to form a(n):
membrane-attack complex
Which ultimate outcome of much complement activity involving the formation of pores in the lipid bilayer membrane of microbes is pictured below?
membrane-attack complex
The production of antimicrobial peptides is one of the most evolutionary ancient mechanisms of defense for multicellular organisms, and most eukaryotic species make many different forms of these proteins. For instance, human paneth cells in the gastrointestinal epithelium make 21 different defensins. The reason for this diversity of antimicrobial peptides is:
most of them are produced only in response to infection
The mucosal tissues of the body have their own unique set of immune structures that function as sites for initiating adaptive immune responses. The necessity for mucosa-associated lymphoid tissues to have unique cell types (M cells) and structures is because:
mucosal sites, where most pathogens access the body, are exposed to vast numbers of diverse microbes
The skin and bodily secretions provide the first line of defense against infection. One response in this category that is common during upper respiratory virus infections is:
mucus production
Which property listed below is not shared by both naive B cells and T cells
multivalent antigen recognition
MHC class I deficiency
mutations in genes encoding TAP1, TAP2, or tapasin
XSCID
mutations in the gene IL2RG
Which of the following is not a mechanism of peripheral tolerance?
negative selection
Tissue resident cells at the site of infection produce cytokines and chemokines, initiating the inflammatory response. _________ are the first cells to reach the site of infection via blood circulation.
neutrophils
The second family of phagocytes comprises the granulocytes, which include:
neutrophils, eosinophils, and basophils
The enzyme iNOS generates which of the following antimicrobial molecules
nitric oxide
All of the following are examples of chemical barriers of innate immunity except:
normal microbiota
All of the following are true except the processes of immune cell adhesion, extravasation, and chemotaxis except
occurs only in the arterioles and not in venules
Toll-like receptors are located _____.
on the plasma membrane and endosomal membranes
Which statement is correct regarding immunological memory
one of the reason why elderly people do not develop adequate response to vaccination is that their existing memory cells take up most available space, out crowding the formation of new memory cells
Neutrophil defensins are
peptide antibiotics
CD4+ T cells recognize:
peptides bound to MHC Class II
In the secondary lymphoid tissue T and B cells are partitioned into discrete compartments. In the spleen, the T cell-specific compartment is called the
periarteriolar lymphoid sheath
What do neutrophils do?
phagocytosis
What does a macrophage do?
phagocytosis and recruitment of other immune cells
What are the effector functions?
phagocytosis, inflammatory response, and pathogen clearance
The process of phagocytosis is initiated when certain receptors on the surface of the cell interacts with the microbial surface. The bound pathogen is first surrounded by the phagocyte plasma membrane and then internalized in a large membrane-enclosed endocytic vesicle known as a:
phagosome
The enzyme that generates diacylglycerol (DAG) and inositol trisphosphate (IP3) from phosphatidylinositol bisphosphate (PIP2) is _____.
phospholipase C-gamma (PLCgamma)
The enzyme _________ generates diacylglycerol (DAG) and inositol trisphosphate (IP3) from phosphatidylinositol bisphosphate (PIP2).
phospholipase C-γ (PLC-γ)
Engagement of which FcR results in transport of dimeric IgA across epithelium
polyIgR
Toll-like receptors are membrane-bound pattern recognition receptors. TLR4 is found on plasma membrane. It recognizes the bacterial wall component [pp] and induces signal transduction via adapter protein MyD88. Eventually, TLR4 activation leads to the activation of transcription factor [qq].
pp. LPS qq. NF-kB
V-J recombination occurs during which phase of a B cell's development?
pre-B cell
Hyperacute graft rejection is caused by:
preformed antibodies
Which of the following is used to generate diversity in the antibody repertoire
presence of multiple variable gene segments that can be assembled into multiple different combinations, addition of N nucleotides that are not encoded in the germ line, exonuclease trimming of excess nucleotides at variable segment junctions, ability to pair a single heavy chain with different light chains so as to avoid generation of autoreactive antibodies
Some pathogenic microorganisms encode proteins such as the Staphylococcus Protein A, that bind to immunoglobulin constant region domains with high affinity. These microbial proteins provide a benefit to the microorganism by
preventing antibodies bound to the microbe from binding to Fc receptors on phagocytes
What does the central lymphatic organ do?
produce hematopic cells
Which of the following is not an outcome to PAMP binding to a PRR
proliferation
TH17 cells are involved with all of the following EXCEPT: protection against bacterial infections. inflammatory response. protection against fungal infections. protection from viral infections. autoimmunity.
protection from viral infections
When complement proteins are covalently deposited onto the surface of a bacterium, this can sometimes lead to direct lysis of the bacterium. However, more commonly, the deposition of complement proteins onto the bacterial surface does not directly harm the bacterium. Instead, these complement proteins aid in bacterial elimination by:
providing a mechanism for phagocytes bearing complement receptors to recognize and ingest the bacteria
Which statement correctly describes events during B cell development
rearrangement of the heavy chain of the BCR precedes rearrangement of the light chain during BCR development
Which of the following accounts for allelic exclusion in rearrangement within the Ig heavy chain locus
rearrangement only occurs on one gene locus at a time, and once one gene locus has successfully rearranged, expression of the other allele is prohibited
What molecules do H-FICOLIN and M-FICOLIN recognize on pathogens?
recognizes acetylated sugars such as GlcNAc and N-acetylgalactosamine (GalNAc), and particularly recognizes lipoteichoic acid, a component of the cell walls of Gram-positive bacteria that contains GalNAc.
B-cell proliferation is triggered by IL-2, IL-4, and IL-5. Each of these cytokines is secreted by activated TH cells thus their action is:
redundant
What do mast cells do?
release granules with histamine
Which effector process is not mediated by antibodies
release of cytotoxic granules containing perforins and granzymes
How are immune cells recruited into inflammation sites?
rolling adhesion, tight binding, diapedesis, and migration
cGAS-STING sense the presence of [rr] in the cytosol, leading to production of [ss](a cytokine); while RIG-I like receptor detect [tt] of viral origins.
rr. dsDNA ss. type 1 interferon tt. RNA
Epithelial surfaces provide the first line of defense against infection by the use several types of mechanisms. One of the chemical mechanisms used by epithelia is:
secretion of antimicrobial peptides by epithelial cells
Neutrophil defensins are
short peptides
Neutrophil defensins are:
short peptides
To identify genes encoding the receptors for the cytokines IL-2, IL-4, and IL-7, an siRNA screen is performed using purified T lymphocytes. To identify siRNAs that knock-down cytokine receptor expression, the T cells have been transfected with a construct that produces green fluorescent protein (GFP) when any one of these three cytokines is used to stimulate the cells. When the screen is completed, several different siRNAs have been identified that substantially reduce the T cells ability to respond to these cytokines as shown in Figure Q3.22.
siRNA-2 targets a shared subunit of all three receptors, whereas siRNA-1 and siRNA-3 do not.
How is adaptive immunity different from innate immunity?
slow acting, variable, highly selective specificity, and improve during response
Which of the following is NOT a means of generating diversity in the variable regions of the T-cell receptor genes
somatic hypermutation following activation
Which events during T cell development increases diversity of the TCR repertoire
stimulation of the CD4 and CD8 co-receptor expression, interaction of TCR-alpha chain with CD3 co-receptor after rearrangement of TCR-beta chain, proliferative of thymocytes that successfully rearranged their TCR-beta chain before they begin rearranging their TCR-alpha chain, proliferation of single positive thymocytes after they survive negative selection, pre T-alpha-chain rearrangement
MHC polymorphism at individual MHC genes appears to have been strongly selected by evolutionary pressures. In addition, the positions within the MHC protein whee most of the allelic sequence variation occurs are not randomly distributed, but are concentrated in certain regions of the MHC protein indicating that
that MHC allelic polymorphism has been driven by selection for diversity in peptide binding specificity
Which pathway of complement initiation is likely to be the one that most recently evolved?
the classical pathway The latest evolutionary development in the complement system is the classical pathway, which makes use of antibody binding to initiate complement activation. The adaptive immune system, including the production of antibodies, is only found in vertebrates.
Macrophages express multiple types of receptors on their surface that stimulate phagocytosis of microbes, leading to pathogen internalization and destruction. Many of these receptors, such as Dectin-1, rely on direct recognition of a PAMP on the pathogen surface. However, some receptors that stimulate phagocytosis rely on soluble factors (not associated with the phagocyte membrane) to identify and mark the pathogen for uptake by the phagocyte. One such receptor is:
the complement receptor
Which of the following best describes why B cell receptor requires co-receptor proteins to transduce a signal into the cell upon antigen binding
the cytoplasmic domain of the surface Ig only has three amino acids
During T cell development, successful recombination of the beta chain locus leads to expression of beta chain on the surface in conjugation with pTalpha. Signaling through this pre-TCR results in which of the following
the expression of CD4 and CD8, alpha chain recombination, and cell proliferation
The drawing in Figure Q4.12 shows antibodies bound to repetitive epitopes on the surface of a bacterial pathogen. Even though all of these epitopes are identical, not all of them have antibodies bound to them. The most likely explanation for this failure of antibodies to bind to every possible epitope on the surface of the pathogen is:
the pathogen has an immune evasion strategy due to steric antibody binding to all epitopes
Lymphocyte activation leads to robust proliferation and effector cell differentiation. The metabolic demands of these processes are met, in part, by up-regulation of glycolytic enzymes and nutrient transporters on the activated cell membrane. A key intermediate in the signaling pathway leading to enhanced glucose metabolism following antigen receptor stimulation is:
the phosphoinositide, PIP3
The first patter recognition receptor (PRR) important in innate immune responses was discovered in the fruit fly Drosophila melanogaster. Stimulation of this receptor, called Toll, induces:
the production of antimicrobial peptides
The organization of the alpha locus and the delta locus helps to ensure that each T cells cannot express both types of T cell receptors. The mechanism involved is
the rearrangement of a T cell receptor alpha gene deleted the delta locus on that allele
Which statement correctly describes the characteristics of the selection process during B cell development when compared to the selection during T cell development
the selection process during B cell development is less stringent than during T cell development, which means that B cells mostly go through positive selection, B cells only go through negative selection during development if they were rejected by positive selection for having an autoreactive BCR
Which of the following is a location where naïve TC cells could be activated to become CTLs?
the spleen
After initial complement activation by any pathway, the extent of amplification via the alternative pathway is critically dependent on what?
the stability of the C3 convertase C3bBb.
The CD1 family of non-classical MHC molecules present antigens to a number of types of T cells. All of the following are true of the CD1 family except
they are structurally similar to classical MHC II molecules
The majority of vaccines work by eliciting pathogen-specific antibodies that circulate in our bodes and protect us in the event that we are later exposed to that specific pathogen. For most viruses and bacterial toxins that we are vaccinated against, these pre-existing antibodies are protective because
they neutralize the virus or toxin, preventing it from attaching to and entering our cells
Mannose binding lectin (MBL) and ficolins are the two classes of proteins the can initiate the lectin pathway of complement activation. These proteins are selective for activating complement on the surfaces of microbial pathogens rather than host cells because
they only bind to carbohydrate side chains and oligosaccharide modifications found on pathogen surfaces but on host cell membranes
Tasmanian devils are a largely inbred population with little diversity in the MHC. Which of the following would be a likely outcome for this
they would be at higher risk of infectious disease
Naïve CD4+ and CD8+ T cells that have just finished developing leave the ______ and enter circulation.
thymus
Use the following list to complete the statements that follow: thymus; bursa of Fabricius, bone marrow; mesenteric lymph nodes. In mammals, T-cell development occurs in the _____________ , while B-cell development occurs predominantly in the _________
thymus; bone marrow
What is the main function of Clq in the immune response?
to bind to the constant, or Fc, regions of antibodies that have bound pathogens via their antigen-binding sites.
The thymic cortex has a substantial population of macrophages. Their main role is:
to engulf apoptotic thymocytes
The role of cell-mediated immunity is:
to find and eliminate cells infected with intracellular pathogens.
Hematopoiesis is a tightly regulated process and differentiation from an HSC to a mature leukocyte is coordinated by which of the following
transcription factor expression
A rabbit immunized with human IgG3 will produce antibody that reacts with all subclasses of IgG in humans
true
A single molecule of IgM can activate the C1q component of the classical complement pathway
true
All immunoglobulin molecules on the surface of a given B cell have the same idiotype.
true
Although each B cell carries two alleles encoding the immunoglobulin heavy and light chains, only one allele is expressed.
true
Antigen-presenting cells express both class I and class II MHC molecules on their cell membranes
true
Dendritic cells primarily encounter antigen in peripheral tissues, leading to activation and migration of these tissue dendritic cells to the closest lymph node to activate T cells.
true
Each family of NK cell receptors has members that promote NK cell activation, and members that send inhibitory signals when engaged. The difference between activating and inhibitory receptors lies in their association with accessory proteins that promote downstream signaling, or in their ability to recruit and activate inhibitory phosphatases, respectively.
true
For cells of the innate immune system, each individual cell has multiple pattern recognition receptors, allowing it to recognize many different pathogens. In contrast, cells of the adaptive immune system each express a unique antigen receptor that has a single specificity for pathogen recognition.
true
In the absence of an infection, most granulocytes (neutrophils, eosinophils, basophils) are found circulating in the blood, whereas other subsets of myeloid cells reside in tissues.
true
MBL has a function in the lectin pathway analogous to that of IgM in the classical pathway, and MASP-1 and MASP-2 are analogous to components in the C1 complex.
true
Many B cell epitopes are non-sequential amino acids brought together by the tertiary conformation of a protein antigen.
true
The spleen is a secondary lymphoid organ that performs several functions. In addition to its role as a site for initiating adaptive immune responses, the spleen is important in removing dead or damaged red blood cells from the circulation. Its immune function is important because blood-borne pathogens will not be transported to draining lymph nodes via the lymph fluid.
true
Neutrophils regulate the production of active cathelicidins (a class of antimicrobial peptides) by segregating the inactive propeptide from the processing enzyme that cleaves and activates it in two different types of cytoplasmic granules. These two types of granules are induced to fuse with phagosomes after ingestion of microbes, bringing the processing enzyme and the propeptide together.
true All antimicrobial peptides, including cathelicidins, are produced as inactive propeptides. The active forms of the peptides are generated following proteolytic cleavage of the propeptides. Neutrophils constitutively produce cathelicidins, which are synthesized as inactive propeptides. The inactive cathelicidin propeptides are stored in secondary granules, whereas the cleavage enzyme, neutrophil elastase, is stored in primary granules. These two types of granules are induced to fuse with phagocytic vesicles, called phagosomes, after the neutrophil has engulfed a pathogen. This fusion brings the cleavage enzyme together with the cathelicidin propeptide, leading to cathelicidin activation.
Opsonization of pathogens by both antibodies and complement proteins (C3b) leads to uptake and destruction of the pathogen by phagocytic cells that express both Fc receptors and complement receptors. Which of the following in Figure Q2.16 is the most efficient form of dual opsonization of the pathogen by antibody and C3b to maximize phagocytosis?
use figure A. The most efficient form of opsonization by antibody plus C3b is when the complement protein is covalently linked to the antibody molecule. This leads to efficient engagement of both Fc receptors and complement receptors on phagocytic cells
Patients with recurrent infections of Neisseria meningitidis, an extracellular bacterial pathogen that causes meningitis, were examined to determine the underlying cause of their immunodeficiency. A subset of these patients were found to have defects in complement activation on the bacterial surface, a process that for this bacterium is dominated by alternative complement activation leading to C3b deposition on the pathogen surface. When neutrophils from these patients were examined in vitro, the results in Figure Q2.19 were obtained.
use figure Factor P (properdin) Factor P (properdin) is made by neutrophils and stored in their granules. When neutrophils are activated by the presence of pathogens, factor P is released. Factor P binds to and stabilizes the reactive form of C3 (C3-H20) and the C3 convertase C3bBb. In the absence of factor P, the alternative complement pathway is inefficient, due to the rapid spontaneous inactivation of C3-H20 and C3bBb. This pathway is particularly important in protection against Neisseria meningitidis, and patients that are deficient in producing factor P are highly susceptible to infections with this pathogen
Infants and young children with deficiencies in specific complement components present with recurrent respiratory infections caused by extracellular bacteria. The peak age of susceptibility is between 6 and 12 months after birth. At this time, as shown in Figure Q2.12, maternal antibodies acquired by the child during fetal gestation are nearly gone, but the child is not yet generating robust antibody responses to new infections, as indicated by the low circulating levels of IgG and IgA. As children with this immunodeficiency get older, they outgrow this disease and show no further evidence of these recurrent infections. Based on this information, name one likely gene deficiency (in the complement system) that could cause this primary immunodeficiency, and the specific complement pathway likely to be affected. Explain your answer.
use figure MBL or MASP. Infants and small children with defects in MBL or MASP show recurrent upper respiratory infections by extracellular bacteria. This is due to a defect in the lectin pathway of complement activation. When maternal antibodies wane and the child is not yet generating robust antibody responses on its own, complement activation cannot proceed by the classical pathway. During this time, protection against upper respiratory bacterial infections is highly dependent on the lectin pathway, initiated by MBL or collectin binding to the pathogen. The information provided rule out the alternative pathway, which is initiated by spontaneous C3 cleavage. If there was a defect in C3, or a downstream component of the complement cascade shared by all three pathways, the recurrent infections would not disappear as children age
Adaptive immune responses are slow to develop, taking days to weeks after exposure to reach their peak. However, these responses are more specific than innate responses, and also generate immunological memory. These latter features, which provide enhanced protection upon re-infection with the same pathogen, are the basis of
vaccines
Adaptive immune responses are slow to develop, taking weeks after exposure to reach their peak. However, these responses are more specific than innate responses, and also generate immunological memory. These latter features, which provide enhanced protection upon re-infection with the same pathogen, are the basis of
vaccines
Antibodies, complement proteins, and phagocytic cells provide effective protection against all of the following types of infections in the figure below, except ________ [PICTURE]
virus-infected cell
Vaccination against many infectious diseases has provided enormous benefit in developed countries, leading to the virtual eradication of diseases such as polio, measles, smallpox, and others. However, efforts to create long-lasting vaccines against some viral infections, like influenza and HIV, have not been successful to date because:
viruses like HIV and influenza undergo antigenic variation to evade previous immune responses
Who do complements fight?
viruses, parasites, and intracellular bacteria in phagosome
Which factors do not directly influence the types of polarizing cytokines that direct Th cell differentiation
whether this pathogen had previously infected the host
How are α-defensins made?
α-defensin is made by neurophils. Oncce made they are stored in the PRIMARY GRANULES of Neutrophils.
How are β-defensins made?
β-defensins are made by epithelia outside the gut, primarily in the respiratory and urogenital tracts, skin, and tongue. Specifically by keratinocytes in the epidermis and by type II pneumocytes in the lungs
Indicate whether each of the following statements is true or false. If you believe a statement is false, explain why: A) Cytokines can regulate which branch of the immune system is activated. B) Both CTLs and NK cells release perforin after interacting with target cells. C) Activation of naïve CTL-Ps requires a co-stimulatory signal delivered by interaction of CD28 and CD80/86 D) CTLs use a single mechanism to kill target cells. E) CD4+ T cells are absolutely require for the activation of naïve CD8+ T cells F) The ability of an NK cell to kill a target cell is determined by signals received through both activating and inhibiting receptors G) Human NK cells express functional Ly49 receptors H) NK cells must express inhibitory receptors for self-MHC class I proteins in order to develop the capacity to kill altered-self cells.
(A) True. (B) True. (C) True. (D) False. There are two pathways by which cytotoxic T cells kill target cells. One pathway is perforin (E) False. Naïve CD8 T cells can be activated in the absence of CD4 T-cell help. T-cell help, however, is required for optimal proliferation and memory generation. (F) True. (G) False. Ly49 receptors are found on murine cells. Human NK cells express KIR receptors
Indicate whether each of the properties listed below is exhibited by either NK cells, CTLs, NKT cells, All (of these cell populations), or None (of these cell populations). Note, not all cells in the population have to have the property to list them in your answer. A. Can make IFN B. Can make IL-2 C. MHC Class I restricted D. Express CD8 E. Cytotoxic capability F. Express NK1.1 G. Express CD4 H. Express CD3 I.Recognize lipids J.Can express the IL-2 receptor K. Express T cell receptor L. Respond only to soluble antigens M. Produce perforin N. Express FasL
(a) All. (b) All. (c) CTL. (d) CTL. (e) All. (f) Some NK and NKT. (g) Some NKT. (h) CTL and NKT. (i) NKT. (j) All. (k) CTL and NKT. (l) None. (m) All. (n) Some CTLs.
The following sentences are all false. Identify the error(s) in each sentence and correct the sentences to be true. A) Macrophages activate naïve T cells better than dendritic cells B) ICOS enhances T-cell activation and is called a co-inhibitory C) Virtually all cells in the body express co-stimulatory ligands D) CD28 is the only co-stimulatory receptor that binds to B7 family members E) Signal 3 is provided by negative co-stimulatory receptors. F) CD4+ T cells interact with MHC class I on CD8+ T cells G) Naïve T cells produce IFN- H) T-Bet and GATA-3 are effector cytokines I)Polarizing cytokines are produced only by APCs J) Bcl-6 is involved in the delivery of co-stimulatory signals K) TH17 and TFH cells subsets are the major sources of B-cell help L) pTREG cells enhance inflammatory disease M) Effector cytokines act exclusively on T cells N) Central memory T cells tend to reside at the site of infection O) Like naïve T cells, effector memory cells express CCR7
(a) Dendritic cells are best at activating naïve T cells— they express a high density of co-stimulatory ligands and MHC molecules. (b) ICOS is a positive co-stimulatory receptor (it is expressed on some effector T cells, including TFH cells). (c) Most cells do not express co-stimulatory ligands. Professional APCs (and thymic epithelial cells) are among the only cells that do. (d) ICOS and CTLA-4 also bind B7 family members (CD80 and CD86). PD1 also binds a B7 like molecule, PD-L1. (e) Signal 3 is provided by cytokines, which include the polarizing cytokines that induce helper T-cell lineage differentiation. (f) They do not have any receptor forMHC class I and do not interact directly with CD8 T cells via their TCRs, which bind to MHC class II. (g). Naïve T cells produce IFN-gamma. (h) They are master transcriptional regulators ofT helper cell lineage differentiation. (i) APCs can make some polarizing cytokines, but many of these cytokines originate from other cells, including other T cells, B cells, mast cells, and NK cells. (j) T-bet is a master transcriptional regulator of TFH lineage differentiation. (k) TFH and TH2 are classically the major sources of B-cell help, although all helper subsets can interact with B cells and influence Ig class switching. (l) They inhibit T-cell activation. (m) Effector cytokines have many different cellular targets, including B cells, endothelial cells, stromal cells in tissues, innate immune cells, and so on, as well as other T cells. (n) Central memory cells tend to reside in secondary lymphoid organs. (o) CCR7 attracts cells to secondary lymphoid tissue, and effector cells tend to rove the periphery. They typically downregulate CCR7.
Indicate whether each of the following statements regarding Fas-mediated, or perforin-mediated programmed cell death is true of false. If you believe a statement is false, explain why. A) Both mechanisms induce apoptosis in target cells B) Target cells must express FasL to be killed via the Fas-mediated pathway C) Only the perforin mediated pathway stimulates a caspase cascade. D) Both pathways require granzyme to induce apoptosis E) Both pathways lead to the activation of caspase-3 F) Granzyme is responsible for the assembly of membrane pores
(a) True. (b) False. They need to express Fas, which transmits the pro-apoptotic signal. (c) False. Both mechanisms induce caspase activation. (d) False. Only the perforin-mediated pathway depends on granzyme activity. (e) True. (f) False. Perforin is responsible for the development of surface membrane and endocytic membrane pores.
Like TH1 and TH2 cells, TH17 cells and TREG cells cross-regulate each other. Which of these two statements about this cross-regulation is/are true? Correct the statement, if false. A. TGF- is a polarizing cytokine that stimulates up-regulation of each of the master transcriptional regulators that polarize T cells to the TH17 and TREG lineages B. IL-6 inhibits polarization to the TREG lineage by inhibiting expression of RORT
(a) True. It stimulates production of both FoxP3 and ROR gamma. (b) False. IL-6 in combination with TGF-beta polarizes cells to the TH17 lineage, an event that requires ROR gamma. IL-6 acts in part by inhibiting expression of FoxP3.
A virus enters a cut in the skin of a mouse and infects dendritic cells, stimulating a variety of PRRs both on and within the dendritic cells that induce them to produce IL-12. The mouse subsequently mounts an immune response that successfully clears the infection. Which of the following statements are likely to be true about the immune response that occurred? Correct any statements that are false to make them true. A) The infected dendritic cells up-regulated CD80/CD86 and MHC Class II B) The dendritic cells encountered and activated naïve T cells in the skin of the mouse C) Naïve T cells activated by these dendritic cells generated signals that release internal Ca2+ stores D) Naïve T cells activated these dendritic cells were polarized to the TH2 lineage. E) Only effector memory T cells were made in this mouse
(a) Very likely. Any activated professional APC, like a dendritic cell, up-regulates MHC molecules and co-stimulatory ligands, making them ideal activators of T cells. (b) Very unlikely. Activated dendritic cells travel to the draining lymph nodes (or spleen) and encounter naïve T cells there, not in peripheral tissues. Naïve T cells travel among secondary lymphoid organs, not peripheral tissues. However, effector T cells and some memory T cells, do travel to peripheral tissues and can be activated by dendritic cells there. (c) Very likely. TCR stimulation rapidly induces Ca2+ mobilization. (d) Very unlikely. The virus induced dendritic cells to make IL-12, one of the central polarizing cytokines for the TH1 lineage. (e) Very unlikely. Central memory cells were certainly generated, too.
Which of the following statements is TRUE of lysozyme?
.Lysozyme splits peptidoglycan
CD8 positive T cells recognize their antigen presented by which molecules?
.MHC Class I
Which of the following statements is NOT true?
.T-cell receptor α and β chains pair together, but the α chain can be switched out for a γ or a δ chain.
Match the definition with the term: 1. The binding of a monovalent Fab fragment to one binding site on an antigen 2. Bonus effect of multivalent binding, result in "stronger" binding
1. Affinity 2. Avidity
What are the 2 ways the ALTERNATE PATHWAY can be activated?
1. By the action of the lectin or classical pathway. C3b generated by either of these pathways and covalently linked to a microbial surface can bind factor B. This alters the conformation of factor B, enabling a plasma enzyme called factor D to cleave it into Ba and Bb. Bb remains stably associated with C3b, forming the C3bBb C3 convertase. 2. The second way of activating the alternative pathway involves the spontaneous hydrolysis of the thioester bond in C3 to form C3(H2O). This C3(H2O) can bind factor B, which is then cleaved by factor D, producing a short-lived fluid-phase C3 convertase, C3(H2O)Bb. Although formed in only small amounts by C3 tickover, fluid-phase C3(H2O)Bb can cleave many molecules of C3 to C3a and C3b. Much of this C3b is inactivated by hydrolysis, but some attaches to the surfaces of any microbes present. C3b formed in this way is no different from C3b produced by the lectin or classical pathways and binds factor B, leading to the formation of C3 convertase and a stepping up of C3b production.
2 ways COMMENSAL BACTERIA help keep pathogens at bay?
1. COMMENSAL BACTERIA can make antimicrobial substances such as lactic acid and Antimicrobial peptides. 2. Commensal microorganisms also induce responses that help to strengthen the barrier functions of epithelia by stimulating the epithelial cells to produce antimicrobial peptides.
What are the 3 pathways of COMPLEMENT ACTIVATION?
1. Classical pathway of complement activation. This pathway is antibody triggered. 2. ALTERNATIVE PATHWAY of complement activation, which can be activated by the presence of the pathogen alone. 3. LECTIN PATHWAY of the complement activation, which is activated by lectin-type proteins that recognize and bind to carbohydrates on pathogen surfaces.
What are the different ways C1 binds to pathogens?
1. Clq component binds to antibodies that have bound to pathogens 2. Clq can also bind directly to the surface components of some bacteria pathogens. 3.By binding to C-reactive protein, an acute-phase protein in human plasma that binds to phosphocholine residues in bacterial surface molecules.
What are the 2 ways CONVERTASE formation can be prevented?
1. Convertase formation can be prevented by cleaving C3b to an inactive derivative, iC3b. 2. By having , a membrane-attached protein known as decay-accelerating factor (DAF or CD55) competes with factor B for binding to C3b on the cell surface and can displace Bb from a con- vertase that has already formed.
What are 3 important classes of antimicrobial peptides.
1. Defensins 2. Cathelicidins 3. Histatins
What is the difference between GRAM-POSITIVE bacteria and GRAM-NEGATIVE bacteria
1. In Gram-positive bacteria (upper left panel), peptidoglycan forms the outer layer in which other molecules are embedded such as teichoic acid and the lipoteichoic acids that link the peptidoglycan layer to the bacterial cell membrane itself. 2.. In Gram-negative bacteria (upper right panel), a thin inner wall of peptidoglycan is covered by an outer lipid membrane that contains proteins and lipopolysaccharide (LPS). Lipopolysaccharide is composed of a lipid, lipid A (turquoise circles), to which is attached a polysaccharide core (small turquoise hexagons).
2 places where are the inactive Cathelicidins propeptides stored
1. In neutrophils, the inactive cathelicidin propeptides are stored in another type of specialized cytoplasmic granule called SECONDARY GRANULES. 2.In keratinocytes, cathelicidins, like β-defensins, are stored and processed in the lamellar bodies.
Name 2 antibacterial enzymes that attack the chemical features specific to bacterial cell walls?
1. Lysozymes 2. Secretory Phospholipase A2 They are secreted in tears and saliva and by phagocytes.
What are the 4 PATHOGEN RECOGNITION RECEPTORS (PRRs) that can trigger the LECTIN PATHWAY?
1. MANNOSE-BINDING LECTIN (MBL) (liver) 2. L-FICOLIN (liver) 3. M-FICOLIN (lungs/blood cells) 4. H-FICOLIN (liver)
Match the enzyme with its function 1. Artemis 2. Rag1/2 3. MASP2 4. TdT
1. Nuclease activity to open the DNA hairpin and generate P-nucleotides 2. Recognize RSS and create single stranded break 3. Associate with MBL and cleave C4 4. Non-template addition of N-nucleotides
The mammalian immune response to invading organisms proceeds in three phases. what are they?
1. The first begins with the immediate innate defenses. The first phase of host defense consists of those mechanisms that are present and ready to resist an invader at any time. 2. Then with the induced innate defensins 3. Finally with the adaptive immunity.
RIG-I like receptors (RLRs) such as RIG-I, MDA-5, and STING are cytoplasmic nucleic acid sensors. Give two examples of how such innate sensors distinguish between the RNA/DNA of the host from that of an infecting pathogen.
1. Unique structure: RIG-I recognizes single-stranded RNA that lacks the 5′-cap structure found on mammalian mRNA. A second example is MDA-5, which recognizes double-stranded RNA, a form of RNA not generally found in healthy host cells. A third example is STING, which recognizes cyclic dinucleotides made by bacteria, but not by host cells. 2. Localization: Innate DNA sensors recognize double-stranded DNA found in the cytosol; in contrast, host DNA is generally localized to the nucleus. An example is cGAS, which binds to cytosolic DNA and stimulates the production of cyclic GMP-AMP (cGAMP) that, in turn, activates STING.
What does Activated MASP-2 do to C4 and C2?
1. When MASP-2 cleaves C4, it releases C4a, allowing a conformational change in C4b that exposes the reactive thioester. 2. Then, C4b bonds covalently via this thioester to the microbial surface nearby, where it then binds one molecule of C2. 3. C2 is then cleaved by MASP-2, producing C2a, that remains bound to C4b to form C4b2a, which is the C3 convertase of the lectin pathway. 4. C4b2a now cleaves many molecules of C3 into C3a and C3b. The C3b fragments bond covalently to the nearby pathogen surface, and the released C3a initiates a local inflammatory response. The complement-activation pathway initiated by ficolins proceeds like the MBL lectin pathway.
What are the 3 subtypes of defensins
1. defensin α- 2. defensin β- 3. defensin θ- They are distinguished on the basis of amino acid sequence, and each subtype has members with distinct activities. Some being active against Gram-positive bacteria and some against Gram-negative bacteria, while others are specific for fungal pathogens.
1.43 Synthesis question: The immune system uses several types of effector modules to protect us against different categories of pathogens. Four major types of pathogens are shown in Figure Q1.43. a) Which of these categories might be effectively eliminated by innate immune responses that include antimicrobial peptides and phagocytic cells such as neutrophils and macrophages? Explain your answer. b) Which of these categories of pathogenic organisms might be most effectively dealt with by antibodies, if the innate response is insufficient for their eradication? c) Which of these categories of pathogenic organisms would require T lymphocyte responses for their elimination? PICTURE ON LAPTOP
1.43: a) Extracellular bacteria and fungi. These pathogenic microbes are often efficiently cleared by the innate immune response. The pathogens express PAMPs that stimulate PRR on innate cells in the infected tissue, such as macrophages and dendritic cells. These activated macrophages and dendritic cells induce an inflammatory response. The inflammatory response leads to the influx of fluid and phagocytic cells into the site of infection. The fluid contains some preexisting antibodies and complement proteins, that will 'tag' the microbes. The inflammatory response also recruits neutrophils and monocytes from the blood, which will phagocytose and destroy the bacteria or fungi. In many cases, this response is sufficient to eliminate the infection, without the necessity for an adaptive immune response. b) Extracellular bacteria and fungi; helminthic parasites. These extracellular pathogens will elicit antibody responses, if they are able to avoid clearance by innate immune responses. Antibodies will coat the pathogens, leading to activation of innate immune cells that ultimately do the 'dirty work' of eliminating the pathogen. In the case of extracellular bacteria and fungi, the antibody-coated microbes are readily engulfed by phagocytic cells and destroyed. In the case of helminthic parasites, antibody-coated parasites will elicit activation of basophils and eosinophils that deposit toxic compounds onto the parasite surface. c) Viruses; intracellular bacteria and protozoa. Microbes that replicate inside host cells cannot be eliminated by antibody-dependent mechanisms. Instead, T cells are required for eradicating these infections. In the case of viruses, cytotoxic T cells will recognize and kill virus-infected cells. In the case of intracellular bacteria and protozoa, these microbes generally infect and replicate in macrophages. Their elimination is dependent on CD4 T cells that will activate the infected macrophage to up-regulate multiple microbicidal mechanisms for killing the intracellular pathogen.
Which of the following occurs when macrophages become activated after phagocytosing a pathogen? 1. Presentation of peptides from the pathogen on MHC class I molecules 2. Secretion of inflammatory mediators to recruit and activate T cells and neutrophils 3. Direct activation of B cells by macrophages 4. An increase in co-stimulatory molecules for interacting with T cells
2 and 4 only
Opsonization of pathogens by both antibodies and complement proteins (C3b) leads to uptake and destruction of the pathogen by phagocytic cells that express both Fc receptors and complement receptors. Which of the following in Figure Q2.16 is the most efficient form of dual opsonization of the pathogen by antibody and C3b to maximize phagocytosis
2.16 chapter 2 questions
Match the definition with the term: 20. the binding of a monovalent Fab fragment to one binding site on an antigen 21. bonus effect of multivalent binding, result in "stronger" binding A. Avidity B. Magnetism C. Valency D. Affinity E. Antigen
20: D 21: A
Match the enzyme with its function 22. Artemis 23. Rag1/2 24. MASP2 25. TdT A. Non-template addition of N-nucleotides B. Nuclease activity to open the DNA hairpin and generate P-nucleotides C. Recognize RSS and create single stranded break D. Phosphorylate IB E. Associate with MBL and cleave C4
22: B 23: C 24: E 25: A
What length must the RSS spacer be to link the above V segment to a downstream J segment
23 bp
Using only random VDJ recombination, from 40 V, 23 D, and 6 J gene segments, what are the # of possible variable regions of an antigen receptor molecule?
5520
How many complementarity-determining regions (CDRs) contribute to the antigen/MHC-binding site in an intact T-cell receptor?
6
How many complementarity-determining regions contribute to the antigen/MHC-binding site in an intact T-cell receptor?
6
In a heterozygous individual, what is the maximum # of different MHC I molecules that an epithelial cell normally expresses at its surface?
6
Using only random VDJ recombination, from 40 V, 25D, and 6 J gene segments, what are the number of possible variable regions of an antigen receptor molecule?
6000
Adaptive immune responses are slow to develop, taking days to weeks after exposure to reach their peak. However, these responses are more specific than innate responses, and also generate immunological memory. These latter features, which provide enhanced protection upon re-infection with the same pathogen, are the basis of: A. Vaccines B. Antibiotics C. Systemic shock D. Complement activation E. Phagocytosis
A
B cells express a complement receptor that binds to C3b cleavage products, such as iC3b and C3dg. When a B cell with an antigen receptor that specifically recognizes that pathogen also has its complement receptor stimulated because the pathogen is opsonized with these C3 fragments, B cell activation is greatly enhanced. Due to this mechanism, B cells can be activated by much lower concentrations of antigen (in this case, the pathogen) than if the antigen is devoid of complement components. This mechanism functions to: A. Ensure that pathogens are readily detected by the adaptive immune system before they replicate to high levels in the host B. Prevent B cells from being activated in response to antigens that are not pathogens C. Allow B cells to phagocytose the pathogen and help destroy it D. Induce increased rounds of B cell replication to make more pathogen-specific B cells E. Allow the B cell to block pathogen replication by interfering with multiple pathogen surface functions
A
Chemokines such as CXCL8 have a key role in the rapid recruitment of neutrophils to the site in the tissue containing the focus of an infection. In this response, CXCL8 has two different functions. In addition to inducing integrin activation on the neutrophil, CXCL8 also functions to: A. Induce directional migration of the neutrophil in the tissue B. Induce increased expression of P-selectin and E-selectin on the endothelium C. Induce increased expression of integrins on the neutrophil surface D. Induce blood vessel dilation and fluid leakage into the infected tissue E. Induce increased phagocytic activity by the neutrophil
A
Multiple choice: Although the complement cascade can be initiated by antibodies bound to the surface of a pathogen, complement activation is generally considered to be an innate immune response. This is because: A. Two of the three pathways for complement activation are initiated by constitutively produced recognition molecules that directly interact with microbial surfaces. B. When the complement cascade leads to the formation of a membrane-attack complex, the pathogen is killed. C. Several of the soluble products generated by complement activation lead promote the inflammatory response. D. Complement proteins bound to the pathogen promote uptake and destruction by phagocytic cells. E. The C3 convertase is only produced when complement activation is initiated by antibody binding to a pathogen.
A
Multiple choice: When macrophages in a tissue encounter bacteria, they release cytokines that induce an inflammatory response. These cytokines act on other immune cells, to recruit them to the site of infection and to enhance their activities. In addition, these cytokines act on the endothelial cells of the blood vessel wall to: A. Increase their permeability, allowing fluid and proteins to leak into the tissue B. Solidify the tight junctions to prevent the bacteria from entering the blood C. Proliferate, allowing the blood vessel to enlarge D. Up-regulate microbicidal mechanisms, so they can kill bacteria E. Secrete anti-microbial peptides
A
NK cells can be activated following recognition of a virus-infected cell, if that cell has down-regulated expression of MHC class I proteins on its surface. However, NK cells can also recognize infected cells or tumor cells, even if they still express MHC class I proteins. In this latter case, activating receptors on NK cells are recognizing: A. Molecules on the target cell up-regulated by cellular or metabolic stress B. Cytokines secreted by the virus-infected or tumor cell C. MHC class I-like decoy molecules encoded by the virus D. Mutated self-proteins expressed by the tumor cell E. Double-stranded DNA in the cytoplasm of the infected or tumor cell
A
One surprising aspect of the immune system is that individuals make responses to human tissues from a different individual, causing serious problems for organ and tissue transplantation. The basis for this immune response is: A. The extensive polymorphism of MHC genes in the human population B. The fact that transplanted tissues often carry infectious microbes into the recipient C. The fact that individuals may differ in their blood group antigens (i.e., their blood type) D. The presence of many antigen-presenting-cells in the transplanted tissue E. The presence of many B and T lymphocytes in the transplanted tissue
A
Opsonization of pathogens by both antibodies and complement proteins (C3b) leads to uptake and destruction of the pathogen by phagocytic cells that express both Fc receptors and complement receptors. Which of the following in Figure Q2.16 is the most efficient form of dual opsonization of the pathogen by antibody and C3b to maximize phagocytosis?
A
Septic shock is a serious, often fatal response to an infection in the bloodstream. This response can be elicited in mice by intravenous injection of bacterial LPS. However, it was found that one strain of mice, C3H/HeJ, is resistant to LPS-induced shock. This fact was used to clone the gene for TLR-4 based on positional cloning from C3H/HeJ mice. Another example of a strain of mice that is resistant to LPS-induced septic shock is: A. TNF-receptor-deficient mice B. TLR-2-deficient mice. C. LFA-1-deficient mice D. Neutrophil-deficient mice E. Complement receptor-deficient mice
A
Signaling through the Drosophila Toll pathway is initiated when pathogen recognition receptors (PRRs) bind to microbial products, such as bacterial peptidoglycan. Aspects of this pathway share similarity to the mammalian complement cascade as well as to the innate recognition system based on TLRs. One feature of Toll signaling that resembles the complement pathway is: A. The activation of an extracellular proteolytic cascade involving cleavage of self-proteins B. The deposition of Toll signaling proteins onto the microbial surface C. The release of soluble fragments of Toll that induce inflammation D. The assembly of a membrane attack complex in the microbial membrane following Toll activation E. The presence of receptors for Toll cleavage products on phagocytic cells to promote pathogen ingestion
A
Stimulation of the nucleic acid sensing TLRs that reside in endosomal membranes induces the production of a different cytokine response than is produced by stimulation of the plasma membrane TLRs. In part, this distinction is based on the different adapter proteins used by the nucleic acid sensing TLRs, leading to the activation of IRF factors. The cytokine response following stimulation of nucleic acid- sensing TLRs is characterized by production of: A. The antiviral cytokine, type I interferon B. TNF-, which induces increased vascular permeability C. Antimicrobial peptides by macrophages D. Chemokines that recruit neutrophils E. The inflammatory complement fragments, C3a and C5a
A
The importance of complement activation as an innate immune defense against infections is illustrated by: A. The evolution of complement avoidance strategies by many pathogens B. The large number of proteins involved in the complement pathway C. The large number of complement regulatory pathways expressed by the host D. The existence of three different mechanisms for initiating complement activation E. The ability of the membrane attack complex to lyse some pathogens
A
The pattern recognition receptors on cells of the innate immune system are genetically encoded, meaning that their sequences and specificities are determined prior to the development of the individual. In contrast, the antigen receptors of B and T lymphocytes arise from a random rearrangement process that occurs differently in each lymphocyte as it develops. One potential problem entailed by the random process that generates lymphocyte antigen receptors is the possibility that: A. Some antigen receptors might recognize the individuals on cells or antigens B. Many lymphocytes might generate antigen receptors that don't recognize anything C. Many lymphocytes might generate antigen receptors that recognize multiple different pathogens D. Some antigen receptors might recognize foreign tissues and lead to graft rejection during organ transplantation E. Some lymphocytes might not generate functional antigen receptor proteins
A
he majority of vaccines work by eliciting pathogen-specific antibodies that circulate in our bodies and protect us in the event that we are later exposed to that specific pathogen. For most viruses and bacterial toxins that we are vaccinated against, these pre-existing antibodies are protective because: A. They neutralize the virus or toxin, preventing it from attaching to and entering our cells. B. They bind to the virus or toxin and carry it to the liver where it can be degraded. C. They bind to the virus or toxin and directly induce lysis. D. They induce mucus production that helps flush the toxin or virus out of the body. E. They bind to epithelial cells and induce the production of antimicrobial peptides.
A
Matching: The diagram in Figure Q6.1 shows a pathogen (in red) that is present in different cellular compartments of each of the cell types shown. In each case, a specific T cell subset will recognize peptides of that pathogen presented on MHC molecules on the surface of the cell, and will execute its effector function. From the list below, match the appropriate T cell effector response to the cell type and location of the pathogen. (SEE IMAGE)
A = ii B= v C = iii
In mice that lack both MHC class I and class II in the thymus, T-cell development will show:
A block in the T-cell development at the CD4+/CD8+ double positive stage
What happens when MANNOSE-BINDING LECTIN (MBL) binds to pathogens?
A conformational change occurs in MASP-1 that enables it to cleave and activate a MASP-2 molecule in the same MBL complex. Then Activated MASP-2 can cleave the complement components C4 and C2
CXCR5 is the receptor for the chemokine CXCL13, secreted by follicular stromal cells and follicular dendritic cells in the B cell zones (i.e., lymphoid follicles) of secondary lymphoid organs. If the CXCR5 gene is disrupted in all T cells but remains fully functional in all other cell types, the individual would have:
A defect in T cell-dependent antibody responses
The T-cell receptor (TCR)for antigen is:
A heterodimer
What are PHOSPHOLIPASE A2 and what do they do?
A highly basic enzyme that can enter the bacterial cell wall to access and hydrolyze phospholipids in the cell membrane, killing the bacteria.
Genetic deficiencies have been described in patients for complement components C3, C4 and C6. The lack of which component can lead to particularly severe consequences? Give a brief explanation.
A lack of C3 in a patent would cause the patient to have severe consequences. The patient would be hindered in the ability for opsonization and in the formation of MAC. This means that if the patient had a deficiency in C3, he or she would have recurrent bacterial infections. Furthermore, the patient may have immune-complex diseases because of the lack of C3.
what is a phagosome?
A membrane-bound vesicle in a phagocyte containing the phagocytized material.
What must happen for pathogen to establish infection?
A microorganism must first invade the body by binding to or crossing an epithelium.
Disease occurs when...
A microorganism succeeds in evading or overwhelming innate host defenses to establish a local site of infection, and then replicates there to allow its further transmission within our bodies.
MHC class II molecules expressed on the surface of thymic cortical epithelial cells normally have a wide repertoire of different peptides bound to them. By engineering a construct that fuses the MHC class II protein to a single peptide sequence, and expressing this construct in thymic cortical epithelial cells that have their endogenous MHC class II genes knocked out, it is possible to generate a mouse line where all MHC class II proteins expressed on all thymic cortical epithelial cells are bound to the same peptide. These mice are often referred to as 'single-peptide' mice. Examination of the T cell developing in these single peptide mice would likely show:
A significant reduction in the numbers of mature CD4 T cells
How do self-antigens that are specific to tissues away from the thymus (like insulin or keratin for example) get in the thymus so that developing T cells that react to them can be deleted?
A transcription factor, AIRE is expressed in thymic medullary epithelial cells, which allows these cells to express proteins normally found in other tissues.
Signaling through the Drosophila Toll pathway is initiated when pathogen recognition receptors (PRRs) bind to microbial products, such as bacterial peptidoglycan. Aspects of this pathway share similarity to the mammalian complement cascade as well as to the innate recognition system based on TLRs. One feature of Toll signaling that resembles the complement pathway is: A. The activation of an extracellular proteolytic cascade involving cleavage of self-proteins B. The deposition of Toll signaling proteins onto the microbial surface C. The release of soluble fragments of Toll that induce inflammation D. The assembly of a membrane attack complex in the microbial membrane following Toll activation E. The presence of receptors for Toll cleavage products on phagocytic cells to promote pathogen ingestion
A. Like the complement cascade in mammals, Toll signaling is initiated by pathogen recognition receptors that activate the first step of a proteolytic cascade following recognition of microbial products. This extracellular proteolytic cascade ultimately ends with the cleavage of the Drosophila protein Spätzle. Cleavage of Spätzle changes its conformation, enabling it to bind to Toll and induce Toll dimerization, thereby initiating Toll signaling.
NK cells can be activated following recognition of a virus-infected cell, if that cell has down-regulated expression of MHC class I proteins on its surface. However, NK cells can also recognize infected cells or tumor cells, even if they still express MHC class I proteins. In this latter case, activating receptors on NK cells are recognizing: A. Molecules on the target cell up-regulated by cellular or metabolic stress B. Cytokines secreted by the virus-infected or tumor cell C. MHC class I-like decoy molecules encoded by the virus D. Mutated self-proteins expressed by the tumor cell E. Double-stranded DNA in the cytoplasm of the infected or tumor cell
A. One important receptor on NK cells is NKG2D, which forms a homodimer on the NK cell surface. This activating receptor binds to ligands that are MHC class I-like molecules induced by various types of cellular stress. For example, the ligands for NKG2D are expressed in response to cellular or metabolic stress, and so are up-regulated on cells infected with intracellular bacteria and most viruses, as well as on incipient tumor cells that have become malignantly transformed. Thus, recognition by NKG2D acts as a generalized 'danger' signal to the immune system.
Septic shock is a serious, often fatal response to an infection in the bloodstream. This response can be elicited in mice by intravenous injection of bacterial LPS. However, it was found that one strain of mice, C3H/HeJ, is resistant to LPS-induced shock. This fact was used to clone the gene for TLR-4 based on positional cloning from C3H/HeJ mice. Another example of a strain of mice that is resistant to LPS-induced septic shock is: A. TNF-receptor-deficient mice B. TLR-2-deficient mice. C. LFA-1-deficient mice D. Neutrophil-deficient mice E. Complement receptor-deficient mice
A. Septic shock is caused by a massive release of TNF-α into the bloodstream, which causes systemic vasodilation leading to a loss of blood pressure, and increased vascular permeability, which leads to a loss of plasma volume. TNF-α also causes blood clotting in small vessels throughout the body, leading to compromised blood perfusion of many organs and thus to organ failure. Mice with defects in TNF-α receptors or in which the ADAM17 gene (encoding TACE, the TNF-α-converting enzyme) has been inactivated in myeloid cells, are resistant to septic shock. TACE is needed to release TNF-α from the cell membrane of myeloid cells, generating soluble TNF-α that enters the bloodstream.
When stimulated by binding to bacterial products, the fMet-Leu-Phe (fMLF) receptor triggers multiple responses by phagocytes, including migration and induction of antimicrobial activities. Most of these responses are activated by small GTPases of the Rac and Rho families that are indirectly activated by fMLF receptor stimulation. The fMLF receptor can initiate multiple downstream signaling pathways because: A. It couples to a heterotrimeric G protein that has α and βγ subunits with independent activities. B. It couples directly to two different guanine nucleotide exchange factors (GEFs). C. It binds to Rac, Rho, and cdc42 directly. D. It promotes fusion of phagosomes with lysosomes, initiating multiple signals. E. It induces assembly of multiple enzymes from individual cytosolic components.
A. Signaling by the fMLF receptor induces cell motility, metabolism, gene expression, and cell division through activation of several Rac and Rho family small GTPase proteins. To accomplish this, the fMLF receptor, a member of the G-protein-coupled receptor family, activates a heterotrimeric G protein consisting of Gα, Gβ, and Gγ subunits. After receptor stimulation, the heterotrimeric G protein undergoes a conformational change, leading to the exchange of GDP for GTP by the Gα subunit. This causes dissociation of the trimer into two components, Gα and Gβγ, each of which has separate activities. The α subunit of the activated G protein indirectly activates Rac and Rho, while the βγ subunit indirectly activates the small GTPase Cdc42. Activation of these small GTPases is dependent on the activation of guanine nucleotide exchange factors (GEFs), one for each specific GTPase.
Stimulation of the nucleic acid sensing TLRs that reside in endosomal membranes induces the production of a different cytokine response than is produced by stimulation of the plasma membrane TLRs. In part, this distinction is based on the different adapter proteins used by the nucleic acid sensing TLRs, leading to the activation of IRF factors. The cytokine response following stimulation of nucleic acid-sensing TLRs is characterized by production of: A. The antiviral cytokine, type I interferon B. TNF-α, which induces increased vascular permeability C. Antimicrobial peptides by macrophages D. Chemokines that recruit neutrophils E. The inflammatory complement fragments, C3a and C5a
A. The nucleic acid sensing TLRs, such as TLR-3 and TLR-7, induce the activation of IRF transcription factors, leading to the secretion of antiviral type I interferons. Each of these two endosomal receptors uses a distinct signaling pathway, starting with the binding of distinct adapter proteins to induce IRF factor phosphorylation. However, consistent with their importance in innate responses to virus infections, these TLRs both induce transcription of type I interferon genes when they are stimulated.
1.33 Multiple choice: The majority of vaccines work by eliciting pathogen-specific antibodies that circulate in our bodies and protect us in the event that we are later exposed to that specific pathogen. For most viruses and bacterial toxins that we are vaccinated against, these pre-existing antibodies are protective because: A. They neutralize the virus or toxin, preventing it from attaching to and entering our cells. B. They bind to the virus or toxin and carry it to the liver where it can be degraded. C. They bind to the virus or toxin and directly induce lysis. D. They induce mucus production that helps flush the toxin or virus out of the body. E. They bind to epithelial cells and induce the production of antimicrobial peptides.
A. Most vaccines against virus infections or bacterial toxins function by eliciting neutralizing antibodies. These antibodies bind to the virus or toxin immediately after entry (for the virus) or production by the bacteria (for the toxin) and prevent them from binding to and entering our cells.
The majority of vaccines work by eliciting pathogen-specific antibodies that circulate in our bodies and protect us in the event that we are later exposed to that specific pathogen. For most viruses and bacterial toxins that we are vaccinated against, these pre-existing antibodies are protective because: A. They neutralize the virus or toxin, preventing it from attaching to and entering our cells. B. They bind to the virus or toxin and carry it to the liver where it can be degraded. C. They bind to the virus or toxin and directly induce lysis. D. They induce mucus production that helps flush the toxin or virus out of the body. E. They bind to epithelial cells and induce the production of antimicrobial peptides.
A. Most vaccines against virus infections or bacterial toxins function by eliciting neutralizing antibodies. These antibodies bind to the virus or toxin immediately after entry (for the virus) or production by the bacteria (for the toxin) and prevent them from binding to and entering our cells.
The importance of complement activation as an innate immune defense against infections is illustrated by: A. The evolution of complement avoidance strategies by many pathogens B. The large number of proteins involved in the complement pathway C. The large number of complement regulatory pathways expressed by the host D. The existence of three different mechanisms for initiating complement activation E. The ability of the membrane attack complex to lyse some pathogens
A. One of the best indicators of the importance of an immune protective mechanism is the development by pathogens of strategies to evade that mechanism. In the case of the complement pathway, many pathogens have evolved strategies to avoid complement activation on their surface. These include the expression of proteins that attract complement regulatory proteins to their surface, in an effort to mimic host cell surfaces that can inactivate complement. An additional strategy is to secrete proteins that directly inhibit components of the complement pathway.
B cells express a complement receptor that binds to C3b cleavage products, such as iC3b and C3dg. When a B cell with an antigen receptor that specifically recognizes that pathogen also has its complement receptor stimulated because the pathogen is opsonized with these C3 fragments, B cell activation is greatly enhanced. Due to this mechanism, B cells can be activated by much lower concentrations of antigen (in this case, the pathogen) than if the antigen is devoid of complement components. This mechanism functions to: A. Ensure that pathogens are readily detected by the adaptive immune system before they replicate to high levels in the host B. Prevent B cells from being activated in response to antigens that are not pathogens C. Allow B cells to phagocytose the pathogen and help destroy it D. Induce increased rounds of B cell replication to make more pathogen-specific B cells E. Allow the B cell to block pathogen replication by interfering with multiple pathogen surface functions
A. The complement receptor on B cells, CD21, is often referred to as the B cell co-receptor. When this receptor is engaged together with the B cell antigen receptor, the B cell can be activated by much lower concentrations of antigen compared to antigen lacking ligands for CD21. Experiments have indicated that CD21 stimulation can reduce the concentration of antigen needed to activate the B cell by 100-1000-fold. This allows B cells to detect small numbers of infecting pathogens, to initiate an adaptive response prior to the occurrence of a high pathogen load in the host.
1.10 Multiple choice: When macrophages in a tissue encounter bacteria, they release cytokines that induce an inflammatory response. These cytokines act on other immune cells, to recruit them to the site of infection and to enhance their activities. In addition, these cytokines act on the endothelial cells of the blood vessel wall to: A. Increase their permeability, allowing fluid and proteins to leak into the tissue B. Solidify the tight junctions to prevent the bacteria from entering the blood C. Proliferate, allowing the blood vessel to enlarge D. Up-regulate microbicidal mechanisms, so they can kill bacteria E. Secrete anti-microbial peptides
A. The inflammatory response induced by macrophage-derived cytokines leads to the recruitment of cells, fluid, and soluble mediators into the tissue at the site of an infection. A key aspect of this response is the action of inflammatory cytokines on the blood vessel endothelial cells. These cells up-regulate adhesion molecules, allowing circulating white blood cells to stick to the blood vessel wall near the site of infection. In addition, the junctions between the endothelial cells loosen, allowing fluid and cells to leak out of the vessel into the tissue. In the fluid are soluble mediators, such as antimicrobial peptides, complement proteins, and antibodies.
When macrophages in a tissue encounter bacteria, they release cytokines that induce an inflammatory response. These cytokines act on other immune cells, to recruit them to the site of infection and to enhance their activities. In addition, these cytokines act on the endothelial cells of the blood vessel wall to: A. Increase their permeability, allowing fluid and proteins to leak into the tissue B. Solidify the tight junctions to prevent the bacteria from entering the blood C. Proliferate, allowing the blood vessel to enlarge D. Up-regulate microbicidal mechanisms, so they can kill bacteria E. Secrete anti-microbial peptides
A. The inflammatory response induced by macrophage-derived cytokines leads to the recruitment of cells, fluid, and soluble mediators into the tissue at the site of an infection. A key aspect of this response is the action of inflammatory cytokines on the blood vessel endothelial cells. These cells up-regulate adhesion molecules, allowing circulating white blood cells to stick to the blood vessel wall near the site of infection. In addition, the junctions between the endothelial cells loosen, allowing fluid and cells to leak out of the vessel into the tissue. In the fluid are soluble mediators, such as antimicrobial peptides, complement proteins, and antibodies.
1.40 Multiple choice: One surprising aspect of the immune system is that individuals make responses to human tissues from a different individual, causing serious problems for organ and tissue transplantation. The basis for this immune response is: A. The extensive polymorphism of MHC genes in the human population B. The fact that transplanted tissues often carry infectious microbes into the recipient C. The fact that individuals may differ in their blood group antigens (i.e., their blood type) D. The presence of many antigen-presenting-cells in the transplanted tissue E. The presence of many B and T lymphocytes in the transplanted tissue
A. The major component of the graft rejection response is due to recognition of the 'foreign' MHC proteins on the graft by the recipient's T lymphocytes. This occurs because of the extensive polymorphism of MHC genes in the human population. As a result, two different individuals nearly always express different MHC molecules from each other. Since MHC molecules are efficiently recognized by T cells, the T cells in the recipient will respond to the donor's tissue and destroy it, just as if it were a pathogen.
1.21 Multiple choice: The pattern recognition receptors on cells of the innate immune system are genetically encoded, meaning that their sequences and specificities are determined prior to the development of the individual. In contrast, the antigen receptors of B and T lymphocytes arise from a random rearrangement process that occurs differently in each lymphocyte as it develops. One potential problem entailed by the random process that generates lymphocyte antigen receptors is the possibility that: A. Some antigen receptors might recognize the individuals on cells or antigens B. Many lymphocytes might generate antigen receptors that don't recognize anything C. Many lymphocytes might generate antigen receptors that recognize multiple different pathogens D. Some antigen receptors might recognize foreign tissues and lead to graft rejection during organ transplantation E. Some lymphocytes might not generate functional antigen receptor proteins
A. The random process that generates lymphocyte antigen receptors can create antigen receptors that are self-reactive. Many of these potentially self-reactive lymphocytes are eliminated during lymphocyte development, a process known as clonal deletion. Other self-reactive lymphocytes are functionally inactivated or inhibited from responding to their self-antigen. Altogether, these mechanisms ensure that the individual's lymphocytes remain tolerant to self.
The pattern recognition receptors on cells of the innate immune system are genetically encoded, meaning that their sequences and specificities are determined prior to the development of the individual. In contrast, the antigen receptors of B and T lymphocytes arise from a random rearrangement process that occurs differently in each lymphocyte as it develops. One potential problem entailed by the random process that generates lymphocyte antigen receptors is the possibility that: A. Some antigen receptors might recognize the individuals on cells or antigens B. Many lymphocytes might generate antigen receptors that don't recognize anything C. Many lymphocytes might generate antigen receptors that recognize multiple different pathogens D. Some antigen receptors might recognize foreign tissues and lead to graft rejection during organ transplantation E. Some lymphocytes might not generate functional antigen receptor proteins
A. The random process that generates lymphocyte antigen receptors can create antigen receptors that are self-reactive. Many of these potentially self-reactive lymphocytes are eliminated during lymphocyte development, a process known as clonal deletion. Other self-reactive lymphocytes are functionally inactivated or inhibited from responding to their self-antigen. Altogether, these mechanisms ensure that the individual's lymphocytes remain tolerant to self.
1.22 Multiple choice: Secondary (or peripheral) lymphoid organs are sites for initiation of adaptive immune responses. Given the rarity of lymphocytes specific for any given antigen and the vast amount of body tissue that must be protected, the system of secondary lymphoid tissues is efficient because: A. It concentrates antigens in centralized locations for rare lymphocytes to encounter B. It provides the optimal environment for the rapid proliferation of lymphocytes C. It traps the pathogens and antigens in a contained environment so they cannot spread to other tissues in the body D. It helps the innate immune cells eliminate the infection by using lymphatic fluid to drain pathogens from the infected tissue E. It filters the lymph fluid and removes pathogenic organisms before they can enter the bloodstream
A. The system of secondary lymphoid organs is important in promoting interactions between rare antigen-specific lymphocytes and their antigens. Instead of requiring each naive lymphocyte to traffic into every nook and cranny of the body, the pathogens and their products are brought to centralized locations and concentrated there. This allows the naive T and B lymphocytes to spend their time traveling from lymph node to lymph node looking for their antigen, making the encounters between lymphocytes and antigens much more efficient.
Secondary (or peripheral) lymphoid organs are sites for initiation of adaptive immune responses. Given the rarity of lymphocytes specific for any given antigen and the vast amount of body tissue that must be protected, the system of secondary lymphoid tissues is efficient because: A. It concentrates antigens in centralized locations for rare lymphocytes to encounter B. It provides the optimal environment for the rapid proliferation of lymphocytes C. It traps the pathogens and antigens in a contained environment so they cannot spread to other tissues in the body D. It helps the innate immune cells eliminate the infection by using lymphatic fluid to drain pathogens from the infected tissue E. It filters the lymph fluid and removes pathogenic organisms before they can enter the bloodstream
A. The system of secondary lymphoid organs is important in promoting interactions between rare antigen-specific lymphocytes and their antigens. Instead of requiring each naive lymphocyte to traffic into every nook and cranny of the body, the pathogens and their products are brought to centralized locations and concentrated there. This allows the naive T and B lymphocytes to spend their time traveling from lymph node to lymph node looking for their antigen, making the encounters between lymphocytes and antigens much more efficient.
Although the complement cascade can be initiated by antibodies bound to the surface of a pathogen, complement activation is generally considered to be an innate immune response. This is because: A. Two of the three pathways for complement activation are initiated by constitutively produced recognition molecules that directly interact with microbial surfaces. B. When the complement cascade leads to the formation of a membrane-attack complex, the pathogen is killed. C. Several of the soluble products generated by complement activation lead promote the inflammatory response. D. Complement proteins bound to the pathogen promote uptake and destruction by phagocytic cells. E. The C3 convertase is only produced when complement activation is initiated by antibody binding to a pathogen.
A. There are three pathways for initiating complement activation. One of them, known as the classical pathway, occurs when the pathogen has antibodies bound to its surface, leading to recruitment of C1q. The other two pathways, the lectin pathway and the alternative pathway, are initiated by mechanisms that do not require antibodies directed against the pathogen surface. These latter two pathways are dependent on constitutively produced, and therefore 'innate' recognition molecules that directly bind to pathogen surfaces, initiating complement activation.
One surprising aspect of the immune system is that individuals make responses to human tissues from a different individual, causing serious problems for organ and tissue transplantation. The basis for this immune response is: A. The extensive polymorphism of MHC genes in the human population B. The fact that transplanted tissues often carry infectious microbes into the recipient C. The fact that individuals may differ in their blood group antigens (i.e., their blood type) D. The presence of many antigen-presenting-cells in the transplanted tissue E. The presence of many B and T lymphocytes in the transplanted tissue
A. Two different individuals nearly always express different MHC molecules from each other. Since MHC molecules are efficiently recognized by T cells, the T cells in the recipient will respond to the donor's tissue and destroy it, just as if it were a pathogen.
Adaptive immune responses are slow to develop, taking days to weeks after exposure to reach their peak. However, these responses are more specific than innate responses, and also generate immunological memory. These latter features, which provide enhanced protection upon re-infection with the same pathogen, are the basis of: A. Vaccines B. Antibiotics C. Systemic shock D. Complement activation E. Phagocytosis
A. Vaccines are designed to generate an adaptive immune response to a non-disease-causing form of a pathogen, or a pathogen product. Due to the specificity of this response, and the generation of immunological memory, vaccinated individuals make a substantially more robust response, and are often completely protected from infection, when exposed to the pathogen at a later time.
1.41 Multiple choice: Vaccination against many infectious diseases has provided enormous benefit in developed countries, leading to the virtual eradication of diseases such as polio, measles, smallpox, and others. However, efforts to create long-lasting vaccines against some viral infections, like Influenza and HIV, have not been successful to date because: A. Viruses like HIV and Influenza undergo antigenic variation to evade previous immune responses. B. Viruses like HIV and Influenza spread too rapidly in the population for a vaccine to be effective. C. Viruses like HIV and Influenza have RNA, rather than DNA genomes, and are resistant to current vaccine strategies. D. Viruses like HIV and Influenza infect via mucosal surfaces, a route that is not well protected by current vaccine strategies. E. Viruses like HIV and Influenza are transmitted vertically (from mother to child) during fetal development, so babies are infected before they can be vaccinated.
A. Viruses like HIV and influenza undergo rapid antigenic variation. Therefore, an immune response against one strain of the virus will not usually protect individuals from infection with a variant strain. Therefore, much of the current effort toward developing vaccines against these viruses aims at targeting highly conserved regions of the virus, where an immune response would be broadly reactive to many viral variants.
Vaccination against many infectious diseases has provided enormous benefit in developed countries, leading to the virtual eradication of diseases such as polio, measles, smallpox, and others. However, efforts to create long-lasting vaccines against some viral infections, like Influenza and HIV, have not been successful to date because: A. Viruses like HIV and Influenza undergo antigenic variation to evade previous immune responses. B. Viruses like HIV and Influenza spread too rapidly in the population for a vaccine to be effective. C. Viruses like HIV and Influenza have RNA, rather than DNA genomes, and are resistant to current vaccine strategies. D. Viruses like HIV and Influenza infect via mucosal surfaces, a route that is not well protected by current vaccine strategies. E. Viruses like HIV and Influenza are transmitted vertically (from mother to child) during fetal development, so babies are infected before they can be vaccinated.
A. Viruses like HIV and influenza undergo rapid antigenic variation. Therefore, an immune response against one strain of the virus will not usually protect individuals from infection with a variant strain. Therefore, much of the current effort toward developing vaccines against these viruses aims at targeting highly conserved regions of the virus, where an immune response would be broadly reactive to many viral variants.
Early studies analyzing the antibody protein fragments generated after proteolytic cleavage revealed important information about the overall structure of the antibody molecule. Which cleavage pattern (indicated by the red triangles in Figure Q4.5) yields a fragment that has the same antigen-binding avidity as the intact antibody, but is unable to activate complement after binding to a pathogen?
A. (six red attachments)
Multiple choice: The adaptive immune system developed a strategy for monitoring the proteins synthesized in virtually any cell in the body, thereby preventing pathogens from 'hiding out' by adopting an intracellular lifestyle. To accomplish this, the immune system: A. Co-opted the ubiquitin-proteasome system used by cell for protein turnover B. Created a novel pathway using the immunoproteasome for generating peptides C. Created a novel pathway to express foreign proteins on the cell surface D. Took advantage of proteolytic enzymes present in endocytic vesicles E. Engineered an immune-specific ubiquitin molecule for tagging foreign proteins
A. Co-opted the ubiquitin-proteasome system used by cell for protein turnover
B cells express a complement receptor that binds to C3b cleavage products, such as iC3b and C3dg. When a B cell with an antigen receptor that specifically recognizes that pathogen also has its complement receptor stimulated because the pathogen is opsonized with these C3 fragments, B cell activation is greatly enhanced. Due to this mechanism, B cells can be activated by much lower concentrations of antigen (in this case, the pathogen) than if the antigen is devoid of complement components. This mechanism functions to: A. Ensure that pathogens are readily detected by the adaptive immune system before they replicate to high levels in the host B. Prevent B cells from being activated in response to antigens that are not pathogens C. Allow B cells to phagocytose the pathogen and help destroy it D. Induce increased rounds of B cell replication to make more pathogen-specific B cells E. Allow the B cell to block pathogen replication by interfering with multiple pathogen surface functions
A. Ensure that pathogens are readily detected by the adaptive immune system before they replicate to high levels in the host
Multiple choice: B cells express a complement receptor that binds to C3b cleavage products, such as iC3b and C3dg. When a B cell with an antigen receptor that specifically recognizes that pathogen also has its complement receptor stimulated because the pathogen is opsonized with these C3 fragments, B cell activation is greatly enhanced. Due to this mechanism, B cells can be activated by much lower concentrations of antigen (in this case, the pathogen) than if the antigen is devoid of complement components. This mechanism functions to: A. Ensure that pathogens are readily detected by the adaptive immune system before they replicate to high levels in the host B. Prevent B cells from being activated in response to antigens that are not pathogens C. Allow B cells to phagocytose the pathogen and help destroy it D. Induce increased rounds of B cell replication to make more pathogen-specific B cells E. Allow the B cell to block pathogen replication by interfering with multiple pathogen surface functions
A. Ensure that pathogens are readily detected by the adaptive immune system before they replicate to high levels in the host
The TCR signaling module leading to transcription factor activation is dependent on the enzyme phospholipase-C-y (PLC-y). The mechanism by which PLC-y activates multiple transcription factors is by: A. Generating two small second messengers that act on multiple target proteins in the T cell B. Directly cleaving inhibitory subunits of multiple transcription factors, thereby releasing the active transcription factors C. Generating two small second messengers that diffuse to the nucleus and activate transcription factors present there D. Generating two small second messengers that act as chaperones to promote nuclear localization of transcription factors E. Directly cleaving the lipid binding domain from membrane-tethered transcription factors, allowing them to migrate to the nucleus
A. Generating two small second messengers that act on multiple target proteins in the T cell
Multiple choice: Several types of pathogens encode proteins that function as superantigens, which activate massive numbers of T cells in an individual. One example is the staphylococcal enterotoxins that cause food poisoning. These superantigens are the exception to the general rule that T cells only recognize specific peptide:MHC complexes, because they: A. Induce activation of any T cell whose T-cell receptor uses a particular Vβ region bound by that superantigen B. Simultaneously stimulate all of the T-cell receptors on a given T cell C. Cover up the peptide-binding site, preventing MHC molecules from binding peptides D. Activate a large number of T cells that are specifically recognizing peptides derived from the superantigen protein E. Induce anti-microbial cytokine production that aids the immune system in clearing the pathogen
A. Induce activation of any T cell whose T-cell receptor uses a particular Vβ region bound by that superantigen
Multiple choice: Chemokines such as CXCL8 have a key role in the rapid recruitment of neutrophils to the site in the tissue containing the focus of an infection. In this response, CXCL8 has two different functions. In addition to inducing integrin activation on the neutrophil, CXCL8 also functions to: A. Induce directional migration of the neutrophil in the tissue B. Induce increased expression of P-selectin and E-selectin on the endothelium C. Induce increased expression of integrins on the neutrophil surface D. Induce blood vessel dilation and fluid leakage into the infected tissue E. Induce increased phagocytic activity by the neutrophil
A. Induce directional migration of the neutrophil in the tissue
1.42 Synthesis question: For each of the panels A-D in Figure Q1.42, identify the most likely component(s) of the immune response indicated by the red arrow, and briefly describe your reasoning. PICTURE ON LAPTOP
A. Innate immune response. The cells responding could be mast cells, dendritic cells, macrophages, or ILCs. The response initiates rapidly (<1 day) and lasts for 2-3 days, then disappears. B. Primary adaptive immune response. Upon first exposure to antigen or pathogen, the response of B cells or T cells takes approximately 1 week to arise. It lasts for two weeks or so, then wanes. C. Memory response of adaptive immune cells. Upon secondary exposure to the same antigen or pathogen, the response of B or T lymphocytes is more rapid than the primary response, and generates a response of greater magnitude than the primary response. D. Primary adaptive immune response to a different antigen. Each time the immune system encounters an antigen/pathogen for the first time, a primary response is generated. This response will look similar each time. It is only when the same antigen/pathogen is encountered for a second time that a more rapid and more robust adaptive immune response is generated.
Multiple choice: Secondary (or peripheral) lymphoid organs are sites for initiation of adaptive immune responses. Given the rarity of lymphocytes specific for any given antigen and the vast amount of body tissue that must be protected, the system of secondary lymphoid tissues is efficient because: A. It concentrates antigens in centralized locations for rare lymphocytes to encounter B. It provides the optimal environment for the rapid proliferation of lymphocytes C. It traps the pathogens and antigens in a contained environment so they cannot spread to other tissues in the body D. It helps the innate immune cells eliminate the infection by using lymphatic fluid to drain pathogens from the infected tissue E. It filters the lymph fluid and removes pathogenic organisms before they can enter the bloodstream
A. It concentrates antigens in centralized locations for rare lymphocytes to encounter
Secondary (or peripheral) lymphoid organs are sites for initiation of adaptive immune responses. Given the rarity of lymphocytes specific for any given antigen and the vast amount of body tissue that must be protected, the system of secondary lymphoid tissues is efficient because: A. It concentrates antigens in centralized locations for rare lymphocytes to encounter B. It provides the optimal environment for the rapid proliferation of lymphocytes C. It traps the pathogens and antigens in a contained environment so they cannot spread to other tissues in the body D. It helps the innate immune cells eliminate the infection by using lymphatic fluid to drain pathogens from the infected tissue E. It filters the lymph fluid and removes pathogenic organisms before they can enter the bloodstream
A. It concentrates antigens in centralized locations for rare lymphocytes to encounter
Multiple choice: When stimulated by binding to bacterial products, the fMet-Leu-Phe (fMLF) receptor triggers multiple responses by phagocytes, including migration and induction of antimicrobial activities. Most of these responses are activated by small GTPases of the Rac and Rho families that are indirectly activated by fMLF receptor stimulation. The fMLF receptor can initiate multiple downstream signaling pathways because: A. It couples to a heterotrimeric G protein that has alpha and beta-gamma subunits with independent activities. B. It couples directly to two different guanine nucleotide exchange factors (GEFs). C. It binds to Rac, Rho, and cdc42 directly. D. It promotes fusion of phagosomes with lysosomes, initiating multiple signals. E. It induces assembly of multiple enzymes from individual cytosolic components.
A. It couples to a heterotrimeric G protein that has alpha and beta-gamma subunits with independent activities.
Multiple choice: Once expressed on the surface of host cells, an MHC protein remains stably associated with its bound peptide for several days. This highly stable peptide binding behavior is important because: A. It prevents peptide exchanges on the cell surface, ensuring that peptide:MHC complexes are reliable indicators of the proteins present inside that host cell. B. If the MHC protein lost its peptide it would become unstable, and would be rapidly internalized and degraded. C. Pathogens would otherwise evade the immune response by making decoy peptides that mimic host cell peptides. D. Pathogens would be able to evade the T cell response by making proteases that cleave MHC proteins inducing peptide release. E. Immune responses to infection often induce noxious chemicals that damage surface MHC proteins, and might result in peptide loss.
A. It prevents peptide exchanges on the cell surface, ensuring that peptide:MHC
Once expressed on the surface of host cells, an MHC protein remains stably associated with its bound peptide for several days. This highly stable peptide binding behavior is important because: A. It prevents peptide exchanges on the cell surface, ensuring that peptide:MHC complexes are reliable indicators of the proteins present inside that host cell. B. If the MHC protein lost its peptide it would become unstable, and would be rapidly internalized and degraded. C. Pathogens would otherwise evade the immune response by making decoy peptides that mimic host cell peptides. D. Pathogens would be able to evade the T cell response by making proteases that cleave MHC proteins inducing peptide release. E. Immune responses to infection often induce noxious chemicals that damage surface MHC proteins, and might result in peptide loss.
A. It prevents peptide exchanges on the cell surface, ensuring that peptide:MHC complexes are reliable indicators of the proteins present inside that host cell
TNF-receptor signaling commonly includes several steps that are regulated by ubiquitination. One important step following TNF-receptor stimulation is the: A. K48-linked ubiquitination and degradation of a TRAF protein, itself a ubiquitin-ligase B. K48-linked ubiquitination of the TNF-receptor cytoplasmic tail, leading to its degradation C. K63-linked ubiquitination of the TNF-receptor, providing a docking site for TRAF protein binding D. K48-linked ubiquitination of NIK, the NFkB-inducing kinase E. K63-linked ubiquitination of cIAP, leading to its binding to NIK, the NFkB-inducing kinase
A. K48-linked ubiquitination and degradation of a TRAF protein, itself a ubiquitin-ligase
The immunosuppressive drug rapamycin acts by inhibiting mTOR. When activated T cells are treated with rapamycin in a cell culture assay, they show greatly diminished proliferation, and accumulate to much lower numbers than control-treated cells. This is because: A. Rapamycin inhibits cells from increasing their synthesis of lipids and proteins. B. Rapamycin inhibits cells from activating the pro-survival protein, Bcl-2. C. Rapamycin inhibits DNA synthesis in activated T cells. D. Rapamycin inhibits cell cycle progression in activated T cells. E. Rapamycin inhibits the T cell's production of the growth factor, IL-2.
A. Rapamycin inhibits cells from increasing their synthesis of lipids and proteins
Multiple choice: Early studies analyzing the antibody protein fragments generated after proteolytic cleavage revealed important information about the overall structure of the antibody molecule. Which cleavage pattern (indicated by the red triangles in Figure Q4.5) yields a fragment that has the same antigen-binding avidity as the intact antibody, but is unable to activate complement after binding to a pathogen? (SEE IMAGE)
A. SEE IMAGE
Multiple choice: In Figure Q4.8, which close-up view of these two V domains has the amino acid sequences most important for antigen-binding highlighted correctly in red? (SEE IMAGE)
A. SEE IMAGE
The pattern recognition receptors on cells of the innate immune system are genetically encoded, meaning that their sequences and specificities are determined prior to the development of the individual. In contrast, the antigen receptors of B and T lymphocytes arise from a random rearrangement process that occurs differently in each lymphocyte as it develops. One potential problem entailed by the random process that generates lymphocyte antigen receptors is the possibility that: A. Some antigen receptors might recognize the individuals on cells or antigens B. Many lymphocytes might generate antigen receptors that don't recognize anything C. Many lymphocytes might generate antigen receptors that recognize multiple different pathogens D. Some antigen receptors might recognize foreign tissues and lead to graft rejection during organ transplantation E. Some lymphocytes might not generate functional antigen receptor proteins
A. Some antigen receptors might recognize the individuals on cells or antigens
Multiple choice: The pattern recognition receptors on cells of the innate immune system are genetically encoded, meaning that their sequences and specificities are determined prior to the development of the individual. In contrast, the antigen receptors of B and T lymphocytes arise from a random rearrangement process that occurs differently in each lymphocyte as it develops. One potential problem entailed by the random process that generates lymphocyte antigen receptors is the possibility that: A. Some antigen receptors might recognize the individuals own cells or antigens B. Many lymphocytes might generate antigen receptors that don't recognize anything C. Many lymphocytes might generate antigen receptors that recognize multiple different pathogens D. Some antigen receptors might recognize foreign tissues and lead to graft rejection during organ transplantation E. Some lymphocytes might not generate functional antigen receptor proteins
A. Some antigen receptors might recognize the individuals own cells or antigens
Multiple choice: Septic shock is a serious, often fatal response to an infection in the bloodstream. This response can be elicited in mice by intravenous injection of bacterial LPS. However, it was found that one strain of mice, C3H/HeJ, is resistant to LPS- induced shock. This fact was used to clone the gene for TLR-4 based on positional cloning from C3H/HeJ mice. Another example of a strain of mice that is resistant to LPS- induced septic shock is: A. TNF-receptor-deficient mice B. TLR-2-deficient mice. C. LFA-1-deficient mice D. Neutrophil-deficient mice E. Complement receptor-deficient mice
A. TNF-receptor-deficient mice
Multiple choice: Signaling through the Drosophila Toll pathway is initiated when pathogen recognition receptors (PRRs) bind to microbial products, such as bacterial peptidoglycan. Aspects of this pathway share similarity to the mammalian complement cascade as well as to the innate recognition system based on TLRs. One feature of Toll signaling that resembles the complement pathway is: A. The activation of an extracellular proteolytic cascade involving cleavage of self-proteins B. The deposition of Toll signaling proteins onto the microbial surface C. The release of soluble fragments of Toll that induce inflammation D. The assembly of a membrane attack complex in the microbial membrane following Toll activation E. The presence of receptors for Toll cleavage products on phagocytic cells to promote pathogen ingestion
A. The activation of an extracellular proteolytic cascade involving cleavage of self-proteins
Multiple choice: Stimulation of the nucleic acid sensing TLRs that reside in endosomal membranes induces the production of a different cytokine response than is produced by stimulation of the plasma membrane TLRs. In part, this distinction is based on the different adapter proteins used by the nucleic acid sensing TLRs, leading to the activation of IRF factors. The cytokine response following stimulation of nucleic acid-sensing TLRs is characterized by production of: A. The antiviral cytokine, type I interferon B. TNF-, which induces increased vascular permeability C. Antimicrobial peptides by macrophages D. Chemokines that recruit neutrophils E. The inflammatory complement fragments, C3a and C5a
A. The antiviral cytokine, type I interferon
Multiple choice: Stimulation of the nucleic acid sensing TLRs that reside in endosomal membranes induces the production of a different cytokine response than is produced by stimulation of the plasma membrane TLRs. In part, this distinction is based on the different adapter proteins used by the nucleic acid sensing TLRs, leading to the activation of IRF factors. The cytokine response following stimulation of nucleic acid-sensing TLRs is characterized by production of: A. The antiviral cytokine, type I interferon B. TNF-alpha, which induces increased vascular permeability C. Antimicrobial peptides by macrophages D. Chemokines that recruit neutrophils E. The inflammatory complement fragments, C3a and C5a
A. The antiviral cytokine, type I interferon
Multiple choice: Classical MHC molecules function as peptide-binding receptors that present these peptides to alpha:beta T cells for recognition by alpha:beta T-cell receptors. MHC molecules can be detected as far back in evolution as sharks, the same time at which T- cell receptors can be identified. Examination of shark MHC proteins indicates that these molecules likely function identically to human MHC molecules. This conclusion is based on: A. The conservation of amino acid residues important in peptide binding in both shark and human MHC proteins B. The observation that MHC genes are highly polymorphic in sharks as well as humans C. The fact that sharks have both MHC class I and MHC class II molecules D. The finding that sharks have both classical and nonclassical MHC molecules, like humans E. The ability to trace the evolution of MHC protein sequences from the earliest vertebrates to humans
A. The conservation of amino acid residues important in peptide binding in both shark and human MHC proteins
Multiple choice: Antibody diversity is generated by multiple mechanisms, each of which contributes to the generation of antibodies with up to 1011 different amino acid sequences in their antigen-binding sites. Several of these mechanisms involve changes in the DNA sequences encoding the antibody heavy and light chain proteins. One mechanism that does not rely on changes to the DNA within the immunoglobulin heavy and light chain gene loci is, instead, dependent on: A. The contributions of amino acids from both the heavy chain and the light chain to form the antigen-binding site B. The random usage of V, D, and J gene segments to form the heavy chain V region sequence C. The random usage of light chains versus light chains to pair with the heavy chain D. The activity of TdT to add random nucleotides at the junctions between the V, J, and D region sequences E. The fact that heavy chain V regions contain an extra gene segment encoded by the D region compared to light chain V regions
A. The contributions of amino acids from both the heavy chain and the light chain to form the antigen-binding site
Multiple choice: The importance of complement activation as an innate immune defense against infections is illustrated by: A. The evolution of complement avoidance strategies by many pathogens B. The large number of proteins involved in the complement pathway C. The large number of complement regulatory pathways expressed by the host D. The existence of three different mechanisms for initiating complement activation E. The ability of the membrane attack complex to lyse some pathogens
A. The evolution of complement avoidance strategies by many pathogens
The importance of complement activation as an innate immune defense against infections is illustrated by: A. The evolution of complement avoidance strategies by many pathogens B. The large number of proteins involved in the complement pathway C. The large number of complement regulatory pathways expressed by the host D. The existence of three different mechanisms for initiating complement activation E. The ability of the membrane attack complex to lyse some pathogens
A. The evolution of complement avoidance strategies by many pathogens.
One surprising aspect of the immune system is that individuals make responses to human tissues from a different individual, causing serious problems for organ and tissue transplantation. The basis for this immune response is: A. The extensive polymorphism of MHC genes in the human population B. The fact that transplanted tissues often carry infectious microbes into the recipient C. The fact that individuals may differ in their blood group antigens (i.e., their blood type) D. The presence of many antigen-presenting-cells in the transplanted tissue E. The presence of many B and T lymphocytes in the transplanted tissue
A. The extensive polymorphism of MHC genes in the human population
Multiple choice: Some T cells express gamma:delta T-cell receptors rather than alpha:beta T-cell receptors. The organization of the alpha locus and the delta locus helps to ensure that each T cell cannot express both types of T-cell receptors. The mechanism involved is that: A. The rearrangement of a T-cell receptor alpha gene deletes the delta locus on that allele. B. The rearrangement of a T-cell receptor delta gene deletes the alpha locus on that allele. C. The RAG recombinase enzymes are down-regulated immediately after the first T-cell receptor genes rearrange. D. The alpha:beta T-cell receptor signals the T cell to delete the delta locus. E. The gamma:delta T-cell receptor signals the T cell to delete the alpha locus.
A. The rearrangement of a T-cell receptor alpha gene deletes the delta locus on that allele.
Multiple choice: The majority of vaccines work by eliciting pathogen-specific antibodies that circulate in our bodies and protect us in the event that we are later exposed to that specific pathogen. For most viruses and bacterial toxins that we are vaccinated against, these pre-existing antibodies are protective because: A. They neutralize the virus or toxin, preventing it from attaching to and entering our cells. B. They bind to the virus or toxin and carry it to the liver where it can be degraded. C. They bind to the virus or toxin and directly induce lysis. D. They induce mucus production that helps flush the toxin or virus out of the body. E. They bind to epithelial cells and induce the production of antimicrobial peptides.
A. They neutralize the virus or toxin, preventing it from attaching to and entering our cells.
The majority of vaccines work by eliciting pathogen-specific antibodies that circulate in our bodies and protect us in the event that we are later exposed to that specific pathogen. For most viruses and bacterial toxins that we are vaccinated against, these pre-existing antibodies are protective because: A. They neutralize the virus or toxin, preventing it from attaching to and entering our cells. B. They bind to the virus or toxin and carry it to the liver where it can be degraded. C. They bind to the virus or toxin and directly induce lysis. D. They induce mucus production that helps flush the toxin or virus out of the body. E. They bind to epithelial cells and induce the production of antimicrobial peptides.
A. They neutralize the virus or toxin, preventing it from attaching to and entering our cells.
Multiple choice: Recombination signal sequences are conserved heptamer and nonamer sequences that flank the V, J, and D gene segments which undergo recombination to generate the final V region coding exon. Some of these have 12- nucleotide spacers between the heptamer and nonamer, and others have 23-nucleotide spacers. The reason recombination signal sequences come in these two forms is: A. To ensure the correct assembly of gene segments so that a VH recombines to a DH and not to another VH, for instance B. To ensure that the heptamer and nonamer are found on the same face of the DNA double helix C. To ensure that K, upside-down Y, and heavy chains recombine within a locus and not between loci D. To ensure that K, upside-down Y, and heavy chain gene segments do not undergo recombination with non-immunoglobulin genes E. To ensure that the RAG recombinase cuts the DNA between the last nucleotide of the heptamer and the coding sequence
A. To ensure the correct assembly of gene segments so that a VH recombines to a DH and not to another VH, for instance
Antibody binding to a pathogen surface is greatly enhanced when both antigen-binding sites of the antibody are engaged at once, a feature known as bivalent binding. It is possible for antibodies to bind bivalently to a wide variety of components on many different pathogen surfaces due to the flexibility in the protein at the hinge region and at the V-C junction. A. True B. False
A. True
For cells of the innate immune system, each individual cell has multiple pattern recognition receptors, and can recognize many different pathogens. In contrast, cells of the adaptive immune system each express only a single antigen receptor, and have a single specificity for pathogen recognition. A. True B. False
A. True
Innate lymphoid cells and NK cells are effector cells that respond rapidly after encountering a pathogen. Several different subsets of innate lymphoid cells exist, and each is specialized to respond to a category of pathogen (e.g., viruses, extracellular bacteria, helminthic parasites, etc). Innate lymphoid cells reside primarily in tissues such as the lungs, the lining of the gastrointestinal tract, and the skin, because these sites represent the major routes of entry of pathogens into the body A. True B. False
A. True
MHC class I molecules generally bind peptides that are 8-10 amino acids. Each allelic variant has preferences for the amino acid residues at key anchor positions, but will not bind every possible peptide containing the correct anchor residues. A. True B. False
A. True
Neutrophils regulate the production of active cathelicidins (a class of antimicrobial peptides) by segregating the inactive propeptide from the processing enzyme that cleaves and activates it in two different types of cytoplasmic granules. These two types of granules are induced to fuse with phagosomes after ingestion of microbes, bringing the processing enzyme and the propeptide together. A. True B. False
A. True
Phosphorylation of signaling proteins can have activating or inhibitory effects on protein function. In many cases, such as the activation of mTOR, the phosphorylation of an inhibitory protein leads to inactivation of the inhibitor, resulting in downstream signaling. A. True B. False
A. True
Several pathogens produce proteins, either membrane-bound or secreted, that inactivate C3b that might be deposited on the pathogen surface. C3b is specifically targeted due to its central position in all three complement pathways. A. True B. False
A. True
T cells expressing y:g TCRs are distinct from those expressing alpha:beta TCRs in that they do not generally recognize host cell responses to infections or tissue damage; rather they recognize components of the pathogen directly. A. True B. False
A. True
TH1, TH2, TH17, and T follicular helper (TFH) cells represent four different subsets of CD4 effector cells. Each of these subsets produces a distinct set of cytokines when stimulated, that in turn, act to mobilize distinct immune effector mechanisms. While TH1, TH2, and TH17 cells recruit and activate innate immune cells, TFH cells act to amplify the adaptive immune response. A. True B. False
A. True
The C3 convertase of the alternative complement pathway amplifies the overall magnitude of complement activation regardless of which of the three pathways initiated the complement activation initially. A. True B. False
A. True
The LAT:Gads:SLP-76 complex that assembles following TCR stimulation provides the scaffold for initiating multiple downstream signaling modules, leading to actin polymerization, integrin activation, and gene expression. A. True B. False
A. True
The spleen is a secondary lymphoid organ that performs several functions. In addition to its role as a site for initiating adaptive immune responses, the spleen is important in removing dead or damaged red blood cells from the circulation. Its immune function is important because blood-borne pathogens will not be transported to draining lymph nodes via the lymph fluid. A. True B. False
A. True
Although the complement cascade can be initiated by antibodies bound to the surface of a pathogen, complement activation is generally considered to be an innate immune response. This is because: A. Two of the three pathways for complement activation are initiated by constitutively produced recognition molecules that directly interact with microbial surfaces. B. When the complement cascade leads to the formation of a membrane-attack complex, the pathogen is killed. C. Several of the soluble products generated by complement activation lead promote the inflammatory response. D. Complement proteins bound to the pathogen promote uptake and destruction by phagocytic cells. E. The C3 convertase is only produced when complement activation is initiated by antibody binding to a pathogen.
A. Two of the three pathways for complement activation are initiated by constitutively produced recognition molecules that directly interact with microbial surfaces.
Multiple choice: Although the complement cascade can be initiated by antibodies bound to the surface of a pathogen, complement activation is generally considered to be an innate immune response. This is because: A. Two of the three pathways for complement activation are initiated by constitutively produced recognition molecules that directly interact with microbial surfaces. B. When the complement cascade leads to the formation of a membrane-attack complex, the pathogen is killed. C. Several of the soluble products generated by complement activation lead promote the inflammatory response. D. Complement proteins bound to the pathogen promote uptake and destruction by phagocytic cells. E. The C3 convertase is only produced when complement activation is initiated by antibody binding to a pathogen.
A. Two of the three pathways for complement activation are initiated by constitutively produced recognition molecules that directly interact with microbial surfaces.
Hepatitis C is a virus that infects hepatocytes, which are non-immune cells of the liver. Currently, patients with chronic Hepatitis C infections are treated with repeated administration of type I interferon, predominantly interferon . One aspect of this treatment that might aid the patient's immune system in clearing this virus infection is: A. Up-regulation of MHC class I expression levels on hepatocytes B. Activation of macrophages to produce noxious compounds that might kill the virus C. Induction of an inflammatory response to promote neutrophil trafficking to the liver D. Production of TNF- in response to type I interferon leading to vasodilation in the liver E. Induction of IL-1 and IL-6 leading to the acute phase response
A. Up-regulation of MHC class I expression levels on hepatocytes
Multiple choice: Hepatitis C is a virus that infects hepatocytes, which are non-immune cells of the liver. Currently, patients with chronic Hepatitis C infections are treated with repeated administration of type I interferon, predominantly interferon . One aspect of this treatment that might aid the patient's immune system in clearing this virus infection is: A. Up-regulation of MHC class I expression levels on hepatocytes B. Activation of macrophages to produce noxious compounds that might kill the virus C. Induction of an inflammatory response to promote neutrophil trafficking to the liver D. Production of TNF- in response to type I interferon leading to vasodilation in the liver E. Induction of IL-1 and IL-6 leading to the acute phase response
A. Up-regulation of MHC class I expression levels on hepatocytes
Vaccination against many infectious diseases has provided enormous benefit in developed countries, leading to the virtual eradication of diseases such as polio, measles, smallpox, and others. However, efforts to create long-lasting vaccines against some viral infections, like Influenza and HIV, have not been successful to date because: A. Viruses like HIV and Influenza undergo antigenic variation to evade previous immune responses. B. Viruses like HIV and Influenza spread too rapidly in the population for a vaccine to be effective. C. Viruses like HIV and Influenza have RNA, rather than DNA genomes, and are resistant to current vaccine strategies. D. Viruses like HIV and Influenza infect via mucosal surfaces, a route that is not well protected by current vaccine strategies. E. Viruses like HIV and Influenza are transmitted vertically (from mother to child) during fetal development, so babies are infected before they can be vaccinated.
A. Viruses like HIV and Influenza undergo antigenic variation to evade previous human responses.
Multiple choice: Vaccination against many infectious diseases has provided enormous benefit in developed countries, leading to the virtual eradication of diseases such as polio, measles, smallpox, and others. However, efforts to create long-lasting vaccines against some viral infections, like Influenza and HIV, have not been successful to date because: A. Viruses like HIV and Influenza undergo antigenic variation to evade previous immune responses. B. Viruses like HIV and Influenza spread too rapidly in the population for a vaccine to be effective. C. Viruses like HIV and Influenza have RNA, rather than DNA genomes, and are resistant to current vaccine strategies. D. Viruses like HIV and Influenza infect via mucosal surfaces, a route that is not well protected by current vaccine strategies. E. Viruses like HIV and Influenza are transmitted vertically (from mother to child) during fetal development, so babies are infected before they can be vaccinated.
A. Viruses like HIV and Influenza undergo antigenic variation to evade previous immune responses.
Multiple choice: Some CD1 molecules bind to glycosphingolipids, and are recognized by a subset of T cells known as invariant NKT (iNKT) cells. The ability of these T cells to recognize different glycolipid constituents from microorganisms when they are bound to CD1d places these cells in the 'innate immune' category. While iNKT cells do express a fully rearranged alpha:beta T-cell receptor, one key feature of the T-cell receptors expressed on iNKT cells also places them in the 'innate immune' category. This feature is: A. iNKT cells have a highly restricted T-cell receptor repertoire, with the majority of cells utilizing the same V-alpha and J-alpha rearrangement. B. iNKT cells express receptors that are also expressed on NK cells. C. iNKT cells express T-cell receptors that induce inhibitory, rather than activating signals. D. iNKT cells do not generally express CD4 or CD8. E. The T-cell receptors expressed on iNKT cells recognize both MHC class I and MHC class II molecules.
A. iNKT cells have a highly restricted T-cell receptor repertoire, with the majority of cells utilizing the same V-alpha and J-alpha rearrangement.
Defects in which of the following proteins do NOT result in severe combined immunodeficiency (SCID)?
AID
Defects in which of the following proteins does NOT result in severe combined immunodeficiency (SCID)?
AID
Which of the following do you expect would be actively functioning in a B cell that had migrated to a germinal center?
AID
Autoimmune polyendrocrinopathy-candidiasis-ectodermal dystrophy
AIRE
What is the main function of AIRE during lymphocyte development
AIRE is a transcription factor expressed by mTECs allowing them to express peptides from all over the body ensuring that the thymocytes that survive negative selection can tolerate self
Which of the following statements about NK-T cells is TRUE?
Activated NK-T cells can act as both TH and TC cells.
Strep throat is commonly caused by group A Streptococcus bacteria. A common symptom of strep throat is the presence of swollen lymph nodes in the neck. This symptom usually peaks about 2-4 days after the onset of the infection, and is due to:
Activation and proliferation of antigen-specific lymphocytes in the lymph nodes of the neck
Which of the following functions are macrophages unable to carry out?
Activation of naive T-cells
What of the following functions cannot be carried out by macrophages?
Activation of naïve T cells
Which of the following events occurs earliest in T-cell signaling?
Activation of protein tyrosine kinase Lck
Why does the adaptive immunity occur after the innate immune response?
Adaptive immunity occurs late, because the rare B cells and T cells specific for the invading pathogen must first undergo clonal expansion before they differentiate into effector cells that migrate to the site of infection and clear the infection.
Junctional diversity:
Additional diversity provided by TdT and nucleases
The binding of a monovalent Fab fragment to one binding site on an antigen
Affinity
When a mixture of different IgG antibody proteins are treated with the enzyme papain, each antibody is cleaved into three roughly equal size fragments. From each original antibody, two of the three fragments are identical to each other, and represent the 'arms' of the antibody 'Y'. These fragments are known as Fab fragments. The third fragment is known as the Fc region, because this fragment will crystallize when purified. The reason a mixture of Fc fragments will crystallize is because:
All Fc fragments generated from a mixture of IgG molecules have the identical amino acid sequence.
Cross-regulation of various members of a subset of T cells is frequently observed with:
All TH cells
What do all three pathways of complement activation have in common?
All generate C3 convertase (cleaves C3 into C3b and releases C3a)
Which of the following is used to generate diversity in the antibody repertoire?
All of the above: Presence of multiple variable gene segments that can be assembled in multiple different combinations Ability to pair a single heavy chain with different light chains, so as to avoid generation of autoreactive antibodies Addition of N nucleotides that are not encoded in the germ line Exonuclease trimming of excess nucleotides at variable segment junctions
How are antimicrobial peptides like defensin made?
All the antimicrobial peptides, including the defensins, are generated by proteolytic processing from inactive propeptides
Examples of pathogens that cause human disease include:
All: bacteria fungi parasites viruses
A(n) ____ is a molecule that is used by immune cells for communication.
All: chemoattractant chemokine interleukine cytokine
Malaria is caused by Plasmodium falciparum and Plasmodium vivax. These pathogens are transmitted when an individual is bitted by a Plasmodium-infected mosquito. This route of transmission:
Allows the parasite to avoid the normal mechanism blocking infections at barrier surfaces
Malaria is caused by Plasmodium falciparum and Plasmodium vivax. These pathogens are transmitted when an individual is bitten by a Plasmodium-infected mosquito. This route of transmission:
Allows the parasite to avoid the normal mechanisms blocking infections at barrier surfaces
Corticosteroids
Alteration of gene transcription profile
Which of the following accounts for the transition from IgM to IgD on a B cell surface?
Alternative splicing of pre-mRNA
Which of the following accounts for the transition from membrane-bound IgM to secreted IgM upon activation of a B-cell?
Alternative splicing of pre-mRNA
Most normal tissues contain resident macrophages, and connective tissue sites in the gastrointestinal tract and the lung contain large numbers of these cells. Yet the blood also contains a high number of circulating "classical" monocytes that can differentiate into macrophages after entering tissues. These circulating monocytes function to:
Amplify the local innate immune response by entering tissues that are infected
Most normal tissues contain resident macrophages, and connective tissue sites in the gastrointestinal tract and the lung contain large numbers of these cells. Yet the blood also contains a high number of circulating 'classical' monocytes that can differentiate into macrophages after entering tissues. These circulating monocytes function to:
Amplify the local innate immune response by entering tissues that are infected
Most normal tissues contain resident macrophages, and connective tissues sites in the gastrointestinal tract and the lung contain large numbers of these cells. Yet the blood also contains a high number of circulating 'classical' monocytes that can differentiate into macrophages after entering tissues. These circulating monocytes function to:
Amplify the local innate response by entering tissues that are infected
what is a PROTEASE?
An enzyme that breaks down proteins and peptides.
Which of the following statements is TRUE about an epitope?
An epitope is the area on an antigen that contacts antibody
Immunodeficiency diseases occur when individuals have defects in leukocyte adhesion to inflamed endothelial cells, thereby impeding the extravasation of phagocytes into infected tissues. When neutrophils from one class of these patients were isolated and tested using in vitro assays for neutrophil-endothelial cell interactions and extravasation, it was found that the neutrophils could slowly roll along the endothelial vessel wall but were unable to arrest and migrate across the endothelium. The most likely protein deficient in these neutrophils is:
An integrin
1. All blood cells in an adult human can trace their ancestry to which compartment within the body? A. Thymus B. Bone marrow C. Lymph node D. Peyer's patch E. None of the above,
Answer B
11. G proteins: A. bind GTP. B. dephosphrylate ITAMs. C. are transcription factors. D. downmodulate immune responses. E. are adhesion molecules
Answer: A
12. What is the central mechanism for establishing self-tolerance? A. Self-reactive T cells and B cells are killed during development. B. Individuals that have immune systems that respond to self-antigens do not survive to reproduce. C. Immune cells that react to self-antigens are turned off when they recognize self-tissues. D. Certain immune suppressive cytokines are maintained in tissues to dampen autoreactive immune responses. E. Peripheral tissues have mechanisms to kill T or B cells that respond to them.,
Answer: A
15. Antibodies consist of: A. two identical heavy chains and two identical light chains. B. an α chain, a β chain, a λ chain, and a κ chain. C. two α chains, an α chain, and a κ chain. D. two β chains, an α chain, and a κ chain. E. either an α chain or a β chain, a κ chain and a λ chain
Answer: A
2. A pluripotent stem cell can do which of the following? A. Differentiate into a finite number of different cell types B. Differentiate into any type of cell found in the adult C. Divide an infinite number of times D. All of the above E. None of the above,
Answer: A
21. Which of the following effector T lymphocyte populations is produced via the activation of a naïve T cell through antigen presented in MHC Class I? A. CTL B. TH1 C. TH2 D. TH17 E. None of the above
Answer: A
24. Regions of TCRs and BCRs that are particularly variable in their amino acid sequences are known for A. binding to antigen. B. sticking to denatured proteins. C. spanning the plasma membrane. D. binding to adaptor proteins. E. becoming phosphorylated.,
Answer: A
25. Conditions in which the immune system attacks self-antigens are known as: A. autoimmunity. B. immune deficiency. C. hypersensitivities. D. neuroplasias. E. None of the above,
Answer: A
3. Which of the following is the BEST example of herd immunity? A. A child infected with measles travels from Germany to the United States. Several babies contract the disease, but the outbreak is largely contained due to vaccinations. B. Certain populations of cattle are less susceptible to infection with encephalitis because of their genetic makeup. C. Once a certain threshold of individuals has been infected with a novel human pathogen, it is unlikely that any more will be. D. Geese and chickens are infected with different strains of influenza because they express different receptors on their cell surface. E. When infection spreads through a population, certain individuals generate stronger immune responses than others
Answer: A
30. Which of the following does NOT appear to utilize the FRCC system as its primary means for trafficking through the lymph node? A. B cells B. T cells C. Free antigen that entered via an afferent lymphatic D. Cytokines and chemokines E. None of the above utilizes the FRCC system
Answer: A
4. From which of the following stem cells are NK cells derived? A. CLP B. CMP C. CEP D. Both A and B E. None of the above,
Answer: A
4. Which of the following BEST describes how cytokines are released from activated T cells? A. Cytokines are released near where T-cell receptors are clustered. B. T cells release cytokines on the side of the cell opposite the MTOC in order to more efficiently distribute the response around the cell. C. T cells release cytokines evenly around the cell. D. Cytokines are released in short bursts from pre-formed vesicles full of cytokines. E. Cytokines are released in whatever direction the MTOC happens to be facing upon TCR ligation
Answer: A
5. Receptors that dimerize upon ligand binding often contain______________in their cytoplasmic domains. A. tyrosine kinases B. hydrophobic regions C. proteases D. metal-binding regions E. large immunoglobulin folds
Answer: A
8. From which of the following stem cells are helper T cells (TH) derived? A. CLP B. CMP C. CEP D. Both A and B E. None of the above,
Answer: A
1. Which is the best definition of "immunity"? A. The state of having been exposed to a pathogen repeatedly B. The state of being resistant to reinfection with a pathogen C. When an individual has never been exposed to a pathogen D. When the immune system is activated E. When physical barriers are not enough to prevent infection,
Answer: B
1. Which of the following types of bonds would be LEAST likely in a receptor-ligand interaction? A. Ionic bond B. Covalent bond C. Hydrogen bond D. Hydrophobic interaction E. Ionic bond
Answer: B
10. Which transcription factor becomes translocated to the nucleus downstream of calmodulin activation? A. NF-κB B. NFAT C. STAT1 D. STAT2 E. STAT3
Answer: B
11. What level of gene expression is regulated by such factors as Notch1, GATA-2 and Bmi-1? A. Replication B. Transcription C. RNA processing D. Translation E. None of the above,
Answer: B
17. An antibody's idiotype refers to: A. the kind of Fc region it contains. B. the sequence of its CDR. C. Ii's allelic form. D. whether it is membrane bound or secreted. E. which accessory molecules associate with it.,
Answer: B
22. Which of the following types of effector T lymphocytes is capable of inhibiting an immune response to an antigen recognized with its T-cell receptor (TCR)? A. TH1 B. Treg C. TH2 D. TH17 E. None of the above
Answer: B
22. Which of the following would be BEST for depleting an entire class of antibodies? A. Anti-idiotype antibody B. Anti-isotype antibodies C. Anti-CD19 D. Anti-CD4 E. Anti-CD8,
Answer: B
23. What occurs when someone receives a tissue transplant from an unrelated individual? A. The host's lymphocytes enter the tissues and become suppressed. B. The host's lymphocytes enter the tissues and become activated. C. The host's lymphocytes that react to the tissue graft are deleted in the thymus. D. The donor's lymphocytes suppress the host's lymphocytes, allowing for graft survival. E. The donor's lymphocytes destroy the host's immune system.,
Answer: B
23. Which of the following BEST describes why it is challenging for surface immunoglobulin to transduce a signal into the cell upon antigen binding? A. It takes twice as much antigen to stimulate the cells because each antibody has two antigen binding sites. B. The cytoplasmic domain of surface Ig only has three amino acids. C. Igα is rapidly dephosphorylated. D. Ig is an inflexible molecule. E. All of the above.,
Answer: B
6. Portions of the cytoplasmic domains of many immune receptors are targets for phosphorylation. These domains are known as: A. Grb domains. B. ITAMs. C. leucine zipper motifs. D. SOS domains. E. None of the above
Answer: B
7. From which of the following stem cells are eosinophils derived? A. CLP B. CMP C. CEP D. Both A and B E. None of the above,
Answer: B
7. Lipid rafts are highly ordered regions of the cell membrane that are enriched in: A. unsaturated fats. B. cholesterol. C. metabolic proteins. D. clathrin. E. tubulin
Answer: B
9. From which of the following stem cells are monocytes derived? A. CLP B. CMP C. CEP D. Both A and B E. None of the above,
Answer: B
9. Which of the following is the CORRECT relationship? A. PIP2 = PIP3 - DAG B. PIP2 = IP3 + DAG C. PLC = PIP2 + PIP3 D. DAG = PIP2 + PIP3 E. PIP3 = IP3 + PIP2
Answer: B
before exiting as single-positive, naïve T cells, they pass through a period in which they are double ________. A. positive-negative B. negative-positive C. Both of these are true. D. Neither of these are true. E. Coreceptor expression state does not change in the thymus
Answer: B
18. How do memory cells develop? A. Upon reinfection, memory centers in the brain send signals to the bone marrow to induce T-cell and B-cell differentiation. B. T cells and B cells from the primary response persist and become reactivated. C. Innate cells are trained to activate new T cells and B cells more quickly with secondary infection. D. T cells and B cells from the primary infection slowly mutate their receptors over time, priming themselves for the secondary response. E. Innate cells modify their cell surface receptors to prepare for reinfection
Answer: B 19. Which of the following is the BEST example of a hypersensitivity reaction? A. T cells responding vigorously to the flu virus B. B cells failing to respond to HIV allowing it to replicate out of control C. Inflammation of the airways in response to pollen D. Anemia as a result of iron deficiency E. T cells attacking the myelin sheath of nerves resulting in paralysis Answer: C
10. From which of the following stem cells are RBCs derived? A. CLP B. CMP C. CEP D. Both A and B E. None of the above,
Answer: C
11. Which of the following classes of cell surface receptors are directly encoded in the germline? A. TCR B. BCR C. PRR D. Antibodies E. All of the above
Answer: C
12. Which lineage of immune cells constitutes the first line of defense against an infection? A. Lymphoid B. Erythroid C. Myeloid D. All of the above E. None of the above
Answer: C
13. Immunoglobulin domains consist of: A. series of α helices bound together by hydrophobic interactions in their side chains. B. α helices alternating with parallel β-pleated sheets. C. anti-parallel β-pleated sheets folded and stabilized by hydrophobic interactions. D. compact, parallel β sheets forming a barrel structure. E. α helices held together by leucine repeats
Answer: C
14. Which of the following granulocytes contains histamine within its granules? A. Neutrophils B. Eosinophils C. Basophils D. Both B and C E. All of the above
Answer: C
2. Ka, the association constant, is a measure of which of the following? A. The concentration of unbound ligand B. The concentration of unbound receptor C. The affinity of receptor for ligand D. The size of the receptor relative to the ligand E. The number of ligands for each receptor
Answer: C
2. What happens to a pathogen as it becomes attenuated? A. It becomes more dangerous to the host. B. It gets smaller. C. It has weakened virulence. D. At becomes older. E. All of the above,
Answer: C
20. Which of the following cell types secretes IL-17 and may play a role in anti-fungal responses? A. TH1 B. TH2 C. TH17 D. TFH E. Plasma cell
Answer: C
21. HIV disease is a/an: A. autoimmune disease. B. hypersensitivity disease. C. immunodeficiency. D. genetic disorder. E. allergic reaction
Answer: C
22. Predict the outcome of being immunosuppressed as it relates to the development of cancer. A. Immunosuppressed individuals are at lower risk of cancer because cytokines produced by the immune system induce cancer. B. Immunosuppressed individuals are at lower risk of cancer because they are more likely to contract infectious diseases. C. Immunosuppressed individuals are at higher risk of cancer because the immune system recognizes and destroys cancerous cells. D. Immunosuppressed individuals are at higher risk of cancer because they bear a higher load of microbes that damage host tissues. E. None of the above
Answer: C
26. As thymocytes develop, they are classified on the basis of the state of their T-cell receptors and which of the following? A. Which class of MHC they express on their surface B. The state of the immunoglobulin heavy and light chains on their surface C. The presence of coreceptor proteins CD4 and CD8 on their surface D. The expression of the transcription factor, FoxP3 E. None of the above
Answer: C
27. The antigen specific component of the B-cell receptor is: A. ITAM. B. CD19. C. Igα/β. D. CD21. E. Lyn
Answer: C
29. Naïve lymphocytes enter secondary lymphoid tissues via which of the following structures? A. Afferent lymphatics B. Efferent lymphatics C. HEVs D. Marginal sinus E. None of the above
Answer: C
4. Which of the following diseases does NOT currently have an effective vaccine? A. Chicken pox B. Polio C. HIV D. Small pox E. Diptheria,
Answer: C
6. From which of the following stem cells are platelets derived? A. CLP B. CMP C. CEP D. Both A and B E. None of the above,
Answer: C
15. Which of the following is NOT true about monocytes? A. They comprise between 5-10% of circulating leukocytes. B. They have the ability to differentiate into macrophages or dendritic cells. C. They can be subdivided into inflammatory monocytes and patrolling monocytes. D. They can give rise to platelets. E. All of the above are true.
Answer: D
18. Carbohydrate chains attached to the CH2 domains of IgA, IgD, and IgG are believed to: A. allow for closer contact between partner chains. B. confer stability to the molecule resulting in a higher desaturation temperature. C. prevent protease degradation. D. provide space for complement protein binding. E. increase binding affinity for antigen
Answer: D
18. Which of the following cell types is responsible for activating B cells in germinal centers? A. TH1 B. TH2 C. TH17 D. TFH E. Plasma cell
Answer: D
21. Large amounts of monoclonal antibodies in the serum of an individual might be an indicator of: A. infection. B. T-cell deficiency. C. autoimmune disease. D. myeloma. E. stress
Answer: D
24. Which of the following is NOT considered primary lymphoid tissue? A. Draining lymph node B. Thymus C. Peyer's patch D. Choices A and C are not primary lymphoid tissue. E. None of the above is primary lymphoid tissue
Answer: D
25. In mammals, T-cell development occurs in the ____________, while B-cell development occurs predominantly in the ______________. A. thymus- bursa of Fabricius B. bone marrow-mesenteric lymph nodes C. bone marrow- thymus D. thymus- bone marrow E. None of the above
Answer: D
26. CD4 binds to: A. TCRα B. TCRβ C. MHC class I D. MHC class II E. CD8,
Answer: D
28. Contraction of which of the following types of muscles is responsible for propulsion of lymph through the lymphatic system? A. Cardiac B. Skeletal C. Smooth D. Both B and C E. None of the above
Answer: D
5. From which of the following stem cells are DCs derived? A. CLP B. CMP C. CEP D. Both A and B E. None of the above,
Answer: D
8. Which of the following are well established ways that tyrosine phosphorylation directly affects signaling pathways? A. Inducing kinase activity B. Recruiting enzymes through SH2 domains C. Opening calcium channels D. Both a and b E. Both b and c
Answer: D
9. Which of the following is a fungal pathogen? A. Vibrio cholerae B. Leishmania major C. Poliovirus D. Candida albicans E. Bordetella pertussis,
Answer: D
13. Which of the following is NOT descended from the common lymphoid progenitor? A. T cells B. NK cells C. B cells D. Eosinophils E. All of the above are descended from the common lymphoid progenitor
Answer: D .
12. Which of the following is responsible for IL-2 expression in T cells? A. NF-κB B. NFAT C. AP1 D. Both A and B E. All of the above,
Answer: E
14. On the gel below, which bands would you expect to bind antigen? A. A B. B C. C D. D E. A, B, and C,
Answer: E
20. Receptors that bind the constant regions of antibodies are known as: A. B-cell receptors. B. T-cell receptors. C. idiotype receptors. D. toll-like receptors. E. Fc receptors
Answer: E
24. Which of the following is TRUE? A. Vaccines cause autism. B. Vaccines cause obesity. C. Vaccines cause cancer. D. Vaccines cause diabetes. E. None of the above,
Answer: E
6. Which of the following cell types are lymphocytes? A. Macrophages B. Mast cells C. Neutrophils D. Erythrocytes E. T cells,
Answer: E
Effectors of the humoral immune system are known as: A. antibodies. B. immunoglobulin. C. complement. D. B cells. E. All of the above,
Answer: E
20. The hygiene hypothesis posits that there is a connection between environmental conditions and certain inappropriate immune responses. If you were a supporter of the hygiene hypothesis, what recommendations would you make to keep people healthier?
Answer: Expose children to more common antigens found in dirt and in the outdoors. Reduce use of antimicrobials.
17. True or False? The innate and adaptive immune responses largely work independently of one another
Answer: False
1. Innate Immunity Adaptive Immunity 2.Is mediated by what cells? 3. What do they recognize? 4. How are the receptors encoded? 5. Why can't they control all infections alone? 6. What do they do in response to antigen?
Answer: Innate Immunity Adaptive Immunity Is mediated by what cells? Macrophages, NK cells, neutrophils, mast cells eosinophils T cells and B cells What do they recognize? Pathogen patterns Specific epitopes How are the receptors encoded? Germline Rearranged gene segments Why can't they control all infections alone? Pathogens evolve escape mechanisms Takes too long to develop What do they do in response to antigen? Engulf and destroy, induce inflammation Produce antibodies, kill infected cells
14. What are the hallmarks of inflammation? Describe the physical characteristics of someone experiencing an inflammatory response.,
Answer: Redness, swelling, heat, pain. Someone experiencing inflammation might have localized swelling and redness or itching, or may be experiencing faintness due to a lowering of blood pressure if more severe.
8. Two main early theories were proposed to explain how antigen-specific antibodies develop: the instructional theory and the selective theory. How did the two differ? Which was ultimately shown to be CORRECT?,
Answer: The selective theory says that, when an antigen receptor binds with an antigen, the cell becomes activated (or the cell is selected to proliferate and secrete more copies of the receptor). The instructional theory says that the antigen receptor molds itself to the antigen. The selective theory was shown to be correct.
You isolate naïve T cells from your own blood and want to polarize them to the TH1 lineage. You can use any of the following reagents to do this. Which would you choose?
Anti-TCR antibody IL-12 Anti-CD28 antibody
Pathogens cause damage to tissues in direct and indirect mechanisms. Which of the following is NOT a direct mechanism of tissue damage?
Anti-host antibodies
Which of the two antibodies shown in Figure Q4.9 are most likely to have the same antigen-binding specificity? Explain your reasoning.
Antibodies C and D (the two with orange parts). They have identical heavy chains, but differ in constant region and V region framework amino acid sequences of the light chains. The two light chains share identical amino acid sequences in their CDR1, CD2, and CD3 loops so it's likely these two would bind to the same antigen. The other antibodies differ in CDR sequences and would be unlikely to bind the same antigen, regardless of sharing light chain C region and V region framework sequences.
The vaccine to Haemophilus influenzae type b is called a conjugate vaccine. It is composed of the tetanus toxoid protein conjugated to the capsular polysaccharide of the H. influenzae type b bacteria. When used to vaccinate infants, the antibody response generated by this vaccine would include:
Antibodies to the bacterial polysaccharide and the tetanus toxoid
In the 1970s, immunologists discovered the genetic mechanism allowing a population of B cells to produce an enormous diversity of different antibodies. At the time, this discovery shocked the field of biology, as it called into question the 'immutable' nature of DNA, which was known to be the genetic material transmitted from generation to generation during the propagation of the species. Briefly describe this startling mechanism.
Antibody diversity generates when each developing B cell undergoes DNA rearrangement. This involves combination of small gene segments encoded as separate elements in the genome to form a complete coding sequence. The DNA of the B cell is then irrevocably altered and can't transmit all genetic information to the next generation.
In the 1970s, immunologists discovered the genetic mechanism allowing a population of B cells to produce an enormous diversity of different antibodies. At the time, this discovery shocked the field of biology, as it called into question the 'immutable' nature of DNA, which was known to be the genetic material transmitted from generation to generation during the propagation of the species. Briefly describe this startling mechanism.
Antibody diversity is generated when each developing B cell undergoes a DNA rearrangement process (to differentiate into plasma cells). This process involves the combination of small gene segments, encoded as separate elements in the genome, to form a complete coding sequence for the antibody protein. As a result of this process, the DNA of the B cell is irrevocably altered, and would no longer be able to transmit all the genetic information to the next generation.
1.18 Short answer: In the 1970s, immunologists discovered the genetic mechanism allowing a population of B cells to produce an enormous diversity of different antibodies. At the time, this discovery shocked the field of biology, as it called into question the 'immutable' nature of DNA, which was known to be the genetic material transmitted from generation to generation during the propagation of the species. Briefly describe this startling mechanism.
Antibody diversity is generated when each developing B cell undergoes a DNA rearrangement process. This process involves the combination of small gene segments, encoded as separate elements in the genome, to form a complete coding sequence for the antibody protein. As a result of this process, the DNA of the B cell is irrevocably altered, and would no longer be able to transmit all the genetic information to the next generation.
The antibody protein is often depicted as an uppercase letter Y, with the two variable regions (antigen-binding domains) pointing up, and the stem consisting of the Fc region (constant domain). An analogy has been made between an antibody protein and a guided missile, with one type of antibody domain functioning as the guidance system, and the other type of domain as the 'payload.' Which antibody domain serves as the guidance system, and which as the payload? Explain your answer.
Antibody variable domains form the antigen binding sites and serve as the guidance system. Specificity of these domains decides where the antibody protein binds, like directly on the pathogen or on a protein. Antibody binding alone has limited effects. For antibodies to function in pathogen/toxin elimination they use the Fc region as the payload. It is recognized by phagocytic cell receptors and aids in pathogen/toxin uptake or promotes complement activation. Without this payload, antibody proteins would only bind and have no effector functions.
Which of the following is required for T-cell activation?
Antigen-specific TCR binding to MHC peptide AND interaction with CD80, CD86, or ICOS-L
In influenza infections, _____ cause(s) milder and limited disease, whereas _____ cause(s) more severe disease and higher mortality.
Antigenic drift; antigenic shift
In 1918 ... The process of human influenza virus acquiring genes from other virus strains is called gene reassortment and it leads to
Antigenic shift
In 1918, a worldwide epidemic of influenza A resulted in the deaths of 40-50 million people. This strain of influenza A, known as H1N1 - - referring to the genotypes of the viral surface proteins, hemagglutinin (H) and neuraminidase (N) -- was shown to be derived from an avian virus that adapted to infect and grow in human cells. 2009 witnessed another H1N1 influenza pandemic. The 2009 influenza virus strain contained genes from avian and swine flu viruses that altered hemagglutinin and neuraminidase expression. The process of human influenza virus acquiring genes from other virus strains is called
Antigenic shift
Stimulation of the nucleic acid sensing TLRs that reside in endosomal membranes induces the production of a different cytokine response than is produced by stimulation of the plasma membrane TLRs. The cytokine response following stimulation of nucleic acid-sensing TLRs is characterized by production of:
Antiviral type I interferons
Which of the following statement does NOT apply to IgG?
Appears early in the primary immune response
Nuclease activity to open the DNA hairpin and generate P-nucleotides
Artemis
Formation of local immune complexes caused by IgG antibodies acting against an antigen in previously sensitized individuals
Arthus reaction
Recent studies using mouse models of pulmonary inflammation (a model for human asthma) have found that mice deficient in the C3a receptor have greatly reduced disease symptoms when challenged with inhaled preparations containing extracts of the fungal pathogen Aspergillus fumigatus. Specifically, the C3a receptor-deficient mice showed reduced influx of granulocytes and lymphocytes into the lung and reduced fluid in the lung after challenge. What is the explanation for these findings?
As complement is activated in the lung in response to the inhaled fungus, the C3 convertase makes C3a that induces a local inflammatory response. It does this by acting on vascular endothelial cells. The response includes increased vascular permeability that leads to more fluid in the lung and up-regulation of adhesion molecules on local vascular endothelium. This all results in increased recruitment of granulocytes, lymphocytes, and monocytes to the lung.
MASP2
Associates with MBL and cleaves C4
CXCL13
Attract B cells to B-cell zones in lymph nodes
Bonus effect of multivalent binding, results in "stronger" binding
Avidity
A correct statement regarding these data is: A. siRNA-1 and siRNA-3 target subunits of the IL-2 receptor but siRNA-2 does not. B. siRNA-2 targets a shared subunit of all three receptors, whereas siRNA-1 and siRNA-3 do not. C. siRNA-3 targets a subunit of the IL-7 receptor, but the other two siRNAs do not. D. siRNA-2 and siRNA-3 do not target a subunit of the IL-2 receptor. E. siRNA-2 targets a subunit shared by all receptors in the hematopoietin receptor superfamily.
B
Antibodies, complement proteins, and phagocytic cells provide effective protection against all of the following types of infections in Figure Q2.1, except:
B
Epithelial surfaces provide the first line of defense against infection by the use of several types of mechanisms. One of the chemical mechanisms used by epithelia is: A. Joining of epithelial cells by tight junctions B. Secretion of antimicrobial peptides by epithelial cells C. Production of mucus, tears, or saliva in the nose, eyes, and oral cavity D. Movement of mucus by cilia E. Peristalsis in the gastrointestinal tract
B
Inherited immunodeficiency diseases result from a single gene defect in one component of the immune system. By identifying the class of microbial pathogens a given immunodeficient individual becomes susceptible to, studies of these diseases indicate: A. Which type of antibiotics each patient should be given B. The essential immune mechanism required for resistance to each category of pathogen C. Whether the disease is a genetically inherited or an acquired form of immunodeficiency D. Whether the immunodeficiency disease is likely to be transmitted to another individual E. Whether the disease is likely to be life-threatening or not
B
Many of the inflammatory mediators produced by tissue macrophages at sites of infection act on the endothelial cells lining the blood vessel walls. An exception to this is (are) the: A. Cytokines that induce increased vascular permeability B. Chemokines that induce directed migration of blood monocytes C. Cytokines that induce increased expression of adhesion molecules D. TNF produced by tissue-resident sensor cells E. Bradykinin produced that causes pain
B
Multiple pathways for regulating complement activation limit the potential damage caused by complement deposition on host cells or caused by the spontaneous activation of complement proteins in the plasma. Genetic deficiencies in these mechanisms often lead to chronic inflammatory diseases, but in some cases can paradoxically lead to increased susceptibility to bacterial infections. This latter outcome may occur because: A. Complement regulatory proteins have dual functions in inhibiting and promoting complement activation. B. Uncontrolled complement activation leads to the depletion of serum complement proteins. C. The inhibition of the membrane attack complex by complement regulatory proteins normally leads to enhanced activation of the early steps of the complement pathway. D. Complement regulatory proteins normally cause the rapid depletion of plasma complement factors. E. Uncontrolled complement activation recruits the majority of phagocytic cells, leaving few remaining to fight infections in the tissues.
B
Several subsets of innate lymphoid cells (ILCs) have been identified that share their patterns of cytokine production with the known subsets of T cells. The combined activity of related ILC and T cell subsets is effective in eradicating pathogenic infections because: A. ILCs cannot kill the pathogen, whereas the antigen-specific T cells can kill the pathogen. B. The early response of ILCs that reside at the site of infection is followed by the later more robust response of pathogen-specific T cells that migrate to the site of infection. C. The ILCs activate B cells to induce antibody responses whereas the T cells are able to directly eliminate the pathogen. D. The ILCs are induced to migrate from the site of infection to the draining lymph nodes where they activate the antigen-specific T cells. E. The ILCs are activated to secrete antimicrobial compounds which cause them to lyse, releasing RNA and DNA that act on T cells to stimulate T cell cytotoxic activities.
B
Some Pattern Recognition Receptors (PRRs) recognize nucleic acids, like RNA or DNA. Since our own cells contain human RNA and DNA, the activation of innate immune pathways by these PRRs must rely on additional criteria to discriminate self from nonself. Additional criteria include everything EXCEPT: A. The subcellular location of the RNA B. The presence of adenosine residues in viral RNA C. The methylation state of the DNA D. Unique structures found on viral RNA E. The subcellular location of the DNA
B
Two strains of mice were infected with 5 10 4 PFU of Influenza A virus, and the survival data shown in Figure Q3.31 were obtained. Next, both strains were infected again with Influenza A, and levels of type I interferons (IFN- and IFN-) were measured and found to be similar between the two strains. Likewise, cells from both strains expressed similar levels of the IFN-/ receptor (IFNAR). Which of the following proteins might be more highly expressed in strain B than in strain A following Influenza A infection? A. MHC class I B. Mx-1 C. TLR4 D. Complement C3 E. ICAM-1
B
Antibodies, complement proteins, and phagocytic cells provide effective protection against all of the following types of infections in Figure Q2.1, except:
B need figure All extracellular forms of pathogens are targets for antibodies, complement, phagocytic cells and antibody-dependent immune clearance mechanisms. Once a pathogen, such as a virus or intracellular protozoan, invades a cell and begins replicating in the cell, these mechanisms are no longer able to clear the infection. These intracellular stages of pathogenic infection require cellular responses, such as those mediated by T cells or NK cells
1.13 Short answer: Most B and T lymphocytes in the circulation appear as small, inactive cells, with little cytoplasm, few cytoplasmic organelles, and nuclei containing condensed inactive chromatin. Yet these cells comprise the adaptive immune response, without which individuals die in infancy. What is the explanation for this apparent dichotomy?
B and T lymphocytes are a heterogeneous population, comprised of cells that each express a unique antigen receptor. As a consequence, only a small number of B and T lymphocytes will respond to any particular pathogenic infection. The vast majority of the circulating cells will never encounter the pathogen that binds to their antigen receptor; hence these cells remain in a naive, inactive state.
Most B and T lymphocytes in the circulation appear as small, inactive cells, with little cytoplasm, few cytoplasmic organelles, and nuclei containing condensed inactive chromatin. Yet these cells comprise the adaptive immune response, without which individuals die in infancy. What is the explanation for this apparent dichotomy?
B and T lymphocytes each express a unique antigen receptor, so only a small number of them will respond to any particular pathogenic infection. The majority of these cells won''t encounter their corresponding pathogen that binds to their antigen receptor, so they remain in an inactive state.
In a lymph node, which cells rely on follicular dendritic cell networks
B cells
While B cells and T cells differ markedly in their functions during an immune response, the two lymphocyte subsets share the enzymatic machinery and overall scheme for generating antigen receptor diversity. This is because
B cells and T cells both need enormous antigen receptor diversity to provide protection against the diversity of pathogens
While B cells and T cells differ markedly in their functions during an immune response, the two lymphocyte subsets share the enzymatic machinery and overall scheme for generating antigen receptor diversity. This is because:
B cells and T cells both need enormous antigen receptor diversity to provide protection against the diversity of pathogens.
In germinal centers, proliferating B cells undergo a process called somatic hypermutation, in which mutations are introduced into the V regions of the antibody heavy and light chain genes. When this process is complete after several weeks, the overall affinities of the antibodies produced are greatly increased compared to those present early in the primary response. The somatic hypermutation process leads to increased antibody affinity because:
B cells making higher affinity antibodies receive more help from TFH cells.
Borrelia hermsii is a spirochete bacterium, transmitted by tick bites, that causes an illness characterized by a relapsing fever. The bacteria enter the host bloodstream and replicate there. Studies in mice show that episodes of bacteremia (bacteria in the blood) are efficiently controlled by anti-bacterial antibodies, but interestingly, follicular B cells are not required for this response, nor is the response impaired by splenectomizing the mice (i.e., removing the spleen). Which B cells are most likely responsible for this antibody response?
B-1 B cells
Which types of mature B cells do not respond to a protein antigen
B-q and MZ B cells
Many of the inflammatory mediators produced by tissue macrophages at sites of infection act on the endothelial cells lining the blood vessel walls. An exception to this is (are) the: A. Cytokines that induce increased vascular permeability B. Chemokines that induce directed migration of blood monocytes C. Cytokines that induce increased expression of adhesion molecules D. TNF produced by tissue-resident sensor cells E. Bradykinin produced that causes pain
B. Most of the inflammatory mediators produced by tissue-resident macrophages in response to infection act on vascular endothelial cells to cause blood vessel dilation, leakiness of endothelial junctions allowing fluid and proteins to leak out of the blood, and induce increased expression of adhesion molecules on endothelial cells. In contrast, the chemokines that are produced act on the white blood cells adhering to the endothelium. These chemokines induce the blood cells, such as monocytes, to migrate across the endothelium into the tissue and then direct the cells toward the site of infection in the tissue.
Antibodies, complement proteins, and phagocytic cells provide effective protection against all of the following types of infections except: A. Fungi B. Virus-infected cell C. Worms D. Bacteria C. Viruses
B. All extracellular forms of pathogens are targets for antibodies, complement, phagocytic cells and antibody-dependent immune clearance mechanisms. Once a pathogen, such as a virus or intracellular protozoan, invades a cell and begins replicating in the cell, these mechanisms are no longer able to clear the infection. These intracellular stages of pathogenic infection require cellular responses, such as those mediated by T cells or NK cells.
Epithelial surfaces provide the first line of defense against infection by the use of several types of mechanisms. One of the chemical mechanisms used by epithelia is: A. Joining of epithelial cells by tight junctions B. Secretion of antimicrobial peptides by epithelial cells C. Production of mucus, tears, or saliva in the nose, eyes, and oral cavity D. Movement of mucus by cilia E. Peristalsis in the gastrointestinal tract
B. Anti-microbial peptides are produced by epithelia at all mucosal and epidermal surfaces. These chemicals are important in immune protection against microbial pathogens. All other choices are mechanical mechanisms by which surface epithelia protect against infections, not chemical mechanisms
Multiple pathways for regulating complement activation limit the potential damage caused by complement deposition on host cells or caused by the spontaneous activation of complement proteins in the plasma. Genetic deficiencies in these mechanisms often lead to chronic inflammatory diseases, but in some cases can paradoxically lead to increased susceptibility to bacterial infections. This latter outcome may occur because: A. Complement regulatory proteins have dual functions in inhibiting and promoting complement activation. B. Uncontrolled complement activation leads to the depletion of serum complement proteins. C. The inhibition of the membrane attack complex by complement regulatory proteins normally leads to enhanced activation of the early steps of the complement pathway. D. Complement regulatory proteins normally cause the rapid depletion of plasma complement factors. E. Uncontrolled complement activation recruits the majority of phagocytic cells, leaving few remaining to fight infections in the tissues.
B. Individuals with a genetic defect in factor I are subject to recurrent infections with pyogenic (pus-forming) extracellular bacterial infections. This occurs because, in the absence of factor I, uncontrolled complement activation ends up depleting the complement proteins from the plasma. This leads to impaired complement activation on these bacteria, and therefore, to diminished clearance of these infections.
1.17 Multiple choice: The antigen receptor on a T cell recognizes a degraded fragment of a protein (i.e., a peptide) bound to a specialized cell surface peptide-binding receptor called an MHC molecule. One key aspect of this system is that the peptides displayed on MHC molecules can be derived from intracellular proteins. This mode of antigen recognition is particularly important in allowing the adaptive immune response to detect infections by: A. Large helminthic parasites in the gastrointestinal tract B. Intracellular pathogens, such as viruses and some protozoa C. Extracellular bacteria that colonize the lungs D. Fungi that form hyphae in the bronchial airways E. Fungal infections in the skin epithelium
B. Intracellular pathogens, such as viruses and some protozoa, cannot be eliminated by antibody-based mechanisms once they have begun replicating in host cells. In order to detect these intracellular pathogens, a system that surveils the intracellular status of host cells is needed. T cells fulfill this function by recognizing peptides on cell surface MHC receptors. The MHC receptors can pick up pathogen-derived peptides from within the infected cell and display them on the cell surface for T cells to 'see.'
The classical complement pathway is initiated by C1q binding to the surface of a pathogen. In some cases, C1q can directly bind the pathogen, for instance by recognizing proteins of bacterial cell walls, but in most cases C1q binds to IgM antibodies that are bound to the pathogen surface. How does this IgM-binding feature of C1q contribute to rapid, innate immune responses rather than to slow, adaptive responses? A. C1q induces B lymphocytes to begin secreting antibody within hours of pathogen exposure. B. Natural antibody that binds to many microbial pathogens is produced prior to pathogen exposure. C. C1q binds to C-reactive protein which then binds to IgM on the pathogen surface. D. C1q directly induces inflammation, recruiting phagocytes and antibodies from the blood into the infected tissue. E. C1q binds to dendritic cells in the infected tissue, inducing them to secrete inflammatory cytokines.
B. Natural antibody, which is primarily of the IgM class, is produced in the body prior to pathogen exposure. These antibodies are widely reactive with many microbial pathogens, although they generally have low affinity for the pathogen. However, since IgM is a pentamer of IgM monomers, each IgM pentamer has 10 binding sites for antigen, allowing even low affinity antibodies to bind, due to the increased avidity of multiple binding sites. This natural antibody will then recruit C1q, leading to complement activation. Since the natural antibody pre-exists prior to pathogen exposure, this response is rapid and is considered part of the innate immune response.
1.32 Multiple choice: Several subsets of innate lymphoid cells (ILCs) have been identified that share their patterns of cytokine production with the known subsets of T cells. The combined activity of related ILC and T cell subsets is effective in eradicating pathogenic infections because: A. ILCs cannot kill the pathogen, whereas the antigen-specific T cells can kill the pathogen. B. The early response of ILCs that reside at the site of infection is followed by the later more robust response of pathogen-specific T cells that migrate to the site of infection. C. The ILCs activate B cells to induce antibody responses whereas the T cells are able to directly eliminate the pathogen. D. The ILCs are induced to migrate from the site of infection to the draining lymph nodes where they activate the antigen-specific T cells. E. The ILCs are activated to secrete antimicrobial compounds which cause them to lyse, releasing RNA and DNA that act on T cells to stimulate T cell cytotoxic activities.
B. The ILCs are components of the innate response, as they respond rapidly following encounter with pathogens, and in most cases, these cells are resident in mucosal tissues. In contrast, T cells are slow to respond and are found recirculating through the blood and secondary lymphoid organs prior to their activation by specific antigen. The ILCs are thus positioned for rapid responses to pathogens that breach the barrier, and the cytokines they produce help control the infection, allowing time for the adaptive response to be initiated. The T cell response is more robust, owing to the clonal expansion of antigen-specific T cells, and these cells then migrate to the site of infection. Once there, the T cells produce cytokines that amplify the response started by the ILCs.
Several subsets of innate lymphoid cells (ILCs) have been identified that share their patterns of cytokine production with the known subsets of T cells. The combined activity of related ILC and T cell subsets is effective in eradicating pathogenic infections because: A. ILCs cannot kill the pathogen, whereas the antigen-specific T cells can kill the pathogen. B. The early response of ILCs that reside at the site of infection is followed by the later more robust response of pathogen-specific T cells that migrate to the site of infection. C. The ILCs activate B cells to induce antibody responses whereas the T cells are able to directly eliminate the pathogen. D. The ILCs are induced to migrate from the site of infection to the draining lymph nodes where they activate the antigen-specific T cells. E. The ILCs are activated to secrete antimicrobial compounds which cause them to lyse, releasing RNA and DNA that act on T cells to stimulate T cell cytotoxic activities.
B. The ILCs are components of the innate response, as they respond rapidly following encounter with pathogens, and in most cases, these cells are resident in mucosal tissues. In contrast, T cells are slow to respond and are found recirculating through the blood and secondary lymphoid organs prior to their activation by specific antigen. The ILCs are thus positioned for rapid responses to pathogens that breach the barrier, and the cytokines they produce help control the infection, allowing time for the adaptive response to be initiated. The T cell response is more robust, owing to the clonal expansion of antigen-specific T cells, and these cells then migrate to the site of infection. Once there, the T cells produce cytokines that amplify the response started by the ILCs.
Some Pattern Recognition Receptors (PRRs) recognize nucleic acids, like RNA or DNA. Since our own cells contain human RNA and DNA, the activation of innate immune pathways by these PRRs must rely on additional criteria to discriminate self from nonself. Additional criteria include everything EXCEPT: A. The subcellular location of the RNA B. The presence of adenosine residues in viral RNA C. The methylation state of the DNA D. Unique structures found on viral RNA E. The subcellular location of the DNA
B. The presence of adenosine residues would not discriminate between viral and host RNA, as both types contain these residues.
1.38 Multiple choice: Inherited immunodeficiency diseases result from a single gene defect in one component of the immune system. By identifying the class of microbial pathogens a given immunodeficient individual becomes susceptible to, studies of these diseases indicate: A. Which type of antibiotics each patient should be given B. The essential immune mechanism required for resistance to each category of pathogen C. Whether the disease is a genetically inherited or an acquired form of immunodeficiency D. Whether the immunodeficiency disease is likely to be transmitted to another individual E. Whether the disease is likely to be life-threatening or not
B. The study of immunodeficiency diseases has been extremely informative about the essential mechanisms required for immune protection against different classes of pathogens. For instance, these studies have shown that individuals lacking B cells or antibodies are highly susceptible to extracellular bacterial infections, but have normal responses to most viral infections.
Inherited immunodeficiency diseases result from a single gene defect in one component of the immune system. By identifying the class of microbial pathogens a given immunodeficient individual becomes susceptible to, studies of these diseases indicate: A. Which type of antibiotics each patient should be given B. The essential immune mechanism required for resistance to each category of pathogen C. Whether the disease is a genetically inherited or an acquired form of immunodeficiency D. Whether the immunodeficiency disease is likely to be transmitted to another individual E. Whether the disease is likely to be life-threatening or not
B. The study of immunodeficiency diseases has been extremely informative about the essential mechanisms required for immune protection against different classes of pathogens. For instance, these studies have shown that individuals lacking B cells or antibodies are highly susceptible to extracellular bacterial infections, but have normal responses to most viral infections.
Using an antibody that recognizes the phosphorylated, but not the non-phosphorylated form of the transcription factor, NFAT, T cells are permeabilized, stained with this antibody, and analyzed by flow cytometry. Which of the data in Figure Q7.15 represent the expected pattern of staining from wild-type T cells before and after TCR stimulation.
B. (red peak is to the left of gray peak)
Multiple choice: The MARCH-1 E3-ubiquitin ligase is expressed in B cells, dendritic cells, and macrophages. The pathway regulated by MARCH-1 is targeted by some pathogens in an immune evasion strategy. In this strategy, the pathogens encode: A. A protein that induces degradation of MARCH-1 B. A protein that mimics MARCH-1 and functions similarly C. A protein that binds to MARCH-1 and inhibits its function D. A protein that is induced by IL-10 in macrophages and dendritic cells E. A protein that induces degradation of CD86
B. A protein that mimics MARCH-1 and functions similarly
Complement component C3 is cleaved by A.C1r and C1s B.C3bBb C.Factor B D.Factor D E.MASP
B. C3bBb
The cellular distribution of MHC class I versus MHC class II molecules is quite different, with MHC class II molecules generally expressed on a very limited set of cell types. This is because: A. It would be detrimental to have CD8 T cells killing macrophages or B cells. B. CD4 T cells generally secrete cytokines that act on macrophages and B cells. C. Viruses generally do not infect and replicate in macrophages and B cells. D. Dendritic cells are more important in stimulating CD4 than CD8 T cell responses. E. CD4 T cells can only kill macrophages, dendritic cells, and B cells.
B. CD4 T cells generally secrete cytokines that act on macrophages and B cells
Multiple choice: The cellular distribution of MHC class I versus MHC class II molecules is quite different, with MHC class II molecules generally expressed on a very limited set of cell types. This is because: A. It would be detrimental to have CD8 T cells killing macrophages or B cells. B. CD4 T cells generally secrete cytokines that act on macrophages and B cells. C. Viruses generally do not infect and replicate in macrophages and B cells. D. Dendritic cells are more important in stimulating CD4 than CD8 T cell responses. E. CD4 T cells can only kill macrophages, dendritic cells, and B cells.
B. CD4 T cells generally secrete cytokines that act on macrophages and B cells.
Multiple choice: Many of the inflammatory mediators produced by tissue macrophages at sites of infection act on the endothelial cells lining the blood vessel walls. An exception to this is (are) the: A. Cytokines that induce increased vascular permeability B. Chemokines that induce directed migration of blood monocytes C. Cytokines that induce increased expression of adhesion molecules D. TNF produced by tissue-resident sensor cells E. Bradykinin produced that causes pain
B. Chemokines that induce directed migration of blood monocytes
Human patients with genetic defects that result in a failure to produce the calcium channel protein ORAI1, or the ER calcium sensor protein STIM1, have severe immunodeficiency diseases. An immunosuppressive drug that would most closely mimic these primary immunodeficiencies is: A. Rituximab, a drug that depletes B cells B. Cyclosporin A, a calcineurin inhibitor C. Rapamycin, an mTOR inhibitor D. Tysabri, an inhibitor of integrin binding E. Enbrel or Humira that inhibit TNF
B. Cyclosporin A, a calcineurin inhibitor
Amino acid sequence analysis of all of the peptides found in a single IgG antibody would reveal unique peptide sequences totaling ~600-700 amino acids. Using this estimate, the predicted molecular weight of an antibody protein would be ~70-75 kDa. Yet, an intact antibody protein has a molecular weight of ~150 kDa. The explanation for this discrepancy is: A. IgG antibodies have many more heavy amino acids in them than most other proteins. B. Each IgG antibody is a complex of two identical light chains and two identical heavy chains. C. IgG antibodies tend to aggregate together during purification, thereby distorting molecular weight estimates. D. Each IgG antibody is a complex of four identical polypeptides. E. IgG antibodies are produced as dimers of two identical IgG monomers.
B. Each IgG antibody is a complex of two identical light chains and two identical heavy chains
Multiple choice: Amino acid sequence analysis of all of the peptides found in a single IgG antibody would reveal unique peptide sequences totaling ~600-700 amino acids. Using this estimate, the predicted molecular weight of an antibody protein would be ~70-75 kDa. Yet, an intact antibody protein has a molecular weight of ~150 kDa. The explanation for this discrepancy is: A. IgG antibodies have many more heavy amino acids in them than most other proteins. B. Each IgG antibody is a complex of two identical light chains and two identical heavy chains. C. IgG antibodies tend to aggregate together during purification, thereby distorting molecular weight estimates. D. Each IgG antibody is a complex of four identical polypeptides. E. IgG antibodies are produced as dimers of two identical IgG monomers.
B. Each IgG antibody is a complex of two identical light chains and two identical heavy chains.
All of the modular protein domains used for signaling protein interactions bind to ligands that are transiently generated following receptor stimulation. A. True B. False
B. False
Diacyl-glycerol (DAG) is one of the two products generated when PLC- cleaves the membrane phospholipid, PIP2. This small lipid mediator remains associated with the plasma membrane and functions to inhibit tyrosine phosphatases that remove activating phosphate groups from ZAP-70 and the Tec-family kinase, ITK. A. True B. False
B. False
Following TCR or BCR signaling, the most important events downstream of the activation of ZAP-70 or SYK, respectively, are the activation of transcription factors leading to new gene expression. A. True B. False
B. False
Like innate sensors of infections (TLRs, NLRs, RLRs), antibodies frequently recognize nucleic acids of pathogenic organisms. A. True B. False
B. False
Mucosal surfaces and external epithelia are major routes of pathogenic infection. Mucosal surfaces are found in tissues such as the gastrointestinal tract, the reproductive tract and the mouth and respiratory tract. While the mouth and respiratory tract are routes of virus but not bacterial infections, the gastrointestinal tract is the route for bacterial but not virus infections. A. True B. False
B. False
Several small GTPases play critical roles in antigen receptor signaling pathways. When activated by binding to GTP, these mediators induce changes in cytoskeletal organization, adhesion, and metabolism, but have no role in transcription factor activation. A. True B. False
B. False
The C3 convertase amplifies the process of complement activation by generating large amounts of C3b and cleaving large numbers of C5 molecules. A. True B. False
B. False
The antibody protein has two functional domains, one for antigen binding and a second to confer specific effector functions. These two functional domains are encoded by the antibody light chain and antibody heavy chain polypeptides, respectively. A. True B. False
B. False
The classical and lectin pathways of complement activation converge at the step of C3 activation. However, the initiating steps of each pathway use protein components and enzymatic mechanisms that share no similarity with each other. A. True B. False
B. False
The mechanism by which CTLA-4 inhibits T cell activation is by recruiting inhibitory phosphatases. A. True B. False
B. False
The only mechanism by which CD28 co-stimulation enhances T cell activation is by recruiting and activating PI 3-kinase, leading to Akt activation. A. True B. False
B. False
Unlike TCR signaling, B cell receptor (BCR) signaling is not initiated by a Src-family kinase phosphorylating tyrosine resides in ITAM motifs of BCR signaling subunits. A. True B. False
B. False
n patients with 'CD40 ligand deficiency', T cell-dependent B cell activation is impaired, leading to poor antibody responses to protein antigens. The signaling pathway missing in these patients' B cells is important for: A. Inducing integrin activation to promote adhesion B. Inducing NFkB activation by the noncanonical pathway C. Inducing WASp activation and actin polymerization D. Inducing Ca2+ influx leading to NFAT activation E. Inducing Ras activation and Erk Map-kinase signaling
B. Inducing NFkB activation by the noncanonical pathway
Multiple choice: The antigen receptor on a T cell recognizes a degraded fragment of a protein (i.e., a peptide) bound to a specialized cell surface peptide-binding receptor called an MHC molecule. One key aspect of this system is that the peptides displayed on MHC molecules can be derived from intracellular proteins. This mode of antigen recognition is particularly important in allowing the adaptive immune response to detect infections by: A. Large helminthic parasites in the gastrointestinal tract B. Intracellular pathogens, such as viruses and some protozoa C. Extracellular bacteria that colonize the lungs D. Fungi that form hyphae in the bronchial airways E. Fungal infections in the skin epithelium
B. Intracellular pathogens, such as viruses and some protozoa
The antigen receptor on a T cell recognizes a degraded fragment of a protein (i.e., a peptide) bound to a specialized cell surface peptide-binding receptor called an MHC molecule. One key aspect of this system is that the peptides displayed on MHC molecules can be derived from intracellular proteins. This mode of antigen recognition is particularly important in allowing the adaptive immune response to detect infections by: A. Large helminthic parasites in the gastrointestinal tract B. Intracellular pathogens, such as viruses and some protozoa C. Extracellular bacteria that colonize the lungs D. Fungi that form hyphae in the bronchial airways E. Fungal infections in the skin epithelium
B. Intracellular pathogens, such as viruses and some protozoa.
Multiple choice: In spite of their low affinity for binding to their antigen, IgM antibodies can be quite effective at promoting the elimination of extracellular bacterial infections. This is due to: A. The ability of IgM antibodies to traffic across epithelial surfaces B. Multivalent binding of IgM pentamers to repetitive epitopes on bacterial surfaces C. The high concentration of IgM antibodies in the serum and in all tissues D. The early production of IgM antibodies during an immune response E. The high rate of somatic hypermutation in the genes encoding IgM antibodies
B. Multivalent binding of IgM pentamers to repetitive epitopes on bacterial surfaces
Multiple choice: Two strains of mice were infected with 5x10^4 PFU of Influenza A virus, and the survival data shown in Figure Q3.31 were obtained. (FIGURE) Next, both strains were infected again with Influenza A, and levels of type I interferons were measured and found to be similar between the two strains. Likewise, cells from both strains expressed similar levels of the IFN-alpha/beta receptor (IFNAR). Which of the following proteins might be more highly expressed in strain B than in strain A following Influenza A infection? A. MHC class I B. Mx-1 C. TLR4 D. Complement C3 E. ICAM-1
B. Mx-1
Multiple choice: The classical complement pathway is initiated by C1q binding to the surface of a pathogen. In some cases, C1q can directly bind the pathogen, for instance by recognizing proteins of bacterial cell walls, but in most cases C1q binds to IgM antibodies that are bound to the pathogen surface. How does this IgM-binding feature of C1q contribute to rapid, innate immune responses rather than to slow, adaptive responses? A. C1q induces B lymphocytes to begin secreting antibody within hours of pathogen exposure. B. Natural antibody that binds to many microbial pathogens is produced prior to pathogen exposure. C. C1q binds to C-reactive protein which then binds to IgM on the pathogen surface. D. C1q directly induces inflammation, recruiting phagocytes and antibodies from the blood into the infected tissue. E. C1q binds to dendritic cells in the infected tissue, inducing them to secrete inflammatory cytokines.
B. Natural antibody that binds to many microbial pathogens is produced prior to pathogen exposure.
The classical complement pathway is initiated by C1q binding to the surface of a pathogen. In some cases, C1q can directly bind the pathogen, for instance by recognizing proteins of bacterial cell walls, but in most cases C1q binds to IgM antibodies that are bound to the pathogen surface. How does this IgM-binding feature of C1q contribute to rapid, innate immune responses rather than to slow, adaptive responses? A. C1q induces B lymphocytes to begin secreting antibody within hours of pathogen exposure. B. Natural antibody that binds to many microbial pathogens is produced prior to pathogen exposure. C. C1q binds to C-reactive protein which then binds to IgM on the pathogen surface. D. C1q directly induces inflammation, recruiting phagocytes and antibodies from the blood into the infected tissue. E. C1q binds to dendritic cells in the infected tissue, inducing them to secrete inflammatory cytokines.
B. Natural antibody that binds to many microbial pathogens is produced prior to pathogen exposure.
Multiple choice: Some viruses have mechanisms to down-regulate MHC class I protein expression on the surface of cells in which the virus is replicating. This immune evasion strategy might prevent effector CD8 cytotoxic T cells from recognizing and killing the virus-infected cells. Would this immune evasion strategy also prevent the initial activation of virus-specific CD8 T cells? A. Yes, because no viral peptide:MHC class I complexes would form to activate CD8 T cells. B. No, because dendritic cells would take up infected cells and cross-present viral peptides to activate CD8 T cells. C. No, because some presentation of MHC class I complexes with viral peptides would occur before the virus could down-regulate all the surface MHC class I protein. D. Yes, because this immune evasion strategy would also function in dendritic cells, even if the virus doesn't replicate in dendritic cells. E. No, because the type I interferon response induced by the virus infection will up- regulate MHC class I expression and override the immune evasion mechanism.
B. No, because dendritic cells would take up infected cells and cross-present viral peptides to activate CD8 T cells.
Multiple choice: In rare instances, B cells can be found that have two immunoglobulin light chain alleles, both of which are rearranged in frame, and can encode functional light chain proteins. Yet, on the surface of the B cell, only one of the two light chain proteins is detected in the membrane-bound immunoglobulin receptor. The reason these rare cells have two functional light chain rearrangements but only express one of the two light chains as part of the B-cell receptor is: A. One of the two light chains is formed from rearrangement of a V gene segment that is a pseudogene. B. One of the two light chain proteins doesn't form a stable complex with the heavy chain expressed in this cell. C. One of the two light chain alleles is not transcribed efficiently, and produces only low levels of protein. D. One of the two light chain alleles uses a V gene segment that is not targeted very often by the RAG recombinase. E. One of the two light chains is rapidly degraded after synthesis due to improper folding.
B. One of the two light chain proteins doesn't form a stable complex with the heavy chain expressed in this cell.
Epithelial surfaces provide the first line of defense against infection by the use of several types of mechanisms. One of the chemical mechanisms used by epithelia is: A. Joining of epithelial cells by tight junctions B. Secretion of antimicrobial peptides by epithelial cells C. Production of mucus, tears, or saliva in the nose, eyes, and oral cavity D. Movement of mucus by cilia E. Peristalsis in the gastrointestinal tract
B. Secretion of antimicrobial peptides by epithelial cells
Epithelial surfaces provide the first line of defense against infection by the use of several types of mechanisms. One of the chemical mechanisms used by epithelia is: A.Joining of epithelial cells by tight junctions B.Secretion of antimicrobial peptides by epithelial cells C.Production of mucus, tears, or saliva in the nose, eyes, and oral cavity D.Movement of mucus by cilia E.Peristalsis in the gastrointestinal tract
B. Secretion of antimicrobial peptides by epithelial cells
Multiple choice: Epithelial surfaces provide the first line of defense against infection by the use of several types of mechanisms. One of the chemical mechanisms used by epithelia is: A. Joining of epithelial cells by tight junctions B. Secretion of antimicrobial peptides by epithelial cells C. Production of mucus, tears, or saliva in the nose, eyes, and oral cavity D. Movement of mucus by cilia E. Peristalsis in the gastrointestinal tract
B. Secretion of antimicrobial peptides by epithelial cells
Multiple choice: T cells expressing delta:gamma T-cell receptors have been found to recognize a diversity of ligands, including pathogen-derived proteins, self-peptides, and stress- induced molecules. This pattern of antigen recognition shows similarity to that of iNKT cells and MAIT cells, suggesting that delta:gamma T cells: A. Do not play an important role in immunity, but likely have a non-immune function B. Share features of both innate and adaptive immune cells C. Are only able to respond when the host is infected with a virus such as herpes simplex virus D. Are involved in maintaining the integrity of endothelial cells in the host E. Are most important in responses to tumor cells that show stress responses
B. Share features of both innate and adaptive immune cells
Immunoreceptor signaling proteins, such as the TCR chain and CD3 subunits, have conserved ITAM motifs in their cytoplasmic tails. When fully phosphorylated, the ITAM recruits a tyrosine kinase with a tandem SH2 domain structure at the amino-terminal end of the protein. Tandem SH2 domain-containing kinases do not bind to sequences in other proteins, even if they contain a phosphorylated tyrosine because: A. The amino acid sequence adjacent to the phosphorylated tyrosines in the ITAM motif is unique, and not found in any other proteins. B. The affinity of a single SH2 domain within these kinases for a tyrosine phosphorylated sequence is too low for efficient binding. C. The amino-terminal SH2 domain of the kinase has very high affinity for both of the phosphorylated tyrosines in the ITAM motif, so will not bind to other proteins. D. The amino-terminal SH2 domain of the kinase is in an autoinhibited conformation and can only bind to a phosphorylated ITAM. E. The tandem SH2 domain-containing kinase phosphorylates the tyrosines in the ITAM itself, so can only bind to these sequences.
B. The affinity of a single SH2 domain within these kinases for a tyrosine phosphorylated sequence is too low for efficient binding.
Multiple choice: Several subsets of innate lymphoid cells (ILCs) have been identified that share their patterns of cytokine production with the known subsets of T cells. The combined activity of related ILC and T cell subsets is effective in eradicating pathogenic infections because: A. ILCs cannot kill the pathogen, whereas the antigen-specific T cells can kill the pathogen. B. The early response of ILCs that reside at the site of infection is followed by the later more robust response of pathogen-specific T cells that migrate to the site of infection. C. The ILCs activate B cells to induce antibody responses whereas the T cells are able to directly eliminate the pathogen. D. The ILCs are induced to migrate from the site of infection to the draining lymph nodes where they activate the antigen-specific T cells. E. The ILCs are activated to secrete antimicrobial compounds which cause them to lyse, releasing RNA and DNA that act on T cells to stimulate T cell cytotoxic activities.
B. The early response of ILCs that reside at the site of infection is followed by the later more robust response of pathogen-specific T cells that migrate to the site of infection.
Several subsets of innate lymphoid cells (ILCs) have been identified that share their patterns of cytokine production with the known subsets of T cells. The combined activity of related ILC and T cell subsets is effective in eradicating pathogenic infections because: A. ILCs cannot kill the pathogen, whereas the antigen-specific T cells can kill the pathogen. B. The early response of ILCs that reside at the site of infection is followed by the later more robust response of pathogen-specific T cells that migrate to the site of infection. C. The ILCs activate B cells to induce antibody responses whereas the T cells are able to directly eliminate the pathogen. D. The ILCs are induced to migrate from the site of infection to the draining lymph nodes where they activate the antigen-specific T cells. E. The ILCs are activated to secrete antimicrobial compounds which cause them to lyse, releasing RNA and DNA that act on T cells to stimulate T cell cytotoxic activities.
B. The early response of ILCs that reside at the site of infection is followed by the later more robust response of pathogen-specific T cells that migrate to the site of infection.
Multiple choice: Inherited immunodeficiency diseases result from a single gene defect in one component of the immune system. By identifying the class of microbial pathogens a given immunodeficient individual becomes susceptible to, studies of these diseases indicate: A. Which type of antibiotics each patient should be given B. The essential immune mechanism required for resistance to each category of pathogen C. Whether the disease is a genetically inherited or an acquired form of immunodeficiency D. Whether the immunodeficiency disease is likely to be transmitted to another individual E. Whether the disease is likely to be life-threatening or not
B. The essential immune mechanism required for resistance to each category of pathogen
Inherited immunodeficiency diseases result from a single gene defect in one component of the immune system. By identifying the class of microbial pathogens a given immunodeficient individual becomes susceptible to, studies of these diseases indicate: A. Which type of antibiotics each patient should be given B. The essential immune mechanism required for resistance to each category of pathogen C. Whether the disease is a genetically inherited or an acquired form of immunodeficiency D. Whether the immunodeficiency disease is likely to be transmitted to another individual E. Whether the disease is likely to be life-threatening or not
B. The essential immune mechanism required for resistance to each category of a pathogen
Multiple choice: The formation of the C3 convertase is a key step in complement activation that occurs in all three complement pathways. This enzyme cleaves C3 in blood plasma, leading to a conformational change in the C3b fragment that exposes its reactive thioester group. The activated C3b is potentially harmful to the host, if it becomes covalently attached to a host cell, rather than to the surface of a pathogen. This deleterious outcome is largely avoided by: A. The inability of active C3b to diffuse away in the blood plasma. B. The inability of active C3b to covalently attach to the membranes of eukaryotic cells. C. The rapid hydrolysis of active C3b in solution, rendering it inactive. D. The tight binding of active C3b to the C3 convertase. E. The ability of active C3b to recruit phagocytic cells.
B. The inability of active C3b to covalently attach to the membranes of eukaryotic cells.
Lymphocyte activation leads to robust proliferation and effector cell differentiation. The metabolic demands of these processes are met, in part, by up-regulation of glycolytic enzymes and nutrient transporters on the activated cell membrane. A key intermediate in the signaling pathway leading to enhanced glucose metabolism following antigen receptor stimulation is: A. The lipid mediator diacyl-glycerol (DAG) B. The phosphoinositide, PIP3 C. Increases in cytoplasmic Ca2+ D. Cleavage of the membrane phospholipid, PIP2 E. The mitochondrial protein, Bcl-2
B. The phosphoinositide, PIP3
Multiple choice: Some Pattern Recognition Receptors (PRRs) recognize nucleic acids, like RNA or DNA. Since our own cells contain human RNA and DNA, the activation of innate immune pathways by these PRRs must rely on additional criteria to discriminate self from nonself. Additional criteria include everything EXCEPT: A. The subcellular location of the RNA B. The presence of adenosine residues in viral RNA C. The methylation state of the DNA D. Unique structures found on viral RNA E. The subcellular location of the DNA
B. The presence of adenosine residues in viral RNA
Some Pattern Recognition Receptors (PRRs) recognize nucleic acids, like RNA or DNA. Since our own cells contain human RNA and DNA, the activation of innate immune pathways by these PRRs must rely on additional criteria to discriminate self from nonself. Additional criteria include everything EXCEPT: A. The subcellular location of the RNA B. The presence of adenosine residues in viral RNA C. The methylation state of the DNA D. Unique structures found on viral RNA E. The subcellular location of the DNA
B. The presence of adenosine residues in viral RNA
Mannose binding lectins (MBL) and ficolins are the two classes of proteins that can initiate the lectin pathway of complement activation. These proteins are selective for activating complement on the surfaces of microbial pathogens rather than host cells because: A.Their higher-order oligomeric structure can be assembled only after the monomers first bind to pathogen membranes. B.They only recruit MASP (MBL-associated serine proteases) proteins when bound to pathogen surfaces and not when bound to host cells. C.They only undergo the conformational change needed to activate MASP proteins when bound to a pathogen and not when bound to a host cell. D.They only bind to carbohydrate side chains and oligosaccharide modifications found on pathogen surfaces but not on host cell membranes. E.The activated MASP proteins are rapidly inactivated by hydrolysis when present on the surface of a host cell.
B. They only recruit MASP (MBL-associated serine proteases) proteins when bound to pathogen surfaces, and not when bound to host cells
Multiple choice: The exon encoding the V region of an immunoglobulin protein is generated by a process of somatic recombination. This recombination event brings V gene and J gene segments together: A. In all cells of the body to encode a V region sequence B. To generate maximum diversity in the CDR3 sequence of the V region C. By alternative RNA splicing to encode a V region sequence D. By a precise mechanism that never adds or loses nucleotides at the junction E. To generate a single exon encoding the entire immunoglobulin protein
B. To generate maximum diversity in the CDR3 sequence of the V region
Multiple pathways for regulating complement activation limit the potential damage caused by complement deposition on host cells or caused by the spontaneous activation of complement proteins in the plasma. Genetic deficiencies in these mechanisms often lead to chronic inflammatory diseases, but in some cases can paradoxically lead to increased susceptibility to bacterial infections. This latter outcome may occur because: A. Complement regulatory proteins have dual functions in inhibiting and promoting complement activation. B. Uncontrolled complement activation leads to the depletion of serum complement proteins. C. The inhibition of the membrane attack complex by complement regulatory proteins normally leads to enhanced activation of the early steps of the complement pathway. D. Complement regulatory proteins normally cause the rapid depletion of plasma complement factors. E. Uncontrolled complement activation recruits the majority of phagocytic cells, leaving few remaining to fight infections in the tissues.
B. Uncontrolled complement activation leads to the depletion of serum complement proteins
Multiple choice: Multiple pathways for regulating complement activation limit the potential damage caused by complement deposition on host cells or caused by the spontaneous activation of complement proteins in the plasma. Genetic deficiencies in these mechanisms often lead to chronic inflammatory diseases, but in some cases can paradoxically lead to increased susceptibility to bacterial infections. This latter outcome may occur because: A. Complement regulatory proteins have dual functions in inhibiting and promoting complement activation. B. Uncontrolled complement activation leads to the depletion of serum complement proteins. C. The inhibition of the membrane attack complex by complement regulatory proteins normally leads to enhanced activation of the early steps of the complement pathway. D. Complement regulatory proteins normally cause the rapid depletion of plasma complement factors. E. Uncontrolled complement activation recruits the majority of phagocytic cells, leaving few remaining to fight infections in the tissues.
B. Uncontrolled complement activation leads to the depletion of serum complement proteins.
Individuals or mice with defects in the biochemical pathways needed for loading peptides onto MHC molecules show greatly increased susceptibility to virus infections. Experiments examining the MHC molecules present on the surface of host cells in these individuals would show: A. Normal numbers of MHC molecules expressed on host cells, but no peptides bound to them. B. Very low levels of total MHC proteins expressed on the cell surface. C. Normal numbers of MHC proteins on the surface but all of them bound to self-peptides not pathogen peptides. D. Very high levels of total MHC proteins expressed on the cell surface. E. Only virus-infected cells expressing high levels of MHC proteins on the cell surface.
B. Very low levels of total MHC proteins expressed on the cell surface
Multiple choice: Individuals or mice with defects in the biochemical pathways needed for loading peptides onto MHC molecules show greatly increased susceptibility to virus infections. Experiments examining the MHC molecules present on the surface of host cells in these individuals would show: A. Normal numbers of MHC molecules expressed on host cells, but no peptides bound to them. B. Very low levels of total MHC proteins expressed on the cell surface. C. Normal numbers of MHC proteins on the surface but all of them bound to self- peptides not pathogen peptides. D. Very high levels of total MHC proteins expressed on the cell surface. E. Only virus-infected cells expressing high levels of MHC proteins on the cell surface.
B. Very low levels of total MHC proteins expressed on the cell surface.
Multiple choice: Antibodies, complement proteins, and phagocytic cells provide effective protection against all of the following types of infections in Figure Q2.1, except (SEE FIGURE): A. Fungi B. Virus-infected cell C. Worms D. Bacteria E. Viruses
B. Virus-infected cell
Multiple choice: To identify genes encoding the receptors for the cytokines IL-2, IL-4, and IL-7, an siRNA screen is performed using purified T lymphocytes. To identify siRNAs that knock-down cytokine receptor expression, the T cells have been transfected with a construct that produces green fluorescent protein (GFP) when any one of these three cytokines is used to stimulate the cells. When the screen is completed, several different siRNAs have been identified that substantially reduce the T cells ability to respond to these cytokines as shown in Figure Q3.22. A correct statement regarding these data is: A. siRNA-1 and siRNA-3 target subunits of the IL-2 receptor but siRNA-2 does not. B. siRNA-2 targets a shared subunit of all three receptors, whereas siRNA-1 and siRNA-3 do not. C. siRNA-3 targets a subunit of the IL-7 receptor, but the other two siRNAs do not. D. siRNA-2 and siRNA-3 do not target a subunit of the IL-2 receptor. E. siRNA-2 targets a subunit shared by all receptors in the hematopoietin receptor superfamily.
B. siRNA-2 targets a shared subunit of all three receptors, whereas siRNA-1 and siRNA-3 do not.
When a naïve T cell recognizes peptide:MHC complex on an APC, the T cell shows activation responses, including the up-regulation of multiple genes. For the T cell to undergo robust proliferation, which of the following signals are required?
B7 family ligands
Purified naive T cells isolated from a T-cell receptor transgenic mouse represent a homogeneous population of cells with specificity for a single known peptide:MHC complex. This specific peptide:MHC complex can be purified and formed into multivalent complexes, such as peptide:MHC tetramers. When the naive T cells are stimulated with their 'antigen' in the form of these peptide:MHC tetramers, the T cells show activation responses, including the up-regulation of genes that are induced within several hours after T-cell receptor stimulation. However, these activated T cells fail to undergo robust proliferation, and the majority of cells die after 3-4 days in culture. T cell proliferation and survival could be greatly augmented by addition of:
B7 ligands for CD28
When a naive T cell recognizes peptide:MHC complex on an APC, the T cell shows activation responses, including the up-regulation of multiple genes. For the T cell to undergo robust proliferation, which of the following signals are required?
B7 ligands for CD28
Which class of cell surface receptors is NOT directly encoded in the germline?
BCR
Which of the following classes of cell surface receptors is NOT directly encoded in the germline?
BCR
Which of the following mechanisms of mutagenesis mediated by AID activity is possible? Select all that apply.
Base excision repair, followed by error-prone DNA polymerase fill-in of the gap created. Mismatch repair, followed by error-prone DNA polymerase fill-in of the gap created. The lesion is not repaired prior to replication, resulting in a CG→TA transition.
How does C1 allow the CLASSICAL PATHWAY to function in both the innate immunity and adaptive immunity?
Because C1 can interact with pathogens and antibodies. This is what allows the classical pathway to function in both the innate immunity and adaptive immunity.
Why does RegIIIα s preferentially kill Gram-positive bacteria?
Because the Lipopolysaccharides (LPS) of Gram-negative bacteria inhibits the pore-forming ability of RegIIIα, further enforcing the selectivity of RegIII proteins for Gram-positive bacteria.
All blood cells in an adult human can trace their ancestry to which compartment within the body?
Bone marrow
While many cell types in the thymus are able to induce negative selection of developing self-reactive thymocytes, bone marrow-derived antigen-presenting cells, such as macrophages and dendritic cells, appear to be the most important for this process. One likely reason for the prominent role of bone marrow-derived antigen-presenting cells in inducing negative selection of developing thymocytes is:
Bone marrow-derived antigen-presenting cells are highly phagocytic and have specialized mechanisms for presenting peptides on both MHC class I and class II.
Which of the following statements is TRUE about B-1 B cells and MZB cells? Select all that apply.
Both are self-renewing in the periphery, not requiring replacement from bone marrow. Both can respond to TI antigens Both predominantly produce IgM
Peptide binding diversity is increased by
Both multiple MHC alleles in the population and multiple homologous MHC genes in the genome
Members of type I and type III interferon are responsible for controlling:
Both proliferation of infected host cells AND viral replication within host cells
Bruton's X-linked agammaglobulinemia (XLA) results from a mutation in:
Bruton's tyrosine kinase (Btk)
As a family, TLRs can recognize PAMPs associated with a broad array of different pathogens, including bacteria, viruses, and fungi. Patients with a specific susceptibility to herpesvirus infections have a defect in their ability to respond to viral nucleic acids using TLR-3, TLR-7, or TLR-9, even though these proteins are expressed in the patients' cells. Analysis of the TLRs in macrophages and dendritic cells from these patients would likely show which of the arrangements in Figure Q3.11?
C
Cytokine receptors of the hematopoietin superfamily engage signaling pathways that begin with JAK kinases and lead to activation of STAT-family transcription factors. Each receptor subunit in this superfamily binds a specific JAK kinase (one of four members) and each receptor complex usually activates one major STAT homodimer (one of seven). The specificity for activation of one STAT homodimer by each cytokine is determined by: A. The specificity of each JAK kinase for only phosphorylating one or two out of the seven possible STAT members B. The specificity of each cytokine receptor complex to only activate one of the four Jak kinase members, which then homodimerizes C. The amino acid sequence surrounding the phosphorylated tyrosine on each cytokine receptor subunit's cytoplasmic tail D. The expression of only one STAT member in each type of immune cell, depending on which cytokine receptors are expressed E. The inhibition of all but one STAT protein by the inhibitor SOCS proteins expressed in each cell type
C
Dendritic cells in the skin, known as Langerhans cells, express very high levels of the NOD-like receptor, NLRP3. Previous studies showed that treatment of these cells with the Staphylococcus aureus pore-forming toxin causes K + efflux from the cells. To investigate whether this signal could induce IL-1 (an inflammatory cytokine) secretion by the cells, the following study (Figure Q3.16) was performed: Figure Q3.16 The explanation for these results is: A. NLRP3 is not activated by K + efflux from the cells. B. The S. aureus toxin does not kill the Langerhans cells. C. The live S. aureus bacteria activate a TLR and NLRP3. D. The S. aureus membrane prep does not contain a TLR ligand. E. TLR activation by S. aureus membranes induces interferon production.
C
Even when the complement cascade fails to proceed beyond generating the C3 convertase, complement activation is effective at inducing pathogen uptake and destruction. This process of immune protection is mediated by: A. Activation of complement inhibitory receptors on phagocytes that promote pathogen uptake B. Activation of soluble proteases in the serum that disrupt pathogen membranes C. Engagement of complement receptors on phagocytes by C3b and its cleavage products which promotes phagocytosis D. Engagement of complement receptors on B cells that promotes antibody production E. Stimulation of antimicrobial peptide secretion by phagocytes
C
NK cells express receptors from several families, each of which has multiple members. Some of these receptors are activating and others are inhibitory, and NK cell activation is dependent on the balance of signaling overall. The individual NK cells in an individual: A. Always express a majority of activating versus inhibitory receptors B. Are more potent effectors of cytotoxicity than of cytokine-production C. Each express only a subset of all possible NK receptors D. Are not considered members of the innate lymphoid cell lineage E. Undergo massive proliferation in response to infection, similar to T lymphocytes
C
Naive B and T lymphocytes are small, quiescent cells with little cytoplasm and low metabolic activity. Yet within hours after being activated following encounter with their antigen, these cells enlarge and up-regulate many biosynthetic and metabolic pathways. Approximately one day later, the cells begin dividing, and for several days they are the most rapidly dividing cells in the body, undergoing 2-4 rounds of cell division every day. In order to maintain this phenomenal rate of cell division, lymphoblasts must: A. Use the large energy stores accumulated by them when they were naive quiescent cells prior to their activation B. Engulf their neighboring small quiescent lymphocytes in order to take their lipids and proteins for raw material C. Up-regulate synthesis of mRNA and proteins, some of which encode for glucose transporters and enzymes used for glycolysis D. Phagocytose extracellular proteins and lipids and degrade them for energy production E. Macropinocytose metabolites and sugars from the blood for use in glycolysis
C
Streptococcus pneumoniae is a Gram-positive bacterium that colonizes the mucosal surface of the upper respiratory tract in humans. The presence of this bacterium in the nose and throat is widespread in the population, and in most people, colonization with Strep. pneumoniae is asymptomatic. Figure Q2.7 shows a comparison of in vitro growth curves of the wild-type strain of Strep. pneumoniae, as well as a Strep. pneumoniae mutant strain with a defect in one bacterial gene. The graph on the right shows the growth curve following addition of lysozyme during the logarithmic phase of bacterial growth. Which statement could account for the data in these graphs? A. Strain B is wild-type Strep. pneumoniae, and strain A is a mutant that cannot modify its peptidoglycan to be lysozyme-resistant. B. Strain B is wild-type Strep. pneumoniae, and strain A is a mutant that that expresses increased levels of LPS. C. Strain A is wild-type Strep. pneumoniae, and strain B is a mutant that cannot modify its peptidoglycan to be lysozyme-resistant. D. Strain A is wild-type Strep. pneumoniae, and strain B is a mutant that secretes an enzyme that inactivates lysozyme. E. Strain A is wild-type Strep. pneumoniae, and strain B is a mutant that cannot grow well in vitro.
C
The addition and subtraction of nucleotides at the junctions between V, D, and J gene segments creates antibody proteins with wide variations in the numbers of amino acids in their CDR3 regions. This variability in CDR3 length is important as: A. Some antibodies bind relatively flat surfaces and others bind deep clefts in the antigen. B. Overall variability in CDR3 sequence is needed to create a sufficiently diverse antibody repertoire. C. The CDR3 region is more important in binding antigen than the CDR1 and CDR2 regions are. D. Some light chains bind better to heavy chains with longer CDR3 region sequences. E. Longer CDR3 sequences generally create antibodies with higher affinity for the antigen.
C
The best evidence supporting the concept of immunological memory is: A. The increased numbers of antigen receptors expressed by lymphocytes after primary exposure to an antigen B. The increased levels of cytokines made by lymphocytes after primary exposure to an antigen C. The increased rapidity and magnitude of the secondary response to the same antigen D. The increased swelling of lymph nodes during the secondary response to the same antigen E. The long lifespan of vertebrates, which would be impossible without immunological memory
C
The first pattern recognition receptor (PRR) important in innate immune responses was discovered in the fruit fly Drosophila melanogaster. Stimulation of this receptor, called Toll, induces: A. The synthesis of prostaglandins and leukotrienes B. The inflammatory response in Drosophila hemolymph vessels C. The production of antimicrobial peptides D. The recruitment of phagocytic cells to the site of infection E. The activation of Drosophila complement
C
Cytokine receptors of the hematopoietin superfamily engage signaling pathways that begin with JAK kinases and lead to activation of STAT-family transcription factors. Each receptor subunit in this superfamily binds a specific JAK kinase (one of four members) and each receptor complex usually activates one major STAT homodimer (one of seven). The specificity for activation of one STAT homodimer by each cytokine is determined by: A. The specificity of each JAK kinase for only phosphorylating one or two out of the seven possible STAT members B. The specificity of each cytokine receptor complex to only activate one of the four Jak kinase members, which then homodimerizes C. The amino acid sequence surrounding the phosphorylated tyrosine on each cytokine receptor subunit's cytoplasmic tail D. The expression of only one STAT member in each type of immune cell, depending on which cytokine receptors are expressed E. The inhibition of all but one STAT protein by the inhibitor SOCS proteins expressed in each cell type
C. Following cytokine binding, the subunits of the cytokine receptor are induced to dimerize, bringing the associated JAK kinases (one on each subunit, in general) together. These kinases then phosphorylate each other, leading to kinase activation. The activated kinases then phosphorylate tyrosine residues on the cytoplasmic tail of one subunit, usually the subunit that is unique to each cytokine. This phosphorylated sequence on the receptor subunit tail is recognized by a specific STAT protein, which binds to the phosphorylated receptor. This brings the STAT protein into proximity with the activated JAK kinase, leading to STAT protein phosphorylation, dimerization, and migration into the nucleus.
Many different NOD-like receptors, including several with pyrin domains and several with HIN domains, can function to trigger inflammasome assembly leading to the activation of caspase-1. The reason for many different sensors in this innate response system is that: A. Each NOD-like receptor is expressed in a different set of phagocytic cells, depending on its tissue location. B. Each NOD-like receptor resides in a different intracellular compartment. C. Each NOD-like receptor performs a different step in the multi-step cascade leading to inflammasome activation. D. Each NOD-like receptor binds to a different adapter protein and triggers a different form of the inflammasome. E. Each NOD-like receptor recognizes different PAMPs and is activated by different pathogens.
C. IL-1 secretion by dendritic cells requires two signals. One signal is needed to induce the transcription of the IL-1 mRNA by the cells. This signal is often provided by stimulation of a TLR expressed on the dendritic cells. In this example, the S. aureus membrane prep or the live S. aureus bacteria would provide the ligand for TLR stimulation. The second signal needed for IL-1 secretion is the activation of the inflammasome, leading to caspase-1-mediated cleavage of the pro-IL-1 protein. This second signal is provided by the S. aureus toxin or by the live bacteria, which would be producing the toxin. Without both of these signals, no IL-1 is secreted by the dendritic cells.
The first pattern recognition receptor (PRR) important in innate immune responses was discovered in the fruit fly Drosophila melanogaster. Stimulation of this receptor, called Toll, induces: A. The synthesis of prostaglandins and leukotrienes B. The inflammatory response in Drosophila hemolymph vessels C. The production of antimicrobial peptides D. The recruitment of phagocytic cells to the site of infection E. The activation of Drosophila complement
C. In response to activation of Toll by Gram-positive bacteria and some fungi, transcription factors related to mammalian NFκB are activated. This pathway leads to the expression of host defense proteins, including several antimicrobial peptides.
NK cells express receptors from several families, each of which has multiple members. Some of these receptors are activating and others are inhibitory, and NK cell activation is dependent on the balance of signaling overall. The individual NK cells in an individual: A. Always express a majority of activating versus inhibitory receptors B. Are more potent effectors of cytotoxicity than of cytokine-production C. Each express only a subset of all possible NK receptors D. Are not considered members of the innate lymphoid cell lineage E. Undergo massive proliferation in response to infection, similar to T lymphocytes
C. NK receptors belong to several different families, including the killer cell immunoglobulin-like receptor family (KIRs), the killer cell lectin-like receptors (KLRs), and in mice, the Ly49 receptors. Within each family, individual receptors can be activating or inhibitory, and are highly polymorphic between different strains of mice. An important feature of the NK-cell population is that any given NK cell expresses only a subset of the receptors in its potential repertoire, and so not all NK cells in the individual are identical.
The formation of the C3 convertase is a key step in complement activation that occurs in all three complement pathways. This enzyme cleaves C3 in blood plasma, leading to a conformational change in the C3b fragment that exposes its reactive thioester group. The activated C3b is potentially harmful to the host, if it becomes covalently attached to a host cell, rather than to the surface of a pathogen. This deleterious outcome is largely avoided by: A. The inability of active C3b to diffuse away in the blood plasma. B. The inability of active C3b to covalently attach to the membranes of eukaryotic cells. C. The rapid hydrolysis of active C3b in solution, rendering it inactive. D. The tight binding of active C3b to the C3 convertase. E. The ability of active C3b to recruit phagocytic cells.
C. Active C3b is highly labile, and is rapidly inactivated by hydrolysis. This prevents the C3b from remaining active should it diffuse away from the pathogen surface where it was activated by the C3 convertase.
1.30 Multiple choice: Naive B and T lymphocytes are small, quiescent cells with little cytoplasm and low metabolic activity. Yet within hours after being activated following encounter with their antigen, these cells enlarge and up-regulate many biosynthetic and metabolic pathways. Approximately one day later, the cells begin dividing, and for several days they are the most rapidly dividing cells in the body, undergoing 2-4 rounds of cell division every day. In order to maintain this phenomenal rate of cell division, lymphoblasts must: A. Use the large energy stores accumulated by them when they were naive quiescent cells prior to their activation B. Engulf their neighboring small quiescent lymphocytes in order to take their lipids and proteins for raw material C. Up-regulate synthesis of mRNA and proteins, some of which encode for glucose transporters and enzymes used for glycolysis D. Phagocytose extracellular proteins and lipids and degrade them for energy production E. Macropinocytose metabolites and sugars from the blood for use in glycolysis
C. Lymphoblasts up-regulate many biosynthetic and metabolic pathways to produce macromolecules and energy used for rapid cell division. Many of these processes require new mRNA and protein synthesis by the activated lymphocyte. For the purpose of energy production, lymphoblasts up-regulate glucose transporters and enzymes that are used in the glycolytic pathway.
Naive B and T lymphocytes are small, quiescent cells with little cytoplasm and low metabolic activity. Yet within hours after being activated following encounter with their antigen, these cells enlarge and up-regulate many biosynthetic and metabolic pathways. Approximately one day later, the cells begin dividing, and for several days they are the most rapidly dividing cells in the body, undergoing 2-4 rounds of cell division every day. In order to maintain this phenomenal rate of cell division, lymphoblasts must: A. Use the large energy stores accumulated by them when they were naive quiescent cells prior to their activation B. Engulf their neighboring small quiescent lymphocytes in order to take their lipids and proteins for raw material C. Up-regulate synthesis of mRNA and proteins, some of which encode for glucose transporters and enzymes used for glycolysis D. Phagocytose extracellular proteins and lipids and degrade them for energy production E. Macropinocytose metabolites and sugars from the blood for use in glycolysis
C. Lymphoblasts up-regulate many biosynthetic and metabolic pathways to produce macromolecules and energy used for rapid cell division. Many of these processes require new mRNA and protein synthesis by the activated lymphocyte. For the purpose of energy production, lymphoblasts up-regulate glucose transporters and enzymes that are used in the glycolytic pathway.
The skin and bodily secretions provide the first line of defense against infection. One response in this category that is common during upper respiratory virus infections is: A. Production of antibodies B. Infiltration by white blood cells C. Mucus production D. Increased saliva production E. Fever
C. Mucus production is a common response to upper respiratory virus infection. Other responses may also occur, such as fever, production of antibodies, or infiltration of white blood cells, but these are not 'bodily secretions.' Increased saliva is not a symptom common to upper respiratory infections.
Pathogenic infections induce damage to the host by a variety of mechanisms. While many mechanisms are direct effects of the pathogen, some damaging mechanisms result from the immune response to the infection. Examples of damage caused by the host immune response are: A. Exotoxin production --> Endotoxin B. Cell-mediated immunity --> Direct cytopathic effect C. Endotoxin --> Immune complexes D. Direct cytopathic effect --> Endotoxin E. Cell-mediated immunity --> Immune complexes
C. Pathogens cause direct tissue damage by the production of exotoxins or endotoxins, as well as by direct cytopathic effects. Tissue damage caused by the host immune response include damage caused by cell-mediated immunity and by the accumulation of immune complexes.
Even when the complement cascade fails to proceed beyond generating the C3 convertase, complement activation is effective at inducing pathogen uptake and destruction. This process of immune protection is mediated by: A. Activation of complement inhibitory receptors on phagocytes that promote pathogen uptake B. Activation of soluble proteases in the serum that disrupt pathogen membranes C. Engagement of complement receptors on phagocytes by C3b and its cleavage products which promotes phagocytosis D. Engagement of complement receptors on B cells that promotes antibody production E. Stimulation of antimicrobial peptide secretion by phagocytes
C. Phagocytes have a variety of receptors that recognize C3b and fragments of C3b, such as iC3b. Engagement of these complement receptors stimulates phagocytosis of the C3b-coated pathogen, leading to pathogen destruction.
1.24 Multiple choice: Lymph nodes function as meeting points between antigen-bearing dendritic cells arriving from the tissue and recirculating B and T lymphocytes. Whereas the dendritic cells coming from the tissue enter the lymph node via the afferent lymphatic vessels, the recirculating lymphocytes enter the lymph node: A. Also from the lymph fluid draining the tissue B. Directly from their primary lymphoid organ where they develop C. From the blood by crossing the high endothelial venules D. By being trapped in the lymphoid follicle by resident macrophages E. By being carried there by dendritic cells
C. Recirculating lymphocytes are in the blood, and are attracted by chemokines to enter the lymph node. They do this by binding to adhesion molecules and the chemokines posted at high endothelial venules, which are the regions of the blood vessel wall that are in the lymph node. The lymphocytes squeeze themselves through the blood vessel wall to leave the blood and enter the lymph node.
Lymph nodes function as meeting points between antigen-bearing dendritic cells arriving from the tissue and recirculating B and T lymphocytes. Whereas the dendritic cells coming from the tissue enter the lymph node via the afferent lymphatic vessels, the recirculating lymphocytes enter the lymph node: A. Also from the lymph fluid draining the tissue B. Directly from their primary lymphoid organ where they develop C. From the blood by crossing the high endothelial venules D. By being trapped in the lymphoid follicle by resident macrophages E. By being carried there by dendritic cells
C. Recirculating lymphocytes are in the blood, and are attracted by chemokines to enter the lymph node. They do this by binding to adhesion molecules and the chemokines posted at high endothelial venules, which are the regions of the blood vessel wall that are in the lymph node. The lymphocytes squeeze themselves through the blood vessel wall to leave the blood and enter the lymph node.
1.15 Multiple choice: Unlike B lymphocytes, T lymphocytes do not generate a secreted form of their antigen receptor after they are activated and proliferate. This is because the effector functions of T cells are restricted to: A. Responses important in protozoan infections, but not other types of infections B. Interactions with large helminthic parasites, which cannot be phagocytosed C. Interactions with other cells, such as virus-infected cells or other immune cells D. Responses important in mucosal surfaces (e.g., the lung), where antibodies cannot go E. Stimulating B cells and not any other types of cells
C. The effector functions of T cells are all restricted to interactions with other host cells, and not with the pathogen directly. These effector functions include killing of cells infected with intracellular pathogens (cytotoxic T cells), activation of B cells and macrophages (helper T cells), and suppressing the activity of other lymphocytes (regulatory T cells).
Unlike B lymphocytes, T lymphocytes do not generate a secreted form of their antigen receptor after they are activated and proliferate. This is because the effector functions of T cells are restricted to: A. Responses important in protozoan infections, but not other types of infections B. Interactions with large helminthic parasites, which cannot be phagocytosed C. Interactions with other cells, such as virus-infected cells or other immune cells D. Responses important in mucosal surfaces (e.g., the lung), where antibodies cannot go E. Stimulating B cells and not any other types of cells
C. The effector functions of T cells can only interact with other host cells, and not with the pathogen directly. These effector functions include killing of cells infected with intracellular pathogens activation of B cells and macrophages and suppressing the activity of other lymphocytes.
1.28 Multiple choice: The best evidence supporting the concept of immunological memory is: A. The increased numbers of antigen receptors expressed by lymphocytes after primary exposure to an antigen B. The increased levels of cytokines made by lymphocytes after primary exposure to an antigen C. The increased rapidity and magnitude of the secondary response to the same antigen D. The increased swelling of lymph nodes during the secondary response to the same antigen E. The long lifespan of vertebrates, which would be impossible without immunological memory
C. The most compelling evidence supporting the existence of immunological memory is the fact that the secondary response to an antigen is faster, of higher magnitude, and more effective than the response that occurs following an individual's first exposure to that antigen. This is the basis of vaccination.
Multiple choice: While B cells and T cells differ markedly in their functions during an immune response, the two lymphocyte subsets share the enzymatic machinery and overall scheme for generating antigen receptor diversity. This is because: A. B cells and T cells recognize the same form of antigen expressed by an infecting pathogen. B. Animals with B cells developed first, and later evolving species then developed T cells. C. B cells and T cells both need enormous antigen receptor diversity to provide protection against the diversity of pathogens. D. Antibody and T-cell receptor gene segments are both flanked by similar recombination signal sequences. E. B cells and T cells both secrete their antigen receptor proteins after they are activated by antigen-binding.
C. B cells and T cells both need enormous antigen receptor diversity to provide protection against the diversity of pathogens.
The membrane attack complex consists of A.C4b2a B.(C3b)2Bb C.C5b, 6, 7, 8, 9 D.Properdin
C. C5b, 6, 7, 8, 9
Checkpoint blockade' is a therapeutic strategy based on enhancing T cell responses by inhibiting the function of inhibitory receptors, such as CTLA-4, and PD-1. Patients being treated with these protein-based therapeutics would likely be suffering from: A. An autoimmune disease B. An immunodeficiency disease C. Cancer D. Inflammatory bowel disease E. A neurodegenerative disease
C. Cancer
Multiple choice: Three major cell types, dendritic cells, macrophages, and B cells, present peptides bound to MHC class II molecules for recognition by CD4 T cells. In general, these peptides are derived from proteins or pathogens taken up by the cell by endocytosis, phagocytosis, or macropinocytosis. Based on these pathways of antigen uptake, some of the enzymes that degrade proteins to generate peptides for MHC class II presentation are: A. Ubiquitin ligases that tag proteins for degradation by the proteasome B. ATP transporter proteins that deliver endocytic proteins into the cytosol for degradation C. Cysteine proteases like cathepsins that function at acidic pH D. The lysosomal thiol reductase found in the endosomes E. The lysosome-associated membrane trafficking protein, LAMP-2
C. Cysteine proteases like cathepsins that function at acidic pH
Pathogenic infections induce damage to the host by a variety of mechanisms. While many mechanisms are direct effects of the pathogen, some damaging mechanisms result from the immune response to the infection, as illustrated in Figure Q2.2. Examples of damage caused by the host immune response are: A. Exotoxin production : Endotoxin B. Cell-mediated immunity : Direct cytopathic effect C. Endotoxin : Immune Complexes D. Direct cytopathic effect : Endotoxin E. Cell-mediated immunity: Immune complexes
C. Endotoxin : Immune Complexes
Multiple choice: Pathogenic infections induce damage to the host by a variety of mechanisms. While many mechanisms are direct effects of the pathogen, some damaging mechanisms result from the immune response to the infection, as illustrated in Figure Q2.2. Examples of damage caused by the host immune response are: (SEE FIGURE) A. Exotoxin production, Endotoxin B. Cell-mediated immunity, Direct cytopathic effect C. Endotoxin, Immune Complexes D. Direct cytopathic effect, Endotoxin E. Cell-mediated immunity, Immune complexes
C. Endotoxin, Immune Complexes
Even when the complement cascade fails to proceed beyond generating the C3 convertase, complement activation is effective at inducing pathogen uptake and destruction. This process of immune protection is mediated by: A. Activation of complement inhibitory receptors on phagocytes that promote pathogen uptake B. Activation of soluble proteases in the serum that disrupt pathogen membranes C. Engagement of complement receptors on phagocytes by C3b and its cleavage products which promotes phagocytosis D. Engagement of complement receptors on B cells that promotes antibody production E. Stimulation of antimicrobial peptide secretion by phagocytes
C. Engagement of complement receptors on phagocytes by C3b and its cleavage products which promotes phagocytosis
Multiple choice: Even when the complement cascade fails to proceed beyond generating the C3 convertase, complement activation is effective at inducing pathogen uptake and destruction. This process of immune protection is mediated by: A. Activation of complement inhibitory receptors on phagocytes that promote pathogen uptake B. Activation of soluble proteases in the serum that disrupt pathogen membranes C. Engagement of complement receptors on phagocytes by C3b and its cleavage products which promotes phagocytosis D. Engagement of complement receptors on B cells that promotes antibody production E. Stimulation of antimicrobial peptide secretion by phagocytes
C. Engagement of complement receptors on phagocytes by C3b and its cleavage products which promotes phagocytosis
The B cell co-receptor, composed of CD19/CD21/CD81, is a receptor that binds to complement fragments such as C3dg. When an antigen bound by the BCR on a B cell has also been tagged with C3dg, the B cell co-receptor is stimulated together with the BCR. Signaling through the co-receptor: A. Inhibits BCR signaling by leading to ITAM dephosphorylation B. Inhibits BCR signaling by leading to PIP3 dephosphorylation C. Enhances BCR signaling by recruiting and activating PI 3-kinase D. Enhances BCR signaling by bringing the Src-kinase together with Ig- and Ig-. E. Inhibits BCR signaling by sequestering the antigen away from the BCR.
C. Enhances BCR signaling by recruiting and activating PI 3-kinase
Multiple choice: Patients with recurrent infections of Neisseria meningitidis, an extracellular bacterial pathogen that causes meningitis, were examined to determine the underlying cause of their immunodeficiency. A subset of these patients were found to have defects in complement activation on the bacterial surface, a process that for this bacterium is dominated by alternative complement activation leading to C3b deposition on the pathogen surface. When neutrophils from these patients were examined in vitro, the results in Figure Q2.19 were obtained. Based on these data, the identity of the green neutrophil mediator in Figure Q2.19 is likely to be: A. Complement factor B B. The C3 convertase C. Factor P (properdin) D. C3b E. Mannose-binding lectin (MBL)
C. Factor P (properdin)
Patients with recurrent infections of Neisseria meningitidis, an extracellular bacterial pathogen that causes meningitis, were examined to determine the underlying cause of their immunodeficiency. A subset of these patients were found to have defects in complement activation on the bacterial surface, a process that for this bacterium is dominated by alternative complement activation leading to C3b deposition on the pathogen surface. When neutrophils from these patients were examined in vitro, the results in Figure Q2.19 were obtained. Based on these data, the identity of the green neutrophil mediator in Figure Q2.19 is likely to be: A. Complement factor B B. The C3 convertase C. Factor P (properdin) D. C3b E. Mannose-binding lectin (MBL)
C. Factor P (properdin)
Multiple choice: Lymph nodes function as meeting points between antigen-bearing dendritic cells arriving from the tissue and recirculating B and T lymphocytes. Whereas the dendritic cells coming from the tissue enter the lymph node via the afferent lymphatic vessels, the recirculating lymphocytes enter the lymph node: A. Also from the lymph fluid draining the tissue B. Directly from their primary lymphoid organ where they develop C. From the blood by crossing the high endothelial venules D. By being trapped in the lymphoid follicle by resident macrophages E. By being carried there by dendritic cells
C. From the blood by crossing the high endothelial venues
Lymph nodes function as meeting points between antigen-bearing dendritic cells arriving from the tissue and recirculating B and T lymphocytes. Whereas the dendritic cells coming from the tissue enter the lymph node via the afferent lymphatic vessels, the recirculating lymphocytes enter the lymph node: A. Also from the lymph fluid draining the tissue B. Directly from their primary lymphoid organ where they develop C. From the blood by crossing the high endothelial venules D. By being trapped in the lymphoid follicle by resident macrophages E. By being carried there by dendritic cells
C. From the blood by crossing the high endothelial venules
TCR and CD28 signaling together lead to maximal production of IL-2 by the activated T cell. Experiments investigating the mechanism underlying the CD28 co-stimulation-mediated increase in IL-2 production show that T cells stimulated through the TCR plus CD28 have increased levels of IL-2 mRNA compared to cells stimulated through the TCR alone. One important component contributing to increased IL-2 mRNA levels is: A. Increased protein synthesis due to increased production of ribosomes B. Increased glucose metabolism due to increased production of glycolytic enzymes C. Increased mRNA stability after transcription and splicing D. Enhanced mRNA transport from the nucleus to the cytoplasm E. Increased levels of splicing enzymes that increase IL-2 mRNA splicing efficiency
C. Increased mRNA stability after transcription and splicing
Small GTPases, such as Ras, Rho, and cdc42, are activated when they exchange their bound GDP for GTP. In the GTP-bound state, these proteins contribute to signaling by: A. Hydrolyzing the bound GTP back to GDP B. Interacting with GTPase-activating proteins (GAPs) C. Interacting with target proteins and altering their activity D. Diffusing from the membrane and entering the nucleus E. Inducing calcium release from the endoplasmic reticulum
C. Interacting with target proteins and altering their activity
Unlike B lymphocytes, T lymphocytes do not generate a secreted form of their antigen receptor after they are activated and proliferate. This is because the effector functions of T cells are restricted to: A. Responses important in protozoan infections, but not other types of infections B. Interactions with large helminthic parasites, which cannot be phagocytosed C. Interactions with other cells, such as virus-infected cells or other immune cells D. Responses important in mucosal surfaces (e.g., the lung), where antibodies cannot go E. Stimulating B cells and not any other types of cells
C. Interactions with other cells, such as virus-infected cells or other immune cells
Multiple choice: The mechanism of cross-presentation by dendritic cells is an essential pathway for generating CD8 T cell responses to some intracellular pathogens. If this pathway did not exist, we would be highly susceptible to: A. Intracellular pathogens that can survive inside macrophage endocytic vesicles B. Intracellular pathogens that are able to evade antibody responses C. Intracellular pathogens that do not infect and replicate in dendritic cells D. Intracellular pathogens that can spread from cell to cell by inducing cell fusion E. Intracellular pathogens that infect and replicate in red blood cells
C. Intracellular pathogens that do not infect and replicate in dendritic cells
The integrin LFA-1 is constitutively expressed on the surface of resting T cells. Yet, integrin-dependent T cell adhesion to antigen-presenting cells increases substantially following TCR stimulation. This increased integrin-dependent adhesion is mediated in part by: A. Increased synthesis of the LFA-1 protein B. Increased transport of intracellular pools of LFA-1 to the cell surface C. LFA-1 conversion to a high affinity binding state D. Increased phosphorylation of the LFA-1 cytoplasmic tail E. Activation of cdc42 and WASp
C. LFA-1 conversion to a high affinity binding state
Multiple choice: NKG2D is an activating receptor expressed on NK cells, gamma:delta T cells, and some cytotoxic alpha:beta T cells. When stressed or infected cells up-regulate receptors that bind to and activate NKG2D molecules, the stressed or infected cells will be killed. This pathway relies on the fact that stressed or infected cells up-regulate: A. All classical MHC class I molecules B. HLA-C molecules that bind KIRs C. MHC class Ib genes such as MICA, MICB, and RAET1 D. Qa-1 and HLA-E molecules that bind leader peptides of other HLA class I molecules E. HLA-G molecules just like those expressed on the fetal-derived cells in the placenta
C. MHC class Ib genes such as MICA, MICB, and RAET1
Multiple choice: The virus shown in the diagram below is only able to infect and replicate in epithelial cells. In order for the cross-presenting dendritic cell to display viral peptides, rather than self peptides on its surface MHC class I proteins, which of the following procedures could be utilized, starting with the components shown in Figure Q6.8? (SEE IMAGE) A. Mix epithelial cells with heat-killed virus, wait 24 hrs, wash away any virus particles outside the epithelial cells, then add epithelial cells to dendritic cells. B. Mix epithelial cells with viral peptides, wait 24 hrs, wash away any viral peptides not bound to the epithelial cells, then add epithelial cells to dendritic cells. C. Mix epithelial cells with live virus particles, wait 24 hrs, wash away any virus particles outside the epithelial cells, then add epithelial cells to dendritic cells. D. Mix dendritic cells with viral nucleic acids and epithelial cells for 24 hrs. E. MIx epithelial cells will viral nucleic acids, wait 24 hrs, wash away any viral nucleic acid remaining outside the epithelial cells, then add epithelial cells to dendritic cells.
C. Mix epithelial cells with live virus particles, wait 24 hrs, wash away any virus particles outside the epithelial cells, then add epithelial cells to dendritic cells.
Multiple choice: The extensive polymorphism of MHC genes in the population is thought to represent an evolutionary response to outflank the evasive strategies of pathogens. This polymorphism makes it difficult for pathogens to eliminate all potential MHC binding epitopes from their proteins. Based on this reasoning, it would seem advantageous for each individual to encode more than three different MHC class I and three different MHC class II genes per chromosome copy. If some individuals in the population had MHC loci that encoded 10 different MHC class I and 10 different MHC class II genes, the T cell repertoire in those individuals would likely be: A. Much more diverse than in the rest of the individuals of that population B. Much better at recognizing rare pathogens not encountered by most individuals in that population C. Much less diverse than the rest of the individuals in that population D. Much more alloreactive than the T cells found in the other individuals of that population E. Very reactive to bacterial and viral superantigens
C. Much less diverse than the rest of the individuals in that population
The skin and bodily secretions provide the first line of defense against infection. One response in this category that is common during upper respiratory virus infections is: A. Production of antibodies B. Infiltration by white blood cells C. Mucus production D. Increased saliva production E. Fever
C. Mucus production
T cells with defective TCR signaling are discovered, and found to have an inactivating mutation in a key TCR signaling protein. Using an antibody that recognizes the phosphorylated (activated) form of the Erk Map-kinase, stimulated T cells are permeabilized, stained with this antibody, and analyzed on the flow cytometer. These data are shown in Figure Q7.21. Additional experiments examining Ca2+ influx into T cells following TCR stimulation show a normal response in the mutant T cells. One likely candidate gene that could be mutated in the defective cells is: A. PLC- B. ITK C. RasGRP D. Calcineurin E. WASp
C. RasGRP
Figure Q5.5 shows the germ-line configuration of three V gene segments (#1, 2, 3), and two J gene segments (#4, 5). Which of the choices below represents a DNA configuration that would result from V-to-J recombination? (SEE IMAGE)
C. SEE IMAGE
Multiple choice: Both MHC class I and MHC class II molecules are highly polymorphic genes in the human population, with tens to hundreds of different alleles co-existing in the population. This means that a comparison of the MHC protein sequences between two individuals would reveal amino acid differences between one individual and the next. However, these amino acid differences are not randomly distributed along the entire protein, but are clustered in certain locations. The diagram in Figure Q4.16 that most correctly indicates the regions of greatest variability between different MHC proteins (shown by the red highlights) is: (SEE IMAGE)
C. SEE IMAGE
The drawing in Figure Q4.12 shows antibodies bound to repetitive epitopes on the surface of a bacterial pathogen. Even though all of these epitopes are identical, not all of them have antibodies bound to them. The most likely explanation for this failure of antibodies to bind to every possible epitope on the surface of the pathogen is: A. There is an insufficient amount of antibody to saturate all the epitopes. B. The pathogen has an immune evasion strategy to avoid antibody binding to all epitopes. C. Some of the epitopes cannot bind antibody due to steric hindrance. D. The antibodies are only able to bind when both antigen-binding sites are engaged on the pathogen surface. E. The epitopes on the pathogen are not all in the same conformation, so not all will bind the same antibody.
C. Some of the epitopes cannot bind antibody due to steric hindrance
Multiple choice: The drawing in Figure Q4.12 shows antibodies bound to repetitive epitopes on the surface of a bacterial pathogen. Even though all of these epitopes are identical, not all of them have antibodies bound to them. (SEE IMAGE) The most likely explanation for this failure of antibodies to bind to every possible epitope on the surface of the pathogen is: A. There is an insufficient amount of antibody to saturate all the epitopes. B. The pathogen has an immune evasion strategy to avoid antibody binding to all epitopes. C. Some of the epitopes cannot bind antibody due to steric hindrance. D. The antibodies are only able to bind when both antigen-binding sites are engaged on the pathogen surface. E. The epitopes on the pathogen are not all in the same conformation, so not all will bind the same antibody.
C. Some of the epitopes cannot bind antibody due to steric hindrance.
Multiple choice: MHC polymorphism at individual MHC genes appears to have been strongly selected by evolutionary pressures. In other words, there appears to be selection for maintaining hundreds to thousands of different alleles of each MHC gene in the population. This notion is based on the observation that nucleotide differences between alleles that lead to amino acid substitutions are more frequent than those that are silent substitutions (i.e., not changing the amino acid sequence of the protein). In addition, the positions within the MHC protein where most of the allelic sequence variation occurs are not randomly distributed, but are concentrated in certain regions of the MHC protein. This latter point indicates: A. That some nucleotide sequences within the MHC genes are hot-spots for mutation B. That MHC genes are more susceptible to point mutations than to larger nucleotide deletions C. That MHC allelic polymorphism has been driven by selection for diversity in peptide binding specificity D. That MHC genes are more susceptible to all types of mutations than are other genes in the genome E. That MHC polymorphism has evolved to prevent pathogens that infect non- human primates from infecting humans
C. That MHC allelic polymorphism has been driven by selection for diversity in peptide binding specificity
The antibody surface involved in antigen binding varies depending on the size and nature of the antigen. This surface can be concave or flat, and sometimes, can have extended protrusions. This is accomplished by: A. Flexibility in the hinge regions of the antibody allowing rotation of the antigen-binding sites B. Some antibodies using V region framework sequences instead of the CDRs to bind antigen C. The ability of different CDR sequences to form many structurally distinct shapes and surfaces D. The ability of the same heavy chain to pair with different light chains E. The differential usage of κ versus λ light chains, as κ chains form concave binding sites whereas λ chains make flatter surfaces
C. The ability of different CDR sequences to form many structurally distinct shapes and surfaces
Multiple choice: Cytokine receptors of the hematopoietin superfamily engage signaling pathways that begin with JAK kinases and lead to activation of STAT-family transcription factors. Each receptor subunit in this superfamily binds a specific JAK kinase (one of four members) and each receptor complex usually activates one major STAT homodimer (one of seven). The specificity for activation of one STAT homodimer by each cytokine is determined by: A. The specificity of each JAK kinase for only phosphorylating one or two out of the seven possible STAT members B. The specificity of each cytokine receptor complex to only activate one of the four Jak kinase members, which then homodimerizes C. The amino acid sequence surrounding the phosphorylated tyrosine on each cytokine receptor subunit's cytoplasmic tail D. The expression of only one STAT member in each type of immune cell, depending on which cytokine receptors are expressed E. The inhibition of all but one STAT protein by the inhibitor SOCS proteins expressed in each cell type
C. The amino acid sequence surrounding the phosphorylated tyrosine on each cytokine receptor subunit's cytoplasmic tail
Multiple choice: A mutagenesis screen performed on mice identified a gene with an important function in B cells. Analysis of B cells from the spleens of these mutant mice showed the results shown in Figure Q5.23A. However, when the C coding sequences were determined, no mutations in these DNA sequences were found. To study this further, genetic crosses were set-up with another mouse strain carrying an allelic variant of the immunoglobulin heavy chain locus. The original mutant mouse strain (strain A) carries IgMa and IgDa alleles of these heavy chain genes. The second mouse strain (strain B) carries the IgMb and IgDb alleles of the heavy chain genes. These two parental strains were crossed together, generating progeny that were all heterozygous for IgM and IgD alleles (i.e., all progeny are IgMa/b and IgDa/b). These heterozygous progeny represent the F1 generation. Brother/sister matings of F1 mice generate F2 progeny. These F2 mice were genotyped by PCR analysis using primers that allow discrimination of the two alleles of the heavy chain locus. As expected 50% of the F2 mice were heterozygous for IgMa/IgDa and IgMb/IgDb, 25% were homozygous for IgMa/IgDa, and the final 25% homozygous for IgMb/IgDb. Further analysis was performed on the F2 progeny mice homozygous for either IgMa/IgDa or for IgMb/IgDb. The B cells from these mice were stained with antibodies to IgM and IgD, and the results shown in Figure Q5.23B were obtained. (SEE IMAGE) Based on these data, the mutation in the original mutant mouse strain most likely inactivates: A. The gene for a transcription factor required for IgD gene transcription B. A regulatory region in the immunoglobulin heavy chain gene locus required for IgD gene transcription C. The gene for a factor required for alternative mRNA splicing of the immunoglobulin heavy chain primary mRNA transcript D. The gene encoding the RAG-1 or RAG-2 recombinase E. The gene for a factor that is required for IgD surface expression
C. The gene for a factor required for alternative mRNA splicing of the immunoglobulin heavy chain primary mRNA transcript
Multiple choice: The best evidence supporting the concept of immunological memory is: A. The increased numbers of antigen receptors expressed by lymphocytes after primary exposure to an antigen B. The increased levels of cytokines made by lymphocytes after primary exposure to an antigen C. The increased rapidity and magnitude of the secondary response to the same antigen D. The increased swelling of lymph nodes during the secondary response to the same antigen E. The long lifespan of vertebrates, which would be impossible without immunological memory
C. The increased rapidity and magnitude of the secondary response to the same antigen
The best evidence supporting the concept of immunological memory is: A. The increased numbers of antigen receptors expressed by lymphocytes after primary exposure to an antigen B. The increased levels of cytokines made by lymphocytes after primary exposure to an antigen C. The increased rapidity and magnitude of the secondary response to the same antigen D. The increased swelling of lymph nodes during the secondary response to the same antigen E. The long lifespan of vertebrates, which would be impossible without immunological memory
C. The increased rapidity and magnitude of the secondary response to the same antigen
Multiple choice: Dendritic cells in the skin, known as Langerhans cells, express very high levels of the NOD-like receptor, NLRP3. Previous studies showed that treatment of these cells with the Staphylococcus aureus pore-forming toxin causes K+ efflux from the cells. To investigate whether this signal could induce IL-1 (an inflammatory cytokine) secretion by the cells, the following study (Figure Q3.16) was performed: The explanation for these results is: A. NLRP3 is not activated by K+ efflux from the cells. B. The S. aureus toxin does not kill the Langerhans cells. C. The live S. aureus bacteria activate a TLR and NLRP3. D. The S. aureus membrane prep does not contain a TLR ligand. E. TLR activation by S. aureus membranes induces interferon production.
C. The live S. aureus bacteria activate a TLR and NLRP3.
Multiple choice: For immunoglobulin heavy and light chain genes, and for T-cell receptor beta chain genes, there are a large number of V gene segments, and relatively few J and/or D segments that rearrange to form the final coding sequence for each gene. The TCR alpha locus is different in this regard, and this difference is thought to reflect the fact that nearly all alpha:beta T-cell receptors recognize a peptide bound to an MHC molecule. This unique feature of the T-cell receptor locus is: A. The presence of only five different V-alpha gene segments B. The presence of two different C-alpha coding sequences C. The presence of over sixty different J-alpha gene segments D. The absence of D gene segments E. The large sequence distance separating the V-alpha gene segments from the J-alpha gene segments
C. The presence of over sixty different J-alpha gene segments
Multiple choice: The formation of the C3 convertase is a key step in complement activation that occurs in all three complement pathways. This enzyme cleaves C3 in blood plasma, leading to a conformational change in the C3b fragment that exposes its reactive thioester group. The activated C3b is potentially harmful to the host, if it becomes covalently attached to a host cell, rather than to the surface of a pathogen. This deleterious outcome is largely avoided by: A. The inability of active C3b to diffuse away in the blood plasma. B. The inability of active C3b to covalently attach to the membranes of eukaryotic cells. C. The rapid hydrolysis of active C3b in solution, rendering it inactive. D. The tight binding of active C3b to the C3 convertase. E. The ability of active C3b to recruit phagocytic cells.
C. The rapid hydrolysis of active C3b in solution, rendering it inactive.
The formation of the C3 convertase is a key step in complement activation that occurs in all three complement pathways. This enzyme cleaves C3 in blood plasma, leading to a conformational change in the C3b fragment that exposes its reactive thioester group. The activated C3b is potentially harmful to the host, if it becomes covalently attached to a host cell, rather than to the surface of a pathogen. This deleterious outcome is largely avoided by: A. The inability of active C3b to diffuse away in the blood plasma. B. The inability of active C3b to covalently attach to the membranes of eukaryotic cells. C. The rapid hydrolysis of active C3b in solution, rendering it inactive. D. The tight binding of active C3b to the C3 convertase. E. The ability of active C3b to recruit phagocytic cells.
C. The rapid hydrolysis of active C3b in solution, rendering it inactive.
The TCR and BCR are multi-subunit receptor complexes. Experiments examining the synthesis and transport of these receptors to the lymphocyte cell surface have shown that the signaling subunits of each receptor complex are required for transport of the ligand-binding receptor subunits to the cell surface. One possible reason for this stringent control on cell surface expression is: A. To ensure that very few complete TCRs or BCRs are expressed on the lymphocyte surface B. To ensure that each lymphocyte expresses only a single specificity of antigen receptor C. To prevent surface expression of receptors that will bind ligand but fail to induce signals D. To prevent lymphocytes from triggering antigen receptor signaling pathways from intracellular forms of the receptors E. To ensure that equimolar amounts of all antigen receptor signaling subunits are produced
C. To prevent surface expression of receptors that will bind ligand but fail to induce signals
Multiple choice: Naive B and T lymphocytes are small, quiescent cells with little cytoplasm and low metabolic activity. Yet within hours after being activated following encounter with their antigen, these cells enlarge and up-regulate many biosynthetic and metabolic pathways. Approximately one day later, the cells begin dividing, and for several days they are the most rapidly dividing cells in the body, undergoing 2-4 rounds of cell division every day. In order to maintain this phenomenal rate of cell division, lymphoblasts must: A. Use the large energy stores accumulated by them when they were naive quiescent cells prior to their activation B. Engulf their neighboring small quiescent lymphocytes in order to take their lipids and proteins for raw material C. Up-regulate synthesis of mRNA and proteins, some of which encode for glucose transporters and enzymes used for glycolysis D. Phagocytose extracellular proteins and lipids and degrade them for energy production E. Macropinocytose metabolites and sugars from the blood for use in glycolysis
C. Up-regulate synthesis of mRNA and proteins, some of which encode for glucose transporters and enzymes used for glycolysis
Naive B and T lymphocytes are small, quiescent cells with little cytoplasm and low metabolic activity. Yet within hours after being activated following encounter with their antigen, these cells enlarge and up-regulate many biosynthetic and metabolic pathways. Approximately one day later, the cells begin dividing, and for several days they are the most rapidly dividing cells in the body, undergoing 2-4 rounds of cell division every day. In order to maintain this phenomenal rate of cell division, lymphoblasts must: A. Use the large energy stores accumulated by them when they were naive quiescent cells prior to their activation B. Engulf their neighboring small quiescent lymphocytes in order to take their lipids and proteins for raw material C. Up-regulate synthesis of mRNA and proteins, some of which encode for glucose transporters and enzymes used for glycolysis D. Phagocytose extracellular proteins and lipids and degrade them for energy production E. Macropinocytose metabolites and sugars from the blood for use in glycolysis
C. Up-regulate synthesis of mRNA and proteins, some of which encode for glucose transporters and enzymes used for glycolysis
Multiple choice: As a family, TLRs can recognize PAMPs associated with a broad array of different pathogens, including bacteria, viruses, and fungi. Patients with a specific susceptibility to herpesvirus infections have a defect in their ability to respond to viral nucleic acids using TLR-3, TLR-7, or TLR-9, even though these proteins are expressed in the patients' cells. Analysis of the TLRs in macrophages and dendritic cells from these patients would likely show which of the arrangements in Figure Q3.11? (LOOK AT FIGURE)
C. all on outside of ring
Streptococcus pneumoniae is a Gram-positive bacterium that colonizes the mucosal surface of the upper respiratory tract in humans. The presence of this bacterium in the nose and throat is widespread in the population, and in most people, colonization with Strep. pneumoniae is asymptomatic. Figure Q2.7 shows a comparison of in vitro growth curves of the wild-type strain of Strep. pneumoniae, as well as a Strep. pneumoniae mutant strain with a defect in one bacterial gene. The graph on the right shows the growth curve following addition of lysozyme during the logarithmic phase of bacterial growth. Which statement could account for the data in these graphs? A. Strain B is wild-type Strep. pneumoniae, and strain A is a mutant that cannot modify its peptidoglycan to be lysozyme-resistant. B. Strain B is wild-type Strep. pneumoniae, and strain A is a mutant that that expresses increased levels of LPS. C. Strain A is wild-type Strep. pneumoniae, and strain B is a mutant that cannot modify its peptidoglycan to be lysozyme-resistant. D. Strain A is wild-type Strep. pneumoniae, and strain B is a mutant that secretes an enzyme that inactivates lysozyme. E. Strain A is wild-type Strep. pneumoniae, and strain B is a mutant that cannot grow well in vitro.
C.Strain A is wild-type Strep. pneumoniae, and strain B is a mutant that cannot modify its peptidoglycan to be lysozyme-resistant.
What is C1 composed of?
C1 complex is composed of a large subunit (C1q), which acts as the pathogen sensor, and (C1r and C1s), which are initially in their inactive form C1r and C1s are closely related to MASP-2
Which components of complement could be missing and still leave the complement system capable of activation by the alternative pathway
C1, C2, and C4
Mannose-binding lectin (MBL) is most similar to:
C1q
Which one of the following is NEITHER a C3 convertase NOR a C5 convertase?
C1q, C1r and C1s
When does C2 become susceptible to cleavage by C1s?
C2 becomes susceptible to cleavage by C1s only when it is bound by C4b.
This complement component can be cleaved by a complex it might be part of:
C3
what do C3a and C5a do when they are cleaved and released?
C3a and C5a act as chemoattractants that recruit immune-system cells to the site of infection and cause inflammation (bottom left).
During opsonization what is deposited on the surface of the pathogen?
C3b (or C4b)
What does C3b bind to?
C3b binds covalently to adjacent molecules on the pathogen surface. Otherwise it is inactivated by hydrolysis.
What happens once C3b binds to pathogen?
C3b bound to a pathogen acts as an opsonin, enabling phagocytes that express receptors for C3b to ingest the complement-coated microbe more easily (bottom center).
What happens when C3b when it binds to C3 CONVERTASE?
C3b can also bind to the C3 convertases produced by the classical and lectin pathways and form another multisubunit enzyme, the C5 convertase.
once C3 CONVERTASE cleaves C3 , what happens to C3b and C3a?
C3b is left bound to pathogen , while C3a is released and does not bind to pathogen. C3b that is not covalently coupled to a surface is rapidly inactivated by hydrolysis.
Complement component C3 is cleaved by
C3bBB
What does C5 CONVERTASE do?
C5 convertase cleaves C5, liberating the highly inflammatory peptide C5a and generating C5b. C5b initiates the 'late' events of complement activation, in which additional complement proteins interact with C5b to form a membrane- attack complex (MAC) on the pathogen surface, creating a pore in the cell membrane that leads to cell lysis (see Fig. 2.15, bottom right).
How is C5 CONVERTASE formed in both the CLASSICAL AND LECTIN PATHWAYS?
C5 convertase is formed by the binding of C3b to C4b2a to make C4b2a3b.
Local inflammation during complement activation is caused by cytokine fragments:
C5a and C3a
The membrane attack complex (MAC) consists of
C5b, 6, 7, 8, 9
Complement activation leads to -production of cytokines: fragment [cc]and C3a lead to local inflammation -opsonization: [dd ]is deposited to the surface of the pathogen -formation of the [ee]: pore formation in the membrane of the pathogen
CC. C5a dd. C3b ee. MAC
Promote naive T-cell entry into lymph nodes
CCL19/21
Effector memory T-cells (TEMs) can be distinguished from the central memory T-cells (TCMs) by:
CCR7 expression
Gut-homing activated T cells express the following chemokine receptor and adhesion molecule combination:
CCR9: a4:B7 integrin
Gut-homing activated T cells express the following chemokine receptor and adhesion molecule combination:
CCR9; α4:β7 integrin
At least some NK-T cells (NKTs) express ________
CD4
Individuals with the HIV-induced immunodeficiency disease AIDS have a progressive loss in the number of CD4 T cells in their bodies. These patients have a greatly increased rate of life-threatening disease caused by the inability of their immune system to control infections of the intracellular bacterium, Mycobacterium tuberculosis (Mtb). Mtb infects macrophages and then replicates in the cell's phagosomes. The most important immune mechanism lacking in these patients that leads to their increased susceptibility to Mtb is a defect in:
CD4 T cell help for cytotoxic effector CD8 T cells
The cellular distribution of MHC class I versus MHC class II molecules is quite different, with MHC class II molecules generally expressed on a very limited set of cell types. This is because:
CD4 T cells generally secrete cytokines that act on macrophages and B cells.
Match the following molecules on antigen-presenting cells to their binding partners on T cells: CD40
CD40L
Which one of the TNF superfamily ligand does NOT elicit apoptosis?
CD40L
Antigen receptor signaling pathways are regulated by a balanced equilibrium between tyrosine kinases and tyrosine phosphatases. In general, activation of signaling proceeds when the kinase activities leading to auto-phosphorylation of Lck, to phosphorylation of ZAP-70, and to phosphorylation of downstream adapters and scaffolds exceeds the activity of phosphatases acting on these substrates. Therefore, it came as a surprise when T cells lacking the membrane tyrosine phosphatase, CD45, were first generated, and were found to be unable to be activated by TCR stimulation. Name one important function of CD45 in T cells that explains the requirement for this phosphatase in TCR signaling.
CD45 acts as the phosphatase that de-phosphorylates the C-terminal negative regulatory tyrosine of Lck. When this tyrosine is phosphorylated and binds to the Lck SH2 domain, Lck is held in an inactive conformation. So TCR signaling initiated by Lck cannot occur without CD45 to dephosphorylate this site.
Which of the surface proteins is neither a receptor nor coreceptor for HIV?
CD8
T cells expressing the co-receptor CD8 are generally cytotoxic cells, with an important function in eliminating virus infections that can occur in many different cell types and tissues. In contrast, CD4 T cells directly interact with a very restricted set of cells, such as dendritic cells, macrophages, and B cells. Describe one important mechanism that accounts for this division of labor between CD8 and CD4 T cells.
CD8 T cells recognize antigenic peptides bound to MHC I molecules, which are expressed on nearly all cells of the body. Therefore, any cell type that becomes virus-infected would be able to present viral peptides on MHC I molecules for recognition by CD8 T cells. In contrast, CD4 T cells recognize antigenic peptides bound to MHC II molecules. MHC II proteins are expressed only on other cells of the immune system, such as dendritic cells, macrophages, and B cells. Due to the restricted expression of MHC class II proteins, CD4 T cells are restricted to interacting with these cells of the immune system.
T cells expressing the co-receptor CD8 are generally cytotoxic cells, with an important function in eliminating virus infections that can occur in many different cell types and tissues. In contrast, CD4 T cells directly interact with a very restricted set of cells, such as dendritic cells, macrophages, and B cells. Describe one important mechanism that accounts for this division of labor between CD8 and CD4 T cells.
CD8 T cells recognize antigenic peptides bound to MHC class I molecules expressed on almost all cells of the body. So, any cell type that's virus-infected would be able to present viral peptides on MHC class I molecules for recognition by CD8 T cells. CD4 T cells recognize antigenic peptides bound to MHC class II molecules. MHC class II proteins are expressed only on other immune cells, like dendritic cells, macrophages, and B cells. Due to restricted expression of MHC class II proteins, CD4 T cells are restricted to interacting with immune system cells.
1.35 Short answer: T cells expressing the co-receptor CD8 are generally cytotoxic cells, with an important function in eliminating virus infections that can occur in many different cell types and tissues. In contrast, CD4 T cells directly interact with a very restricted set of cells, such as dendritic cells, macrophages, and B cells. Describe one important mechanism that accounts for this division of labor between CD8 and CD4 T cells.
CD8 T cells recognize antigenic peptides bound to MHC class I molecules, which are expressed on nearly all cells of the body. Therefore, any cell type that becomes virus-infected would be able to present viral peptides on MHC class I molecules for recognition by CD8 T cells. In contrast, CD4 T cells recognize antigenic peptides bound to MHC class II molecules. MHC class II proteins are expressed only on other cells of the immune system, such as dendritic cells, macrophages, and B cells. Due to the restricted expression of MHC class II proteins, CD4 T cells are restricted to interacting with these cells of the immune system.
Fill in the blank in each statement below with the most appropriate terms: protein kinase(s); CD28; CD8; CD4; CD45; B7; class I MHC; IL-6. Knockout mice lacking class I MHC molecules fail to produce thymocytes bearing _______ T cells bearing _______ are absent from the lymph nodes of knockout mice lacking class II MHC molecules.
CD8; CD4
Which statement is correct regarding the role of co-stimulatory/co-inhibitory interactions during T cell activation
CTLA-4 expression provides inhibitory signal during the T cell activation because CTLA-4 has a stronger affinity than CD28 for CD80/86
Cell-mediated effector cells include
CTLs, NK-T cells, and NK cells
B cells follow which of the following chemotactic signals to migrate to the cortical regions of secondary lymphoid tissue?
CXCL13
Which of the following is a co-receptor for HIV?
CXCR4
Which of the following antigen types could be characterized as TI antigens?
Capsular polysaccharides Bacterial cell wall components
Immune response against gluten in food, activated CD4 T cells secrete IFNy, leading to intestinal inflammation
Celiac disease
Pathogenic infections induce damage to the hose by a variety of mechanisms. While many mechanisms are direct effects of the pathogen, some damaging mechanisms result from the immune caused by the host immune responses are:
Cell-mediated immunity; immune complexes
How are β-Defensins (and some α-defensins) produced lungs?
Center panel: Type II pneumocytes in the lung alveoli (not shown) also produce and secrete antimicrobial defensins. In the lung, the airways are lined by ciliated epithelium. Beating of the cilia moves a continuous stream of mucus (green) secreted by goblet cells outward, trapping and ejecting potential pathogens.
Many of the inflammatory mediators produced by tissue macrophages at sites of infection act on the endothelial cells lining the blood vessel walls. An exception to this is (are) the:
Chemokines that induce directed migration of blood monocytes
What happens when the C3 COMPLEMENT PROTEIN is cleaved?
Cleavage of C3 produces a small protein fragment called C3a and the remaining larger fragment, C3b. The larger fragment for other factors is designated by the suffix b, with one exception. For C2, the larger fragment was named C2a by its discoverers,
The adaptive immune system developed a strategy for monitoring the proteins synthesized in virtually any cell in the body, thereby preventing pathogens from 'hiding out' by adopting an intracellular lifestyle. To accomplish this, the immune system:
Co-opted the ubiquitin-proteasome system used by cell for protein turnover
alpha:beta TCRs generally have a binding preference for either peptide:MHC class I or peptide:MHC class II complexes. However, on occasion, one alpha:beta TCR might actually be able to recognize either class of peptide:MHC complexes. When such an alpha:beta TCR is expressed on a CD4 T cell, it will only activate its T cell after binding to peptide:MHC class II complexes. Why is this the case?
Co-receptors (CD4 or CD8) expressed on each T cell have an important function in alpha:beta TCR recognition leading to T cell activation. Experiments demonstrate the CD4 molecule and T-cell receptor can bind simultaneously to the same peptide:MHC class II complex. CD4 then enhances sensitivity to antigen. T cells are roughly 100x more sensitive to the antigen when CD4 is present. The enhancement process results from the intracellular part of CD4 binding to Lck, a cytoplasmic tyrosine kinase. This brings Lck close to the T-cell receptor complex and helps activate the signaling cascade induced by antigen recognition. An analogous situation occurs for CD8 T cells and their recognition of peptide:MHC class I complexes.
Which of the following statement is NOT correct about supramolecular activation complex (SMAC), also known as immunological synapse?
Co-receptors such as CD4 or CD8 are mostly found in peripheral SMAC
Which cell type is found in both B- and T-cell lineages?
Common lymphoid progenitors
When a pathogen breaches the host's epithelial barriers and initial antimicrobial defenses, it next encounters a major component of innate immunity, __________ is/are a collection of soluble proteins present in blood and other body fluids that can eliminate pathogens through lysis and opsonization.
Complement
What is the COMPLEMENT SYSTEM/COMPLEMENT?
Complement is a collection of soluble proteins present in blood and other body fluids. COMPLEMENT originally evolved as part of the innate immune system and that it still provides protection early in infection, in the absence of antibodies, through more ancient pathways of complement activation.
Anatomic barriers are fixed defenses against infection and consist of the epithelia that line the internal and external surfaces of the body along with the phagocytes residing beneath all epithelial surfaces. Which of the following is an example of a mode of transmission where the pathogen route of entry is through the gastrointestinal tract?
Contaminated water or food
The integrin LFA-1 is constitutively expressed on the surface of resting T cells. Yet, integrin-dependent T cell adhesion to antigen-presenting cells increases substantially following TCR stimulation. This increased integrin-dependent adhesion is mediated in part by:
Conversion of LFA-1 to a high affinity binding state
Inhibition of calcineurin activity, NFAT activation, and IL-2 production
Cyclosporin A
Clycosporin A and rapamycin are each used as T cell immunosuppressants. ... As a consequence,
Cyclosporin A, but not rapamycin, blocks cytokine production by T cells
Antigen-presenting cells present peptides bound to MHC class II molecules for recognition by CD4 T cells. In general, these peptides are derived from proteins or pathogens taken up by the cell by endocytosis, phagocytosis, or macropinocytosis. The enzymes that degrade these proteins to generate peptides for MHC class II presentation are:
Cysteine proteases like cathepsins that function at acidic pH
Collectively, which proteins induce a state of inflammation in the tissue, attract monocytes and neutrophils to the infection, and allow plasma proteins to enter the tissue from the blood?
Cytokines and chemokines
Innate lymphoid cells (ILCs) are effector cells that generally reside in barrier tissues, such as the skin, the gut, and the lung. These cells closely resemble subsets of T lymphocytes, but lack a T cell antigen-receptor. Instead, these cells produce their effector molecules following stimulation by:
Cytokines made by other innate cells, such as macrophages or dendritic cells
An infant with recurrent bacterial and fungal infections is suspected to have an immunodeficiency disease. Within two days after exposure to a pathogen, the organisms have proliferated to dangerous levels requiring immediate systemic antibiotic treatment. It is unlikely that this infant has a defect in B or T lymphocyte responses to the infection because: A. Bacteria and fungi do not require B cell or T cell responses for their clearance. B. Bacteria and fungi are not efficiently transported to draining lymph nodes to initiate adaptive immune responses. C. Systemic infections of bacteria and fungi are usually cleared by the spleen. D. The defective immune response occurs too rapidly following infection to be due to a defect in B or T lymphocytes responses. E. Adaptive immune responses require dendritic cells to take up and degrade pathogens.
D
Immunodeficiency diseases occur when individuals have defects in leukocyte adhesion to inflamed endothelial cells, thereby impeding the extravasation of phagocytes into infected tissues. When neutrophils from one class of these patients were isolated and tested using in vitro assays for neutrophil-endothelial cell interactions and extravasation, it was found that the neutrophils could slowly roll along the endothelial vessel wall but were unable to arrest and migrate across the endothelium. The most likely protein deficient in these neutrophils is: A. ICAM-1 or ICAM-2 B. P-selectin C. E-selectin D. An integrin E. Sulfated sialyl-Lewis X
D
In patients with lymphomas, the cancer cells invade the bone marrow and destroy the environment required for normal hematopoiesis. This leads to bone marrow failure, which disrupts the production of hematopoietic cell lineages. All of the following cell types would be affected by this EXCEPT: A. Red blood cells B. Macrophages C. Lymphocytes D. Endothelial cells E. Granulocytes
D
In recent years, several new vaccines have been developed that are made from purified viral surface proteins, rather than intact or live viruses. They are referred to as subunit vaccines. In order to generate a protective adaptive immune response to a subunit vaccine, the viral protein(s) must be mixed with an adjuvant. The adjuvant functions to: A. Mimic the process of normal virus entry by binding to the host receptor and inducing receptor-mediated endocytosis B. Induce vascular permeability to promote the accumulation of fluid and serum proteins at the vaccine injection site C. Induce the production of chemotactic proteins that recruit neutrophils and then monocytes to the site of vaccine injection D. Stimulate dendritic cells to up-regulate co-stimulatory molecules and migrate to the regional lymph node E. Promote the activation of the complement cascade to induce complement deposition on the viral subunit proteins
D
Innate lymphoid cells (ILCs) are effector cells that generally reside in barrier tissues, such as the skin, the gut, and the lung. These cells closely resemble subsets of T lymphocytes, but lack a T cell antigen-receptor. Instead, these cells produce their effector molecules following stimulation by: A. Microbial PAMPs that stimulate pattern recognition receptors on ILCs B. TNF-, which is produced during the inflammatory response C. Acute phase response proteins produced in the liver during an infection D. Cytokines made by other innate cells, such as macrophages or dendritic cells E. Antimicrobial peptides made by epithelial cells in response to infection
D
Mannose binding lectins (MBL) and ficolins are the two classes of proteins that can initiate the lectin pathway of complement activation. These proteins are selective for activating complement on the surfaces of microbial pathogens rather than host cells because: A. Their higher-order oligomeric structure can be assembled only after the monomers first bind to pathogen membranes. B. They only recruit MASP (MBL-associated serine proteases) proteins when bound to pathogen surfaces and not when bound to host cells. C. They only undergo the conformational change needed to activate MASP proteins when bound to a pathogen and not when bound to a host cell. D. They only bind to carbohydrate side chains and oligosaccharide modifications found on pathogen surfaces but not on host cell membranes. E. The activated MASP proteins are rapidly inactivated by hydrolysis when present on the surface of a host cell.
D
Mycobacteria are intracellular pathogens that have adapted to life inside phagocytic cells, such as macrophages. These intracellular bacteria are taken up by phagocytosis, similar to other pathogens, but the bacteria are not killed. One possible mechanism that could account for this immune evasion by mycobacteria is their ability to: A. Prevent induction of nitric oxide production in the phagosome B. Prevent the acidification of phagosomes C. Prevent the expression of antimicrobial peptides in the phagosome D. Prevent fusion of phagosomes with lysosomes E. Kill the macrophage before it kills them
D
One form of anemia results when individuals have a deficiency in the enzyme phosphatidylinositol glycan A (PIGA). This enzyme is required for the membrane attachment of proteins anchored by glycolipids to the plasma membrane, using what is called a 'GPI-linkage.' Included in the group of GPI-linked cell surface proteins is DAF/CD55. These individuals become anemic because: A. DAF/CD55 prevents the lysis of red blood cells by infecting pathogens. B. DAF/CD55 normally prevents the spleen from clearing healthy red blood cells from the circulation. C. In the absence of PIGA, the red blood cell membrane is bare of proteins allowing increased access of complement activating proteins to attach to the cell membrane. D. DAF/CD55 is a complement inhibitory protein that inactivates any C3 convertase that may form on host cell surfaces. E. In the absence of PIGA, red blood cells are unable to synthesize high levels of hemoglobin.
D
The clonal selection theory was first proposed in the 1950s, decades before the molecular details of B and T lymphocyte development and lymphocyte antigen recognition responses were elucidated. Nonetheless, Burnet, who proposed this theory, correctly inferred several key aspects of adaptive immune responses. One key postulate that Burnet proposed was that: A. Cells of the innate immune system are distinct from those of the adaptive immune system. B. Cells of the adaptive immune system are generated from a pluripotent hematopoietic stem cell that resides in the bone marrow. C. B and T lymphocytes are closely related cells that have distinct properties from myeloid cells. D. Circulating antibodies are generated by many different antibody-secreting cells, each of which expresses a single type of antibody on its surface as a receptor. E. Antibodies binding to pathogens lead to efficient pathogen clearance by phagocytic cells.
D
Studies show that about 50-100 different B cells initially seed each germinal center (d7 post-infection). These different B cells are represented by different colored circles in a white oval (germinal center) in the figure below. Which of the choices shown best represents the B cell population that would be found in the same germinal center approximately two weeks later? INSERT PICTURE HERE
D (all teal blue)
Most normal tissues contain resident macrophages, and connective tissue sites in the gastrointestinal tract and the lung contain large numbers of these cells. Yet the blood also contains a high number of circulating 'classical' monocytes that can differentiate into macrophages after entering tissues. These circulating monocytes function to: A. Phagocytose and kill pathogens in the blood B. Line the endothelial surfaces of the blood vessels with phagocytic cells C. Enter lymph nodes and patrol for infecting microbes in these organs D. Amplify the local innate immune response by entering tissues that are infected E. Differentiate into dendritic cells during an inflammatory response
D. Circulating 'classical' monocytes are recruited to enter tissues by the release of cytokines and chemokines resulting from an infection. Once they enter the tissues, the cells differentiate into activated inflammatory monocytes or macrophages, where they can function to phagocytose and destroy pathogens, as well as to produce additional cytokines and chemokines to amplify the local immune response.
Innate lymphoid cells (ILCs) are effector cells that generally reside in barrier tissues, such as the skin, the gut, and the lung. These cells closely resemble subsets of T lymphocytes, but lack a T cell antigen-receptor. Instead, these cells produce their effector molecules following stimulation by: A. Microbial PAMPs that stimulate pattern recognition receptors on ILCs B. TNF-α, which is produced during the inflammatory response C. Acute phase response proteins produced in the liver during an infection D. Cytokines made by other innate cells, such as macrophages or dendritic cells E. Antimicrobial peptides made by epithelial cells in response to infection
D. ILCs function as effector cells that amplify signals produced by innate sensor cells. They are stimulated by cytokines produced by cells such as macrophages and dendritic cells when the macrophages or dendritic cells have been activated by innate sensors of microbial infection or tissue damage.
Mycobacteria are intracellular pathogens that have adapted to life inside phagocytic cells, such as macrophages. These intracellular bacteria are taken up by phagocytosis, similar to other pathogens, but the bacteria are not killed. One possible mechanism that could account for this immune evasion by mycobacteria is their ability to: A. Prevent induction of nitric oxide production in the phagosome B. Prevent the acidification of phagosomes C. Prevent the expression of antimicrobial peptides in the phagosome D. Prevent fusion of phagosomes with lysosomes E. Kill the macrophage before it kills them
D. Once a microbe is phagocytosed by a macrophage, it is sequestered in an intracellular vesicle known as a phagosome. The phagosome then fuses with one or more lysosomes, to form the phagolysosome. The phagolysosome is the compartment which has the capacity to expose the ingested pathogen to acidification, antimicrobial peptides, and reactive oxygen species. These events do not occur in the phagosome prior to its fusion to lysosomes. Mycobacteria have evolved mechanisms to prevent phagosome-lysosome fusion as an immune evasion strategy.
In recent years, several new vaccines have been developed that are made from purified viral surface proteins, rather than intact or live viruses. They are referred to as subunit vaccines. In order to generate a protective adaptive immune response to a subunit vaccine, the viral protein(s) must be mixed with an adjuvant. The adjuvant functions to: A. Mimic the process of normal virus entry by binding to the host receptor and inducing receptor-mediated endocytosis B. Induce vascular permeability to promote the accumulation of fluid and serum proteins at the vaccine injection site C. Induce the production of chemotactic proteins that recruit neutrophils and then monocytes to the site of vaccine injection D. Stimulate dendritic cells to up-regulate co-stimulatory molecules and migrate to the regional lymph node E. Promote the activation of the complement cascade to induce complement deposition on the viral subunit proteins
D. Adjuvants are substances that are mixed with protein antigens to promote their 'immunogenicity' in generating adaptive immune responses. Historically, it was found that adjuvants containing microbial components were the most effective. These compounds stimulate tissue macrophages and dendritic cells to express co-stimulatory molecules. They also stimulate tissue dendritic cells to migrate out of the tissue into the lymph, and traffic to the regional lymph node. These features are essential in generating an adaptive immune response, which is initiated in a lymph node, not in the tissue site. Current efforts to develop new adjuvants for use in subunit vaccines have taken advantage of our knowledge of PAMPs, and which ones are effective at stimulating innate sensors (PRRs) in dendritic cells.
1.20 Multiple choice: The clonal selection theory was first proposed in the 1950s, decades before the molecular details of B and T lymphocyte development and lymphocyte antigen recognition responses were elucidated. Nonetheless, Burnet, who proposed this theory, correctly inferred several key aspects of adaptive immune responses. One key postulate that Burnet proposed was that: A. Cells of the innate immune system are distinct from those of the adaptive immune system. B. Cells of the adaptive immune system are generated from a pluripotent hematopoietic stem cell that resides in the bone marrow. C. B and T lymphocytes are closely related cells that have distinct properties from myeloid cells. D. Circulating antibodies are generated by many different antibody-secreting cells, each of which expresses a single type of antibody on its surface as a receptor. E. Antibodies binding to pathogens lead to efficient pathogen clearance by phagocytic cells.
D. Clonal selection theory was original developed to explain the production of antibodies, as T lymphocytes were not known at that time. A key postulate of the theory was that the body contains a heterogeneous population of lymphocytes, each of which is programmed to produce a single type of antibody. Burnet proposed that each lymphocyte expressed a membrane-bound form of the antibody on its surface as a receptor. Following antigen binding, he proposed that this receptor would induce the proliferative expansion of that lymphocyte into a clone of cells. Each member of this clone of cells would express the identical antibody to the original cell, and all of them would then secrete this antibody.
In patients with lymphomas, the cancer cells invade the bone marrow and destroy the environment required for normal hematopoiesis. This leads to bone marrow failure, which disrupts the production of hematopoietic cell lineages. All of the following cell types would be affected by this EXCEPT: A. Red blood cells B. Macrophages C. Lymphocytes D. Endothelial cells E. Granulocytes
D. Hematopoietic stem cells in the bone marrow give rise to all the blood cell lineages, including erythrocytes (red blood cells), myeloid cells (macrophages and granulocytes), and lymphocytes. Endothelial cells, which comprise the blood vessel walls, are not derived from hematopoietic stem cells.
One form of anemia results when individuals have a deficiency in the enzyme phosphatidylinositol glycan A (PIGA). This enzyme is required for the membrane attachment of proteins anchored by glycolipids to the plasma membrane, using what is called a 'GPI-linkage.' Included in the group of GPI-linked cell surface proteins is DAF/CD55. These individuals become anemic because: A. DAF/CD55 prevents the lysis of red blood cells by infecting pathogens. B. DAF/CD55 normally prevents the spleen from clearing healthy red blood cells from the circulation. C. In the absence of PIGA, the red blood cell membrane is bare of proteins allowing increased access of complement activating proteins to attach to the cell membrane. D. DAF/CD55 is a complement inhibitory protein that inactivates any C3 convertase that may form on host cell surfaces. E. In the absence of PIGA, red blood cells are unable to synthesize high levels of hemoglobin.
D. Host cells express several complement-regulatory proteins on their surface. These proteins function to rapidly inactivate any C3bBb (active C3 convertase) that may form on the host cell membrane. Several of these complement regulatory proteins use GPI-linkages to attach to the host cell membrane. Included in this group is DAF/CD55, which competes with factor B for binding to C3b on the cell surface, and displaces Bb from any active C3 convertase that has already formed. The absence of DAF/CD55 makes host cells susceptible to complement-mediated lysis. For reasons that are not entirely clear, red blood cells are particularly susceptible to complement-mediated lysis and the absence of the GPI-linked subset of complement regulatory proteins is sufficient to cause red blood cell lysis leading to anemia.
Mannose binding lectins (MBL) and ficolins are the two classes of proteins that can initiate the lectin pathway of complement activation. These proteins are selective for activating complement on the surfaces of microbial pathogens rather than host cells because: A. Their higher-order oligomeric structure can be assembled only after the monomers first bind to pathogen membranes. B. They only recruit MASP (MBL-associated serine proteases) proteins when bound to pathogen surfaces and not when bound to host cells. C. They only undergo the conformational change needed to activate MASP proteins when bound to a pathogen and not when bound to a host cell. D. They only bind to carbohydrate side chains and oligosaccharide modifications found on pathogen surfaces but not on host cell membranes. E. The activated MASP proteins are rapidly inactivated by hydrolysis when present on the surface of a host cell.
D. MBL and ficolins have binding specificity for carbohydrate side chains and oligosaccharide modifications that are unique to microbial pathogens, and not found on host cells. MBL binds to mannose, fucose, and GlcNac residues, which are common on microbial glycans; in contrast, MBL does not bind to sialic residues, which terminate vertebrate glycans. Ficolins have specificity for binding to oligosaccharides containing acetylated sugars, a structure also only found on pathogen surfaces, not on host cells.
1.27 Multiple choice: The mucosal tissues of the body have their own unique set of immune structures that function as sites for initiating adaptive immune responses. The necessity for mucosa-associated lymphoid tissues to have unique cell types (M cells) and structures is because: A. The mucous layer lining mucosal surfaces makes it difficult for normal antigen- presenting cells to function. B. The epithelial surfaces that line the gut, lungs, and nasal passages prevent antigen-presenting cells from accessing microbes and microbial products. C. The epithelial cells found in mucosal tissues are distinct from those that provide barrier functions to the skin. D. Mucosal sites, where most pathogens access the body, are exposed to vast numbers of diverse microbes. E. Mucosal tissues lack innate sensor cells that can respond to PAMPs and provide short-term innate immune protection.
D. Mucosal sites, such as the intestine, the reproductive tract, and the lungs are the locations in the body exposed to the greatest numbers and diversities of microbes. Most of those microbes are non-pathogenic, but a subset is capable of causing disease (i.e., is pathogenic). As a consequence, these mucosal sites have developed several unique mechanisms for immune protection. One of these is the presence of M cells that sample the antigens outside the epithelial barrier for surveillance by lymphocytes. Another is the presence of multiple subsets of tissue-resident lymphocytes that provide rapid responses to pathogens that breach the barrier.
The mucosal tissues of the body have their own unique set of immune structures that function as sites for initiating adaptive immune responses. The necessity for mucosa-associated lymphoid tissues to have unique cell types (M cells) and structures is because: A. The mucous layer lining mucosal surfaces makes it difficult for normal antigen-presenting cells to function. B. The epithelial surfaces that line the gut, lungs, and nasal passages prevent antigen-presenting cells from accessing microbes and microbial products. C. The epithelial cells found in mucosal tissues are distinct from those that provide barrier functions to the skin. D. Mucosal sites, where most pathogens access the body, are exposed to vast numbers of diverse microbes. E. Mucosal tissues lack innate sensor cells that can respond to PAMPs and provide short-term innate immune protection.
D. Mucosal sites, such as the intestine, the reproductive tract, and the lungs are the locations in the body exposed to the greatest numbers and diversities of microbes. Most of those microbes are non-pathogenic, but a subset is capable of causing disease (i.e., is pathogenic). As a consequence, these mucosal sites have developed several unique mechanisms for immune protection. One of these is the presence of M cells that sample the antigens outside the epithelial barrier for surveillance by lymphocytes. Another is the presence of multiple subsets of tissue-resident lymphocytes that provide rapid responses to pathogens that breach the barrier.
1.26 Multiple choice: An infant with recurrent bacterial and fungal infections is suspected to have an immunodeficiency disease. Within two days after exposure to a pathogen, the organisms have proliferated to dangerous levels requiring immediate systemic antibiotic treatment. It is unlikely that this infant has a defect in B or T lymphocyte responses to the infection because: A. Bacteria and fungi do not require B cell or T cell responses for their clearance. B. Bacteria and fungi are not efficiently transported to draining lymph nodes to initiate adaptive immune responses. C. Systemic infections of bacteria and fungi are usually cleared by the spleen. D. The defective immune response occurs too rapidly following infection to be due to a defect in B or T lymphocytes responses. E. Adaptive immune responses require dendritic cells to take up and degrade pathogens.
D. The adaptive immune response, consisting of responses by B and T lymphocytes, takes approximately one week to become effective and participate in controlling an infection. The defect in this infant is in the very early innate response, which controls the infection during the first several days after exposure.
An infant with recurrent bacterial and fungal infections is suspected to have an immunodeficiency disease. Within two days after exposure to a pathogen, the organisms have proliferated to dangerous levels requiring immediate systemic antibiotic treatment. It is unlikely that this infant has a defect in B or T lymphocyte responses to the infection because: A. Bacteria and fungi do not require B cell or T cell responses for their clearance. B. Bacteria and fungi are not efficiently transported to draining lymph nodes to initiate adaptive immune responses. C. Systemic infections of bacteria and fungi are usually cleared by the spleen. D. The defective immune response occurs too rapidly following infection to be due to a defect in B or T lymphocytes responses. E. Adaptive immune responses require dendritic cells to take up and degrade pathogens.
D. The adaptive immune response, consisting of responses by B and T lymphocytes, takes approximately one week to become effective and participate in controlling an infection. The defect in this infant is in the very early innate response, which controls the infection during the first several days after exposure.
Multiple choice: IgM is the first antibody isotype secreted following activation of a naive B cell. IgM is found at high concentrations in the serum, and is found as a very high molecular weight complex. This high molecular weight complex is composed of: A. A single IgM monomer plus monomers of IgA and IgG B. A single IgM monomer bound to several non-immunoglobulin serum proteins C. A single IgM monomer bound to serum complement components D. A pentamer of IgM monomers E. Two dimers of IgM plus IgD forming a tetrameric complex
D. A pentamer of IgM monomers
Multiple choice: Most normal tissues contain resident macrophages, and connective tissue sites in the gastrointestinal tract and the lung contain large numbers of these cells. Yet the blood also contains a high number of circulating 'classical' monocytes that can differentiate into macrophages after entering tissues. These circulating monocytes function to: A. Phagocytose and kill pathogens in the blood B. Line the endothelial surfaces of the blood vessels with phagocytic cells C. Enter lymph nodes and patrol for infecting microbes in these organs D. Amplify the local innate immune response by entering tissues that are infected E. Differentiate into dendritic cells during an inflammatory response
D. Amplify the local innate immune response by entering tissues that are infected
Multiple choice: The clonal selection theory was first proposed in the 1950s, decades before the molecular details of B and T lymphocyte development and lymphocyte antigen recognition responses were elucidated. Nonetheless, Burnet, who proposed this theory, correctly inferred several key aspects of adaptive immune responses. One key postulate that Burnet proposed was that: A. Cells of the innate immune system are distinct from those of the adaptive immune system. B. Cells of the adaptive immune system are generated from a pluripotent hematopoietic stem cell that resides in the bone marrow. C. B and T lymphocytes are closely related cells that have distinct properties from myeloid cells. D. Circulating antibodies are generated by many different antibody-secreting cells, each of which expresses a single type of antibody on its surface as a receptor. E. Antibodies binding to pathogens lead to efficient pathogen clearance by phagocytic cells.
D. Circulating antibodies are generated by many different antibody-secreting cells, each of which expresses a single type of antibody on its surface as a receptor.
The clonal selection theory was first proposed in the 1950s, decades before the molecular details of B and T lymphocyte development and lymphocyte antigen recognition responses were elucidated. Nonetheless, Burnet, who proposed this theory, correctly inferred several key aspects of adaptive immune responses. One key postulate that Burnet proposed was that: A. Cells of the innate immune system are distinct from those of the adaptive immune system. B. Cells of the adaptive immune system are generated from a pluripotent hematopoietic stem cell that resides in the bone marrow. C. B and T lymphocytes are closely related cells that have distinct properties from myeloid cells. D. Circulating antibodies are generated by many different antibody-secreting cells, each of which expresses a single type of antibody on its surface as a receptor. E. Antibodies binding to pathogens lead to efficient pathogen clearance by phagocytic cells.
D. Circulating antibodies are generated by many different antibody-secreting cells, each of which expresses a single type of antibody on its surface as a receptor.
Multiple choice: Innate lymphoid cells (ILCs) are effector cells that generally reside in barrier tissues, such as the skin, the gut, and the lung. These cells closely resemble subsets of T lymphocytes, but lack a T cell antigen-receptor. Instead, these cells produce their effector molecules following stimulation by: A. Microbial PAMPs that stimulate pattern recognition receptors on ILCs B. TNF-, which is produced during the inflammatory response C. Acute phase response proteins produced in the liver during an infection D. Cytokines made by other innate cells, such as macrophages or dendritic cells E. Antimicrobial peptides made by epithelial cells in response to infection
D. Cytokines made by other innate cells, such as macrophages or dendritic cells
Multiple choice: One form of anemia results when individuals have a deficiency in the enzyme phosphatidylinositol glycan A (PIGA). This enzyme is required for the membrane attachment of proteins anchored by glycolipids to the plasma membrane, using what is called a 'GPI-linkage.' Included in the group of GPI-linked cell surface proteins is DAF/CD55. These individuals become anemic because: A. DAF/CD55 prevents the lysis of red blood cells by infecting pathogens. B. DAF/CD55 normally prevents the spleen from clearing healthy red blood cells from the circulation. C. In the absence of PIGA, the red blood cell membrane is bare of proteins allowing increased access of complement activating proteins to attach to the cell membrane. D. DAF/CD55 is a complement inhibitory protein that inactivates any C3 convertase that may form on host cell surfaces. E. In the absence of PIGA, red blood cells are unable to synthesize high levels of hemoglobin.
D. DAF/CD55 is a complement inhibitory protein that inactivates any C3 convertase that may form on host cell surfaces.
One form of anemia results when individuals have a deficiency in the enzyme phosphatidylinositol glycan A (PIGA). This enzyme is required for the membrane attachment of proteins anchored by glycolipids to the plasma membrane, using what is called a 'GPI-linkage.' Included in the group of GPI-linked cell surface proteins is DAF/CD55. These individuals become anemic because: A. DAF/CD55 prevents the lysis of red blood cells by infecting pathogens. B. DAF/CD55 normally prevents the spleen from clearing healthy red blood cells from the circulation. C. In the absence of PIGA, the red blood cell membrane is bare of proteins allowing increased access of complement activating proteins to attach to the cell membrane. D. DAF/CD55 is a complement inhibitory protein that inactivates any C3 convertase that may form on host cell surfaces. E. In the absence of PIGA, red blood cells are unable to synthesize high levels of hemoglobin.
D. DAF/CD55 is a complement inhibitory protein that inactivates any C3 convertase that may form on host cell surfaces.
Wiskott-Aldrich syndrome is an immunodeficiency disease due to mutations in the gene encoding WASp. Individuals with this disease make poor antibody responses to protein antigens, due to impaired T cell help for B cells. WASp-deficient T cells are likely impaired in providing adequate help to B cells due to: A. Defects in up-regulating expression of genes encoding cytokines required by B cells B. Defects in up-regulating metabolic pathways for T cell macromolecular synthesis C. Defects in up-regulating expression of genes needed for T cell survival D. Defects in cytoskeletal reorganization needed for directed T cell cytokine secretion E. Defects in up-regulating T cell integrin adhesion for stable interactions with B cells
D. Defects in cytoskeletal reorganization needed for directed T cell cytokine secretion
A mutant B cell line is examined by confocal microscopy after incubation with a microbial pathogen recognized by the BCR on these B cells. The B cells have been stained with antibodies to visualize the localization of polymerized actin and microtubules. As a control, wild-type B cells are examined. The results are shown in Figure Q7.32, with the numbers indicating the proportion of cells examined that show each pattern of staining. To identify the specific signaling defect in these mutant B cells, a reasonable biochemical assay would be to: A. Determine if BCR stimulation of mutant B cells produces enhanced binding of the B cell to the microbe B. Determine whether the mutant B cells have reduced levels of the enzyme Protein kinase C- C. Determine whether the mutant B cells are overexpressing the enzyme Vav D. Determine whether BCR stimulation of mutant B cells promotes exchange of GDP for GTP on cdc42 E. Determine whether BCR stimulation of mutant B cells produces increased levels of DAG
D. Determine whether BCR stimulation of mutatnt B cells promotes exchange of GDP for GTP on cdc42.
In patients with lymphomas, the cancer cells invade the bone marrow and destroy the environment required for normal hematopoiesis. This leads to bone marrow failure, which disrupts the production of hematopoietic cell lineages. All of the following cell types would be affected by this EXCEPT: A. Red blood cells B. Macrophages C. Lymphocytes D. Endothelial cells E. Granulocytes
D. Endothelial cells
In patients with lymphomas, the cancer cells invade the bone marrow and destroy the environment required for normal hematopoiesis. This leads to bone marrow failure, which disrupts the production of hematopoietic cell lineages. All of the following cell types would be affected by this EXCEPT: A.Red blood cells B.Macrophages C.Lymphocytes D.Endothelial cells E.Granulocytes
D. Endothelial cells
Multiple choice: In patients with lymphomas, the cancer cells invade the bone marrow and destroy the environment required for normal hematopoiesis. This leads to bone marrow failure, which disrupts the production of hematopoietic cell lineages. All of the following cell types would be affected by this EXCEPT: A. Red blood cells B. Macrophages C. Lymphocytes D. Endothelial cells E. Granulocytes
D. Endothelial cells
Multiple choice: One striking feature of TCR interactions with peptide:MHC complexes is that amino acid residues in the MHC protein are as important to the TCR binding strength as are amino acid residues in the pathogen-derived peptide. This feature is in contrast to antigen recognition by antibodies, which is a direct interaction that is independent of other host proteins. Based on the different functions of T cells versus antibodies in the adaptive immune response, the fact that TCRs recognize components of both the MHC and the bound peptide exists to: A. Prevent TCRs from binding only to surface exposed epitopes of native pathogens B. Prevent immune evasion by a pathogen that has mutated the sequences required for antibody recognition C. Put constraints on T cell recognition, due to the potentially damaging effector molecules made by activated T cells D. Ensure that TCRs are focused on recognizing antigens associated with host cells, and not those that are free in solution E. Ensure that the pathogen has already been destroyed by the host cell before the T cell will recognize it
D. Ensure that TCRs are focused on recognizing antigens associated with host cells, and not those that are free in solution
Multiple choice: The adaptive immune system uses multiple strategies to generate diversity in our ability to mount responses to a wide array of infectious microorganisms. These strategies include the generation of diverse repertoires of B-cell and T-cell antigen receptors, as well as polymorphism of MHC genes. The polymorphism of MHC genes differs from the diversity of lymphocyte antigen receptors in that: A. It involves DNA rearrangements at multiple gene segments in the MHC locus. B. It requires different enzymes than the RAG1/RAG2 recombinase required for antigen receptor rearrangements. C. It results in a diverse repertoire of clonally distributed receptors on dendritic cells, rather than on lymphocytes. D. It creates diversity between individuals in the population rather than within a single individual. E. It does not contribute to the transplant rejection responses that occur after organ transplantation between unrelated individuals.
D. It creates diversity between individuals in the population rather than within a single individual.
Which of the following statements is TRUE of lysozyme?A.Lysozyme is a cytoplasmic organelle B.Lysozyme activates complement C.Lysozyme is a protease D.Lysozyme splits peptidoglycan E.Lysozyme is released by mast cells
D. Lysozyme splits peptidoglycan
Multiple choice: The mucosal tissues of the body have their own unique set of immune structures that function as sites for initiating adaptive immune responses. The necessity for mucosa-associated lymphoid tissues to have unique cell types (M cells) and structures is because: A. The mucous layer lining mucosal surfaces makes it difficult for normal antigen- presenting cells to function. B. The epithelial surfaces that line the gut, lungs, and nasal passages prevent antigen-presenting cells from accessing microbes and microbial products. C. The epithelial cells found in mucosal tissues are distinct from those that provide barrier functions to the skin. D. Mucosal sites, where most pathogens access the body, are exposed to vast numbers of diverse microbes. E. Mucosal tissues lack innate sensor cells that can respond to PAMPs and provide short-term innate immune protection.
D. Mucosal sites, where most pathogens access the body, are exposed to vast numbers of diverse microbes.
The mucosal tissues of the body have their own unique set of immune structures that function as sites for initiating adaptive immune responses. The necessity for mucosa-associated lymphoid tissues to have unique cell types (M cells) and structures is because: A. The mucous layer lining mucosal surfaces makes it difficult for normal antigen-presenting cells to function. B. The epithelial surfaces that line the gut, lungs, and nasal passages prevent antigen-presenting cells from accessing microbes and microbial products. C. The epithelial cells found in mucosal tissues are distinct from those that provide barrier functions to the skin. D. Mucosal sites, where most pathogens access the body, are exposed to vast numbers of diverse microbes. E. Mucosal tissues lack innate sensor cells that can respond to PAMPs and provide short-term innate immune protection.
D. Mucosal sites, where most pathogens access the body, are exposed to vast numbers of diverse microbes.
Multiple choice: Mycobacteria are intracellular pathogens that have adapted to life inside phagocytic cells, such as macrophages. These intracellular bacteria are taken up by phagocytosis, similar to other pathogens, but the bacteria are not killed. One possible mechanism that could account for this immune evasion by mycobacteria is their ability to: A. Prevent induction of nitric oxide production in the phagosome B. Prevent the acidification of phagosomes C. Prevent the expression of antimicrobial peptides in the phagosome D. Prevent fusion of phagosomes with lysosomes E. Kill the macrophage before it kills them
D. Prevent fusion of phagosomes with lysosomes
Following TCR stimulation, the small GTPase Ras is activated. Ras activation is induced by the Ras GTP-exchange factor (GEF), RasGRP. Both Ras and RasGRP are constitutively expressed in resting T cells. The reason Ras activation is only induced following TCR stimulation is: A. RasGRP undergoes a Ca2+-dependent conformational change required for its activity. B. RasGRP requires tyrosine phosphorylation for its activity. C. RasGRP is ubiquitinated and degraded in the absence of TCR stimulation. D. RasGRP recruitment to the plasma membrane requires TCR stimulation. E. Ras is only recruited to the activated TCR following assembly of the LAT:Gads:SLP-76 complex.
D. RasGRP recruitment to the plasma membrane requires TCR stimulation.
Multiple choice: The innate immune response together with antibodies are generally not effective at clearing infections established by pathogens that replicate inside host cells. The evolution of T cells has provided a means for the immune response to 'see' intracellular infections based on the ability of T cells to: A. Secrete cytokines that diffuse into the infected tissue B. Activate type I interferon production by macrophages and dendritic cells C. Activate macrophages to induce inflammation D. Recognize pathogen-derived peptides on host MHC surface molecules E. Express cytoplasmic sensors for detecting pathogen-derived nucleic acids
D. Recognize pathogen-derived peptides on host MHC surface molecules
The innate immune response together with antibodies are generally not effective at clearing infections established by pathogens that replicate inside host cells. The evolution of T cells has provided a means for the immune response to 'see' intracellular infections based on the ability of T cells to: A. Secrete cytokines that diffuse into the infected tissue B. Activate type I interferon production by macrophages and dendritic cells C. Activate macrophages to induce inflammation D. Recognize pathogen-derived peptides on host MHC surface molecules E. Express cytoplasmic sensors for detecting pathogen-derived nucleic acids
D. Recognize pathogen-derived peptides on host MHC surface molecules
Multiple choice: For alpha:beta T-cell receptors, sequence diversity is heavily concentrated at the junctions formed by the rearrangement of gene segments during the generation of the expressed V and V regions. The result of this organization is to position the most variable part of the T-cell receptor over a certain region of the ligand recognized by this receptor. Which region (outlined in red in Figure Q5.15) indicates this part of the ligand recognized by the T-cell receptor? (SEE IMAGE)
D. SEE IMAGE
Antibody heavy and light chain polypeptides consist of repeated domains, each of which is ~110 amino acids and folds up into a compact three-dimensional structure known as an 'immunoglobulin domain.' These immunoglobulin domains are: A. Mixed and matched between different antibody heavy and light chains to produce variability B. Always identical to each other within a single antibody heavy chain or light chain polypeptide C. Always differ in amino acid sequence between different light chain polypeptides in both of the two light chain immunoglobulin domains D. Similar but not identical in amino acid sequence when comparing the domains in a single heavy chain polypeptide E. Identical in amino acid sequence for every domain when comparing different antibody heavy chain polypeptides to each other
D. Similar but not identical in amino acid sequence when comparing the domains in a single heavy chain polypeptide
Multiple choice: Antibody heavy and light chain polypeptides consist of repeated domains, each of which is ~110 amino acids and folds up into a compact three- dimensional structure known as an 'immunoglobulin domain.' These immunoglobulin domains are: A. Mixed and matched between different antibody heavy and light chains to produce variability B. Always identical to each other within a single antibody heavy chain or light chain polypeptide C. Always differ in amino acid sequence between different light chain polypeptides in both of the two light chain immunoglobulin domains D. Similar but not identical in amino acid sequence when comparing the domains in a single heavy chain polypeptide E. Identical in amino acid sequence for every domain when comparing different antibody heavy chain polypeptides to each other
D. Similar but not identical in amino acid sequence when comparing the domains in a single heavy chain polypeptide
Multiple choice: In recent years, several new vaccines have been developed that are made from purified viral surface proteins, rather than intact or live viruses. They are referred to as subunit vaccines. In order to generate a protective adaptive immune response to a subunit vaccine, the viral protein(s) must be mixed with an adjuvant. The adjuvant functions to: A. Mimic the process of normal virus entry by binding to the host receptor and inducing receptor-mediated endocytosis B. Induce vascular permeability to promote the accumulation of fluid and serum proteins at the vaccine injection site C. Induce the production of chemotactic proteins that recruit neutrophils and then monocytes to the site of vaccine injection D. Stimulate dendritic cells to up-regulate co-stimulatory molecules and migrate to the regional lymph node E. Promote the activation of the complement cascade to induce complement deposition on the viral subunit proteins
D. Stimulate dendritic cells to up-regulate co-stimulatory molecules and migrate to the regional lymph node
Multiple choice: The experiment shown in Figure Q6.19 uses two strains of mice that differ in their MHC genes. Strain A is H-2a and Strain B is H-2b. Mice of each strain are infected with the virus LCMV, and T cells are isolated at day 8 post-infection. These T cells are mixed with target cells that express either H-2a or H-2b; in each case, the target cells are either uninfected or infected with LCMV. After a four-hour incubation of T cells with target cells, the percentage of target cells lysed by the T cells is shown in the graph. (SEE IMAGE) The explanation for the results of this experiment is: A. Mice of strain B do not make a T cell response to LCMV. B. Mice of strain A make a more robust T cell response to LCMV than mice of strain C. Target cells that express H-2b cannot be infected with LCMV. D. T cells from mice of strain A only recognize viral peptides on target cells expressing H-2a. E. LCMV peptides do not bind to MHC class I molecules from H-2b mice.
D. T cells from mice of strain A only recognize viral peptides on target cells expressing H-2a.
Multiple choice: An infant with recurrent bacterial and fungal infections is suspected to have an immunodeficiency disease. Within two days after exposure to a pathogen, the organisms have proliferated to dangerous levels requiring immediate systemic antibiotic treatment. It is unlikely that this infant has a defect in B or T lymphocyte responses to the infection because: A. Bacteria and fungi do not require B cell or T cell responses for their clearance. B. Bacteria and fungi are not efficiently transported to draining lymph nodes to initiate adaptive immune responses. C. Systemic infections of bacteria and fungi are usually cleared by the spleen. D. The defective immune response occurs too rapidly following infection to be due to a defect in B or T lymphocytes responses. E. Adaptive immune responses require dendritic cells to take up and degrade pathogens.
D. The defective immune response occurs too rapidly following infection to be due to a defect in B or T lymphocytes responses.
Multiple choice: Different individuals can have different numbers of functional V gene segments as well as different numbers of constant region genes. This type of genetic polymorphism between individuals indicates that: A. The antibody heavy and light chain loci undergo more frequent mutation than other genes in the genome. B. The recombination machinery is active in germ cells. C. Individuals only need K or upside-down y light chains, but not both. D. The precise number of antibody gene segments in an individual is not important. E. Antibody gene segments underwent more frequent duplication during evolution than other genes in the genome.
D. The precise number of antibody gene segments in an individual is not important.
Multiple choice: Some species, like camels, alpacas, and llamas, have evolved variant forms of immunoglobulin proteins that retain the ability to bind to antigens. While overall the antibodies made by these animals are simpler than human or mouse antibodies, an important feature conserved among all of these antibodies is: A. The presence of both heavy and light chain polypeptides B. Antigen-binding sites comprised of VH and VL sequences C. The presence of exactly three constant region domains D. The presence of two antigen-binding sites per antibody E. The presence of multiple disulfide bonds linking antibody light chains to heavy chains
D. The presence of two antigen-binding sites per antibody
Some species, like camels, alpacas, and llamas, have evolved variant forms of immunoglobulin proteins that retain the ability to bind to antigens. While overall the antibodies made by these animals are simpler than human or mouse antibodies, an important feature conserved among all of these antibodies is: A. The presence of both heavy and light chain polypeptides B. Antigen-binding sites comprised of VH and VL sequences C. The presence of exactly three constant region domains D. The presence of two antigen-binding sites per antibody E. The presence of multiple disulfide bonds linking antibody light chains to heavy chains
D. The presence of two antigen-binding sites per antibody
Multiple choice: Virus infections induce production of interferons that act on infected cells to enhance their recognition by CD8 cytotoxic T cells. To counter these mechanisms, viruses often encode proteins that interfere with antigen processing and presentation. In an experiment, cells infected with Virus X are treated with interferon and compared with uninfected cells treated with interferon. Proteasomes are isolated from the two cell populations and their enzymatic activities are compared. The data in Figure Q6.4 show the amino acid preferences for cleavage of peptides by the two samples of proteasomes. (SEE IMAGE) Based on these data, Virus X most likely encodes a protein that interferes with: A. The expression of MHC class I on the surface of the infected cell B. The rate at which peptides are produced from intact proteins in the infected cell C. The transport of peptides from the cytosol to the endoplasmic reticulum in the infected cell D. The replacement of constitutive proteasome subunits with immunoproteasome subunits in the infected cell E. The development of CD8 T cells in the thymus by inhibiting the thymoproteasome
D. The replacement of constitutive proteasome subunits with immunoproteasome subunits in the infected cell
Mannose binding lectins (MBL) and ficolins are the two classes of proteins that can initiate the lectin pathway of complement activation. These proteins are selective for activating complement on the surfaces of microbial pathogens rather than host cells because: A. Their higher-order oligomeric structure can be assembled only after the monomers first bind to pathogen membranes. B. They only recruit MASP (MBL-associated serine proteases) proteins when bound to pathogen surfaces and not when bound to host cells. C. They only undergo the conformational change needed to activate MASP proteins when bound to a pathogen and not when bound to a host cell. D. They only bind to carbohydrate side chains and oligosaccharide modifications found on pathogen surfaces but not on host cell membranes. E. The activated MASP proteins are rapidly inactivated by hydrolysis when present on the surface of a host cell.
D. They only bind to carbohydrate side chains and oligosaccharide modifications found on pathogen surfaces but not on host cell membranes.
Multiple choice: Mannose binding lectins (MBL) and ficolins are the two classes of proteins that can initiate the lectin pathway of complement activation. These proteins are selective for activating complement on the surfaces of microbial pathogens rather than host cells because: A. Their higher-order oligomeric structure can be assembled only after the monomers first bind to pathogen membranes. B. They only recruit MASP (MBL-associated serine proteases) proteins when bound to pathogen surfaces and not when bound to host cells. C. They only undergo the conformational change needed to activate MASP proteins when bound to a pathogen and not when bound to a host cell. D. They only bind to carbohydrate side chains and oligosaccharide modifications found on pathogen surfaces but not on host cell membranes. E. The activated MASP proteins are rapidly inactivated by hydrolysis when present on the surface of a host cell.
D. They only bind to carbohydrate side chains and oligosaccharide modifications found on pathogen surfaces but not on host cell membranes.
Multiple choice: The variable lymphocyte receptors (VLRs) of lampreys represent a highly diverse set of proteins with structural similarity to the mammalian Toll-like receptors. Yet the VLRs and the lymphocytes that produce them are thought to be components of the lamprey's adaptive immune system. This is because: A. The VLRs are highly diverse and have been shown to bind to pathogens. B. Both membrane-bound and secreted forms of VLRs are found in the lampreys. C. VLR coding genes are formed by DNA rearrangement events. D. VLRs are clonally distributed such that each lymphocyte expresses only one form of VLR. E. VLR gene rearrangements occur by a process similar to gene conversion.
D. VLRs are clonally distributed such that each lymphocyte expresses only one form of VLR.
__________ is an example of a membrane associated complement regulatory factor that acts to prevent attack of 'self' cells/tissues by the complement cascade
DAF
One form of anemia results when individuals have a deficiency in the enzyme phosphatidylinositol glycan A (PIGA). This enzyme is required for the membrane attachment proteins anchored by glycolipids to the plasma membrane, using what is called a 'GPI-linkage.; Included in the group of GPI- linked cell surface proteins is DAF/CD55. These individuals become anemic because:
DAF/CD55 is a complement inhibitory protein that inactivates any C3 convertase
One form of anemia results when individuals have a deficiency in the enzyme phosphatidylinositol glycan A (PIGA). This enzyme is required for the membrane attachment of proteins anchored by glycolipids to the plasma membrane, using what is called a 'GPI-linkage.' Included in the group of GPI-linked cell surface proteins is DAF/CD55. These individuals become anemic because:
DAF/CD55 is a complement inhibitory protein that inactivates any C3 convertase that may form on host cell surfaces.
One form of anemia results when individuals have a deficiency in the enzyme phosphatidylinositol glycan A (PIGA). This enzyme is required for the membrane attachment of proteins anchored by glycolipids to the plasma membrane, using what is called a 'GPI-linkage.' Included in the group of GPI-linked cell surface proteins is DAF/CD55. These individuals become anemic because:
DAF/CD55 is a complement inhibitory protein that inactivates any C3 convertase that may form on host cell surfaces. Host cells express several complement-regulatory proteins on their surface. These proteins function to rapidly inactivate any C3bBb (active C3 convertase) that may form on the host cell membrane. Several of these complement regulatory proteins use GPI- linkages to attach to the host cell membrane. Included in this group is DAF/CD55, which competes with factor B for binding to C3b on the cell surface, and displaces Bb from any active C3 convertase that has already formed. The absence of DAF/CD55 makes host cells susceptible to complement-mediated lysis. For reasons that are not entirely clear, red blood cells are particularly susceptible to complement-mediated lysis and the absence of the GPI-linked subset of complement regulatory proteins is sufficient to cause red blood cell lysis leading to anemia.
Lymphocytes exit the blood and enter the lymph node by extravasating at the high-endothelial venules (HEVs) present in the lymph node cortex. Extravasation does NOT require which of the following?
DCs
Which of the following does NOT occur during dendritic cell maturation?
DCs activate T cells by trafficking from lymph nodes to sites of infection.
An infection in the skin, such as a pimple, often produces pus. The major component of pus is
Dead and dying neutrophils
An infection in the skin, such as a pimple, often produces pus. The major component of pus is:
Dead and dying neutrophils
Which of the following does not occur during an inflammatory response?
Decrease in vascular permeability
Which of the following does not occur during an inflammatory response?
Decreased vascular permeability
Patients with Wiskott-Aldrich syndrome show severely impaired responses to vaccines such as the tetanus vaccine, which is composed of the inactivated tetanus toxin (i.e. tetanus toxoid). Yet, these patients can generate normal antibody responses to bacterial polysaccharide antigens. This selective defect in antibody responses in Wiskott-Aldrich syndrome patients is due to:
Defective polarized secretion of cytokines by CD4 T cells
Match the primary immunodeficiency diseases with the defective mechanism: Leukocyte adhesion deficiency (LAD)
Defects in LFA-1
Match the primary immunodeficiency diseases with the defective mechanism: Bruton's X-linked agammaglobulinemia (XLA)
Defects in gene encoding Bruton's tyrosine kinse
What is Defensin?
Defensin is a antimicrobial peptide that breakdowns cell walls of bacteria directly.
What are defensins and how do they function?
Defensins act within minutes to disrupt the cell membranes of bacteria and fungi, as well as the membrane envelopes of some viruses. The mechanism is thought to involve insertion of the hydrophobic region into the membrane bi-layer and the formation of a pore that makes the membrane leaky
What are Defensins?
Defensins are short cationic peptides of around 30-40 amino acids that usually have three disulfide bonds stabilizing a common amphipathic structure—a positively charged region separated from a hydrophobic region.
Which of the following Ig heavy chains is NOT produced as a result of class switch recombination
Delta
__________ cells are recognized for their ability to bridge the gap between innate and adaptive immunity.
Dendritic
Dendritic cells are phagocytic, but also capable of ingesting large amounts of extracellular fluid and its contents, a process known as macropinocytosis. What specialized function do dendritic cells have in immunity that might account for their need to perform macropinocytosis?
Dendritic cells are essential in T lymphocyte activation so it's important for them to acquire all possible threat categories. Many intact microbes can be taken up by phagocytosis but small toxins produced by pathogens are better dealt with through macropinocytosis.
1.8 Short answer: Dendritic cells are phagocytic, but also capable of ingesting large amounts of extracellular fluid and its contents, a process known as macropinocytosis. What specialized function do dendritic cells have in immunity that might account for their need to perform macropinocytosis?
Dendritic cells are essential in activating T lymphocytes. Therefore, it is important that dendritic cells acquire all possible categories of threats. While many intact microorganisms can be taken up by phagocytosis, small toxins produced by pathogens are more efficiently ingested by macropinocytosis.
Dendritic cells are phagocytic, but also capable of ingesting large amounts of extracellular fluid and its contents, a process known as macropinocytosis. What specialized function do dendritic cells have in immunity that might account for their need to perform macropinocytosis?
Dendritic cells are essential in activating T lymphocytes. Therefore, it is important that dendritic cells acquire all possible categories of threats. While many intact microorganisms can be taken up by phagocytosis, small toxins produced by pathogens are more efficiently ingested by macropinocytosis.
To generate a vaccine to pertussis toxin, a heat-killed preparation of Bordetella pertussis (the bacteria that produce pertussis toxin) is mixed with a purified preparation of the inactivated toxin protein. The mixture is then injected subcutaneously into mice. In an effort to enhance the antibody response to the toxin, a group of test mice is depleted of all their dendritic cells immediately prior to immunization. However, instead of enhancing the antibody response, the dendritic cell depletion nearly eliminated the anti-toxin antibody response because:
Dendritic cells are needed to activate naive CD4 T cells, which can then help the B cells produce anti-toxin antibody
Dendritic cells, also called 'antigen-presenting-cells' are considered the bridge between the innate and the adaptive immune responses. Describe two key features of dendritic cells that are essential for them to provide this bridging function
Dendritic cells respond to infections using innate pattern recognition receptors (PRRs) that recognize PAMPs. Once triggered by PRR stimulation, they migrate from the infected tissue to the regional draining lymph node. Following stimulation of the PRRs the dendritic cells up-regulate co-stimulatory molecules required to activate T lymphocytes. Following uptake the pathogen is degraded and it's peptides are displayed on the surface for recognition by the antigen receptors on T lymphocytes.
In which cells are the IgL loci rearranged by RAG-1/2?
Deveoping B cells
What role do chemokines play in the inflammatory immune response?
Direct neutrophils to the site of infection
A chromosome on which T-cell receptor a chain gene rearrangement has occurred lacks which gene segment?
Diversity (D)
A chromosome on which T-cell receptor α chain gene rearrangement has occurred lacks which of the following gene segments? (Hint: T-cell receptor α chain is comparable to Ig light chain)
Diversity (D)
A chromosome on which T-cell receptor α chain gene rearrangement has occurred lacks which of the following gene segments?(Hint: T-cell receptor αchain is comparable to Ig light chain)
Diversity (D)
B-cell receptor light chain gene locus lacks which of the following gene segments?
Diversity (D)
The Toll-like receptor 3 (TLR3) pattern recognition receptor recognizes:
Double-stranded RNA (dsRNA)
Which of the following options incorrectly describes a mechanism used to prevent fetal rejection?
Downregulation of HLA-G expression by the trophoblast
Many receptors of the immune system activate protein kinases as a mechanism of initiating signaling. For antigen receptors on lymphocytes, ligand binding induces receptor clustering, and the enzymes activated are protein tyrosine kinases. Based on this mechanism, predict the outcome of expressing a mutant form of the receptor-associated tyrosine kinase in cells that still express the wild-type version of this enzyme, and explain your reasoning. This mutant is unable to bind ATP and therefore is catalytically inactive; assume the mutant and wild-type forms of the kinase are expressed in equimolar amounts.
Downstream signaling would be greatly diminished following stimulation of the antigen receptor. This would be visible as reduced auto-phosphorylation of the kinase and reduced phophorylation of downstream substrates of the pathway. In cells with equimolar amounts of wild-type and inactive kinase forms, a majority of receptors would associate with 2 inactive proteins, or 1 active/1 inactive. Few would have 2 active kinases. After receptor clustering, kinase activation normally occurring by 2 associated kinases phosphorylating each other would fail to happen in the majority of receptor complexes. The inactive form of the kinase is known as a 'dominant-negative' mutant, since it can poison signaling even in the presence of the wild-type kinase.
A key feature of TLR signaling is the ability to induce inflammatory cytokine gene expression extremely rapidly following TLR stimulation. This is accomplished by signaling pathways using several mechanisms to activate transcription factors that are already present in the cell prior to TLR stimulation, but are kept in an inactive state. These signaling pathways use all of the following mechanisms EXCEPT: A. Induced ubiquitination leading to protein degradation B. Induced ubiquitination inducing protein-protein interactions C. Induced phosphorylation leading to nuclear translocation D. Induced phosphorylation leading to kinase activation E. Induced phosphorylation preventing protein degradation
E
Given the enormous heterogeneity of antigen receptors expressed on the populations of naive B and T lymphocytes, the adaptive immune response relies on a process whereby the rare lymphocyte that binds to the antigen is first induced to proliferate, before it can perform its effector function. For B cells, there is a clever mechanism that ensures that the specificity of the antibody secreted by the plasma cell will recognize the same pathogen that initially stimulated the B cell antigen receptor and induced B cell proliferation. This mechanism is: A. The naive B cell expresses an array of different B cell antigen receptors, and randomly chooses which specificity of antibody to secrete as a plasma cell. B. The naive B cell expresses a single specificity of B cell antigen receptor, and then up-regulates the expression of this receptor so it can bind tightly to the pathogen. C. The plasma cell proliferates after it has finished secreting antibody to generate more plasma cells with specificity for the pathogen. D. The plasma cell traps secreted antibody molecules in its extracellular matrix and uses these antibodies to bind to the pathogen. E. The naive B cell expresses a membrane-bound form of the antibody as a receptor, and secretes that same antibody when it differentiates into a plasma cell.
E
In healthy adults, neutrophils represent approximately half of their white blood cells. During a bacterial infection, this number often rises to >80%. One factor contributing to this rise is: A. Recruitment of neutrophils from tissues into the blood B. Proliferation of neutrophils at the site of infection C. Proliferation of neutrophils in the blood D. Differentiation of blood monocytes into neutrophils E. Release of neutrophils into the blood from the bone marrow
E
Individuals with defects in T cell development have a severe immunodeficiency disease called SCID (severe combined immunodeficiency disease). In these individuals, the absence of all T cells causes defects in both cell-mediated (T cell-based) and humoral (antibody-based) immune responses. The defect in antibody responses in SCID patients is due to: A. The important role of T cells in regulating B cell development in the bone marrow B. The inter-dependence of T cells and B cells for the normal development of secondary lymphoid organs. C. The absence of phagocytic cells needed for antibody-dependent pathogen clearance in SCID patients D. The poor survival of B cells in patients with defects in their T cells E. The important role of T follicular helper cells in generating protective antibody responses
E
Macrophages express multiple types of receptors on their surface that stimulate phagocytosis of microbes, leading to pathogen internalization and destruction. Many of these receptors, such as Dectin-1, rely on direct recognition of a PAMP on the pathogen surface. However, some receptors that stimulate phagocytosis rely on soluble factors (not associated with the phagocyte membrane) to identify and mark the pathogen for uptake by the phagocyte. One such receptor is: A. The mannose receptor B. The class A scavenger receptor C. The lipid receptor D. The macrophage C-type lectin receptor E. The complement receptor
E
Many different NOD-like receptors, including several with pyrin domains and several with HIN domains, can function to trigger inflammasome assembly leading to the activation of caspase-1. The reason for many different sensors in this innate response system is that: A. Each NOD-like receptor is expressed in a different set of phagocytic cells, depending on its tissue location. B. Each NOD-like receptor resides in a different intracellular compartment. C. Each NOD-like receptor performs a different step in the multi-step cascade leading to inflammasome activation. D. Each NOD-like receptor binds to a different adapter protein and triggers different form of the inflammasome. E. Each NOD-like receptor recognizes different PAMPs and is activated by different pathogens.
E
Many different viruses encode proteins that function to down-regulate MHC class I expression on host cells following infection with the virus. This immune evasion mechanism allows the virus to hide from CD8 T lymphocytes that normally detect virus-infected cells by using their T cell antigen receptor to recognize viral peptides bound to MHC class I proteins on the surface of the infected cell. To counteract this immune evasion strategy, NK cells have: A. Activating receptors that recognize MHC class I proteins B. A mechanism to secrete antiviral peptides C. Inhibitory receptors that recognize viral capsid proteins D. Activating receptors that recognize viral capsid proteins E. Inhibitory receptors that recognize MHC class I proteins
E
Many different viruses encode proteins that function to down-regulate MHC class I expression on host cells following infection with the virus. This immune evasion mechanism allows the virus to hide from CD8 T lymphocytes that normally detect virus-infected cells by using their T cell antigen receptor to recognize viral peptides bound to MHC class I proteins on the surface of the infected cell. To counteract this immune evasion strategy, NK cells have: A. Activating receptors that recognize MHC class I proteins B. A mechanism to secrete antiviral peptides C. Inhibitory receptors that recognize viral capsid proteins D. Activating receptors that recognize viral capsid proteins E. Inhibitory receptors that recognize MHC class I proteins
E
The alternative pathway of complement activation has an important role in innate immunity, due to its ability to greatly amplify the amount of C3b deposited onto the pathogen surface. This amplification occurs because: A. The C3 convertase of the alternative pathway is much more active than those of the classical and lectin pathways. B. The C3 convertase of the alternative pathway works as a soluble enzyme in the plasma. C. The C3 convertase of the alternative pathway cannot be inactivated by complement regulatory factors in the host. D. The C3 convertase of the alternative pathway is more efficiently recruited to pathogen surfaces than the C3 convertases of the classical and lectin pathways. E. The C3 convertase of the alternative pathway contains C3b, and can generate more of itself.
E
The production of antimicrobial peptides is one of the most evolutionarily ancient mechanisms of defense for multicellular organisms, and most eukaryotic species make many different forms of these proteins. For instance, human paneth cells in the gastrointestinal epithelium make 21 different defensins. The reason for this diversity of antimicrobial peptides is: A. Epithelial cells make different forms than those made by neutrophils. B. Neutrophils make many different defensins and store them as inactive proteins in their secretory granules. C. Most of them are produced only in response to infection. D. The production of different peptides is induced following a bacterial infection versus a fungal infection. E. Each one has distinct activities against Gram-negative bacteria, Gram-positive bacteria, or fungi.
E
The terminal components of the complement pathway assemble to form a membrane attack complex that can induce pathogen lysis and death. Yet, evidence indicates that this feature of complement is less important than the earlier steps that promote pathogen opsonization and induce inflammation. This conclusion is based on: A. In vitro experiments showing that very few species of bacteria are susceptible to lysis by the membrane attack complex B. Experiments indicating that only bacteria, but not viruses or fungi, are susceptible to lysis by the membrane attack complex C. The very low levels of terminal complement components in the serum D. The fact that other mammalian species lack the terminal components of the complement pathway needed to form the membrane attack complex E. The limited susceptibility to infections of patients with deficiencies in terminal complement components
E
When complement proteins are covalently deposited onto the surface of a bacterium, this can sometimes lead to direct lysis of the bacterium. However, more commonly, the deposition of complement proteins onto the bacterial surface does not directly harm the bacterium. Instead, these complement proteins aid in bacterial elimination by: A. Recruiting antibodies to the bacterial surface, leading the antibody-dependent neutralization B. Providing a mechanism for phagocytes to use their Fc receptors to recognize and ingest the bacterium C. Cross-linking carbohydrate structures on the bacterial surface, thereby preventing the bacterium from replicating D. Stimulating B lymphocytes to produce more antibodies against the bacterium E. Providing a mechanism for phagocytes bearing complement receptors to recognize and ingest the bacterium
E
Women with urinary tract infections caused by E. coli are generally treated with a course of antibiotics. A common complication of the antibiotic treatment is the occurrence of a vaginal yeast infection caused by Candida albicans, an organism that is normally present in very low numbers in the human vaginal tract. This complication occurs because: A. The E. coli infection damages the reproductive epithelium, causing a breach in the tight junctions and allowing invasion by the Candida albicans. B. The E. coli infection induces adhesion molecule expression on the reproductive epithelium, allowing attachment of the yeast. C. The antibiotic treatment kills all strains of fungi present in the reproductive tract, except the Candida albicans. D. The E. coli infection causes gastrointestinal distress leading to diarrhea. E. The antibiotics kill many of the commensal organisms in the reproductive tract, allowing overgrowth of the fungus.
E
In healthy adults, neutrophils represent approximately half of their white blood cells. During a bacterial infection, this number often rises to >80%. One factor contributing to this rise is: A. Recruitment of neutrophils from tissues into the blood B. Proliferation of neutrophils at the site of infection C. Proliferation of neutrophils in the blood D. Differentiation of blood monocytes into neutrophils E. Release of neutrophils into the blood from the bone marrow
E. Cytokines produced by macrophages in response to a bacterial infection induce leukocytosis, referring to an increase in the numbers of neutrophils circulating in the blood. These neutrophils come from two sources. First, increased numbers of neutrophils are released from the bone marrow, their normal site of maturation. Second, neutrophils are released from sites in blood vessels, where they are loosely attached to endothelial cells.
An infection in the skin, such as a pimple, often produces pus. The major component of pus is: A. Toxic oxygen molecules released by macrophages B. Toxic nitrogen molecules released by macrophages C. NETs released by neutrophils D. Dead epithelial cells killed by lysozyme E. Dead and dying neutrophils
E. Neutrophils are recruited in large numbers to sites of infection. These cells are short-lived (<1 day) and die shortly after a round of phagocytosis when they have used up their primary and secondary granules. Infections of extracellular encapsulated bacteria, such as streptococci and staphylococci, recruit large numbers of neutrophils, and are known as pus-forming bacteria.
A key feature of TLR signaling is the ability to induce inflammatory cytokine gene expression extremely rapidly following TLR stimulation. This is accomplished by signaling pathways using several mechanisms to activate transcription factors that are already present in the cell prior to TLR stimulation, but are kept in an inactive state. These signaling pathways use all of the following mechanisms EXCEPT: A. Induced ubiquitination leading to protein degradation B. Induced ubiquitination inducing protein-protein interactions C. Induced phosphorylation leading to nuclear translocation D. Induced phosphorylation leading to kinase activation E. Induced phosphorylation preventing protein degradation
E. TLR signaling pathways lead to the activation of NFκB and of IRF family transcription factors. Each pathway has multiple steps, beginning with the adapter proteins MyD88, MAL, TRAM, and TRIF in various combinations. These steps include both K48-linked and K63-linked ubiquitination, resulting in protein degradation or protein-protein interactions, respectively. Also included are steps of protein phosphorylation, leading to nuclear localization of the IRF factors, and leading to kinase activation for TAK1. None of these steps include a process whereby protein phosphorylation stabilizes protein turnover by preventing degradation.
Macrophages express multiple types of receptors on their surface that stimulate phagocytosis of microbes, leading to pathogen internalization and destruction. Many of these receptors, such as Dectin-1, rely on direct recognition of a PAMP on the pathogen surface. However, some receptors that stimulate phagocytosis rely on soluble factors (not associated with the phagocyte membrane) to identify and mark the pathogen for uptake by the phagocyte. One such receptor is: A. The mannose receptor B. The class A scavenger receptor C. The lipid receptor D. The macrophage C-type lectin receptor E. The complement receptor
E. The complement receptor expressed on phagocytes binds to complement-coated pathogens. A pathogen becomes opsonized with complement proteins when it is first recognized by an initiating member of the complement pathway, such as MBL, other collectins or ficolins, or by antibody. Another example of a receptor on phagocytes that stimulates phagocytosis but does not directly recognize the pathogen surface is one of the Fc receptors.
Women with urinary tract infections caused by E. coli are generally treated with a course of antibiotics. A common complication of the antibiotic treatment is the occurrence of a vaginal yeast infection caused by Candida albicans, an organism that is normally present in very low numbers in the human vaginal tract. This complication occurs because: A. The E. coli infection damages the reproductive epithelium, causing a breach in the tight junctions and allowing invasion by the Candida albicans. B. The E. coli infection induces adhesion molecule expression on the reproductive epithelium, allowing attachment of the yeast. C. The antibiotic treatment kills all strains of fungi present in the reproductive tract, except the Candida albicans. D. The E. coli infection causes gastrointestinal distress leading to diarrhea. E. The antibiotics kill many of the commensal organisms in the reproductive tract, allowing overgrowth of the fungus.
E. Commensal organisms associated with all epithelial surfaces provide protection against colonization by pathogenic microbes. One mechanism is by competition for nutrients as well as for attachment sites on epithelial surfaces. Another mechanism is by producing metabolites that are toxic to other organisms. When these commensal microorganisms are eliminated by antibiotic treatment, pathogenic microbes are able to step into the void and establish an infection.
1.34 Multiple choice: When complement proteins are covalently deposited onto the surface of a bacterium, this can sometimes lead to direct lysis of the bacterium. However, more commonly, the deposition of complement proteins onto the bacterial surface does not directly harm the bacterium. Instead, these complement proteins aid in bacterial elimination by: A. Recruiting antibodies to the bacterial surface, leading the antibody-dependent neutralization B. Providing a mechanism for phagocytes to use their Fc receptors to recognize and ingest the bacterium C. Cross-linking carbohydrate structures on the bacterial surface, thereby preventing the bacterium from replicating D. Stimulating B lymphocytes to produce more antibodies against the bacterium E. Providing a mechanism for phagocytes bearing complement receptors to recognize and ingest the bacterium
E. In most cases, the protective immune response elicited by a complement-tagged bacterium is the uptake and degradation of the bacterium by phagocytes expressing complement receptors. This includes both macrophages and neutrophils, both of which express complement receptors. In addition to aiding in bacterial engulfment, binding of the complement proteins on the bacterium to the complement receptors on the phagocyte can also enhance the production of microbicidal effector functions in the phagocyte.
When complement proteins are covalently deposited onto the surface of a bacterium, this can sometimes lead to direct lysis of the bacterium. However, more commonly, the deposition of complement proteins onto the bacterial surface does not directly harm the bacterium. Instead, these complement proteins aid in bacterial elimination by: A. Recruiting antibodies to the bacterial surface, leading the antibody-dependent neutralization B. Providing a mechanism for phagocytes to use their Fc receptors to recognize and ingest the bacterium C. Cross-linking carbohydrate structures on the bacterial surface, thereby preventing the bacterium from replicating D. Stimulating B lymphocytes to produce more antibodies against the bacterium E. Providing a mechanism for phagocytes bearing complement receptors to recognize and ingest the bacterium
E. In most cases, the protective immune response elicited by a complement-tagged bacterium is the uptake and degradation of the bacterium by phagocytes expressing complement receptors. This includes both macrophages and neutrophils, both of which express complement receptors. In addition to aiding in bacterial engulfment, binding of the complement proteins on the bacterium to the complement receptors on the phagocyte can also enhance the production of microbicidal effector functions in the phagocyte.
The terminal components of the complement pathway assemble to form a membrane attack complex that can induce pathogen lysis and death. Yet, evidence indicates that this feature of complement is less important than the earlier steps that promote pathogen opsonization and induce inflammation. This conclusion is based on: A. In vitro experiments showing that very few species of bacteria are susceptible to lysis by the membrane attack complex B. Experiments indicating that only bacteria, but not viruses or fungi, are susceptible to lysis by the membrane attack complex C. The very low levels of terminal complement components in the serum D. The fact that other mammalian species lack the terminal components of the complement pathway needed to form the membrane attack complex E. The limited susceptibility to infections of patients with deficiencies in terminal complement components
E. Patients with genetic deficiencies in terminal complement components show only a limited increase in susceptibility to infection. These individuals are more susceptible to infection by Neisseria species that cause gonorrhea or meningitis. Otherwise, these individuals show no other increased susceptibility to infection, indicating that formation of the membrane attack complex is a less important aspect of complement activation compared to the earlier steps that lead to opsonization of the pathogen as well as inducing inflammation.
1.37 Multiple choice: Individuals with defects in T cell development have a severe immunodeficiency disease called SCID (severe combined immunodeficiency disease). In these individuals, the absence of all T cells causes defects in both cell-mediated (T cell- based) and humoral (antibody-based) immune responses. The defect in antibody responses in SCID patients is due to: A. The important role of T cells in regulating B cell development in the bone marrow B. The inter-dependence of T cells and B cells for the normal development of secondary lymphoid organs. C. The absence of phagocytic cells needed for antibody-dependent pathogen clearance in SCID patients D. The poor survival of B cells in patients with defects in their T cells E. The important role of T follicular helper cells in generating protective antibody responses
E. T follicular helper cells are a subset of CD4 T cell that provide signals needed for B cell activation and the generation of protective antibody responses to most infections. In the absence of T cells, antibody responses are poor and generally not sufficient for pathogen clearance.
Individuals with defects in T cell development have a severe immunodeficiency disease called SCID (severe combined immunodeficiency disease). In these individuals, the absence of all T cells causes defects in both cell-mediated (T cell-based) and humoral (antibody-based) immune responses. The defect in antibody responses in SCID patients is due to: A. The important role of T cells in regulating B cell development in the bone marrow B. The inter-dependence of T cells and B cells for the normal development of secondary lymphoid organs. C. The absence of phagocytic cells needed for antibody-dependent pathogen clearance in SCID patients D. The poor survival of B cells in patients with defects in their T cells E. The important role of T follicular helper cells in generating protective antibody responses
E. T follicular helper cells are a subset of CD4 T cell that provide signals needed for B cell activation and the generation of protective antibody responses to most infections. In the absence of T cells, antibody responses are poor and generally not sufficient for pathogen clearance.
Given the enormous heterogeneity of antigen receptors expressed on the populations of naive B and T lymphocytes, the adaptive immune response relies on a process whereby the rare lymphocyte that binds to the antigen is first induced to proliferate, before it can perform its effector function. For B cells, there is a clever mechanism that ensures that the specificity of the antibody secreted by the plasma cell will recognize the same pathogen that initially stimulated the B cell antigen receptor and induced B cell proliferation. This mechanism is: A. The naive B cell expresses an array of different B cell antigen receptors, and randomly chooses which specificity of antibody to secrete as a plasma cell. B. The naive B cell expresses a single specificity of B cell antigen receptor, and then up-regulates the expression of this receptor so it can bind tightly to the pathogen. C. The plasma cell proliferates after it has finished secreting antibody to generate more plasma cells with specificity for the pathogen. D. The plasma cell traps secreted antibody molecules in its extracellular matrix and uses these antibodies to bind to the pathogen. E. The naive B cell expresses a membrane-bound form of the antibody as a receptor, and secretes that same antibody when it differentiates into a plasma cell.
E. The B cell antigen receptor includes a membrane-bound form of the antibody protein and two transmembrane subunits that provide receptor signaling functions. When a B cell binds to a pathogen using this receptor, the B cell divides differentiates into a plasma cell. As a plasma cell, this B cell generates a secreted form of this same antibody protein by eliminating the transmembrane domains that anchor the antibody protein into the B cell membrane.
1.14 Multiple choice: Given the enormous heterogeneity of antigen receptors expressed on the populations of naive B and T lymphocytes, the adaptive immune response relies on a process whereby the rare lymphocyte that binds to the antigen is first induced to proliferate, before it can perform its effector function. For B cells, there is a clever mechanism that ensures that the specificity of the antibody secreted by the plasma cell will recognize the same pathogen that initially stimulated the B cell antigen receptor and induced B cell proliferation. This mechanism is: A. The naive B cell expresses an array of different B cell antigen receptors, and randomly chooses which specificity of antibody to secrete as a plasma cell. B. The naive B cell expresses a single specificity of B cell antigen receptor, and then up-regulates the expression of this receptor so it can bind tightly to the pathogen. C. The plasma cell proliferates after it has finished secreting antibody to generate more plasma cells with specificity for the pathogen. D. The plasma cell traps secreted antibody molecules in its extracellular matrix and uses these antibodies to bind to the pathogen. E. The naive B cell expresses a membrane-bound form of the antibody as a receptor, and secretes that same antibody when it differentiates into a plasma cell.
E. The B cell antigen receptor includes a membrane-bound form of the antibody protein, along with two transmembrane subunits that provide receptor signaling functions. When a given B cell binds to a pathogen using its B cell antigen receptor, the B cell is stimulated to proliferate and differentiate into a plasma cell. As a plasma cell, this B cell generates a secreted form of this same antibody protein by eliminating the transmembrane domains that anchor the antibody protein into the B cell membrane.
The alternative pathway of complement activation has an important role in innate immunity, due to its ability to greatly amplify the amount of C3b deposited onto the pathogen surface. This amplification occurs because: A. The C3 convertase of the alternative pathway is much more active than those of the classical and lectin pathways. B. The C3 convertase of the alternative pathway works as a soluble enzyme in the plasma. C. The C3 convertase of the alternative pathway cannot be inactivated by complement regulatory factors in the host. D. The C3 convertase of the alternative pathway is more efficiently recruited to pathogen surfaces than the C3 convertases of the classical and lectin pathways. E. The C3 convertase of the alternative pathway contains C3b, and can generate more of itself.
E. The C3 convertase (C3bBb) of the alternative pathway contains C3b, allowing it to generate more of itself and amplify the overall level of C3b formed. Once additional molecules of C3b are made by C3bBb, these can recruit additional molecules of factor B and the plasma protease factor D. Factor D cleaves factor B, and one of the products, Bb, remains associated with C3b, forming more active C3 convertase.
The production of antimicrobial peptides is one of the most evolutionarily ancient mechanisms of defense for multicellular organisms, and most eukaryotic species make many different forms of these proteins. For instance, human paneth cells in the gastrointestinal epithelium make 21 different defensins. The reason for this diversity of antimicrobial peptides is: A. Epithelial cells make different forms than those made by neutrophils. B. Neutrophils make many different defensins and store them as inactive proteins in their secretory granules. C. Most of them are produced only in response to infection. D. The production of different peptides is induced following a bacterial infection versus a fungal infection. E. Each one has distinct activities against Gram-negative bacteria, Gram-positive bacteria, or fungi.
E. The diversity of antimicrobial peptides is a reflection of the diversity of microbial pathogens that they attack. Some antimicrobial peptides are active against Gram-negative bacteria, while others are only active against Gram-positive bacteria. Other antimicrobial peptides are only active against fungal pathogens, and some are able to disrupt the membrane envelopes of some viruses.
Multiple choice: In a mixed lymphocyte reaction, T cells from individual A make a robust response to antigen-presenting-cells from individual B, as long as the two individuals express different alleles of MHC molecules. Estimates indicate that up to 10% of the T cells from individual A may contribute to this response. If one performed this assay using responder T cells from a child and antigen-presenting cells from one parent, the result would be: A. A massive proliferative response made by the antigen-presenting cells of the parent B. A very weak response by the child's T cells, involving only 0.1% of their T cells C. The complete absence of any proliferative response by the child's T cells D. A robust cytolytic response that kills all of the parent's antigen-presenting cells E. A robust response by the child's T cells
E. A robust response by the child's T cells
Multiple choice: When a mixture of different IgG antibody proteins are treated with the enzyme papain, each antibody is cleaved into three roughly equal size fragments. From each original antibody, two of the three fragments are identical to each other, and represent the 'arms' of the antibody 'Y'. These fragments are known as Fab fragments. The third fragment is known as the Fc region, because this fragment will crystallize when purified. The reason a mixture of Fc fragments will crystallize is because: A. It is the only part of the antibody protein that can easily be purified at the high concentrations needed for crystallization. B. It has no disulfide bonds holding the domains together, as disulfide bonds will inhibit crystallization. C. It is the only fragment of the antibody that still has disulfide bonds, so it remains intact during the crystallization process. D. The Fc fragments of IgG are much more water soluble than the Fab fragments. E. All Fc fragments generated from a mixture of IgG molecules have the identical amino acid sequence.
E. All Fc fragments generated from a mixture of IgG molecules have the identical amino acid sequence.
When a mixture of different IgG antibody proteins are treated with the enzyme papain, each antibody is cleaved into three roughly equal size fragments. From each original antibody, two of the three fragments are identical to each other, and represent the 'arms' of the antibody 'Y'. These fragments are known as Fab fragments. The third fragment is known as the Fc region, because this fragment will crystallize when purified. The reason a mixture of Fc fragments will crystallize is because: A. It is the only part of the antibody protein that can easily be purified at the high concentrations needed for crystallization. B. It has no disulfide bonds holding the domains together, as disulfide bonds will inhibit crystallization. C. It is the only fragment of the antibody that still has disulfide bonds, so it remains intact during the crystallization process. D. The Fc fragments of IgG are much more water soluble than the Fab fragments. E. All Fc fragments generated from a mixture of IgG molecules have the identical amino acid sequence.
E. All Fc fragments generated from a mixture of IgG molecules have the identical amino acid sequence.
Multiple choice: In some vertebrates, such as rays and some shark species, immunoglobulin light chain genes consist of multiple units of already rearranged VJ-C genes, of which one is chosen for expression in a developing B cell. This strategy may have evolved in these organisms: A. Prior to the evolution of rearranging gene segments requiring somatic recombination in developing B cells B. Prior to the evolution of the RAG1 and RAG2 enzymes needed for recombination C. As a mechanism to increase light chain diversity beyond that achieved by the use of rearranging gene segments in humans D. As a mechanism to increase light chain diversity beyond that achieved the gene conversion process used in chickens E. As a means to generate a rapid response to common pathogens encountered by these animals
E. As a means to generate a rapid response to common pathogens encountered by these animals
A new strain of immunodeficient mice has been discovered, and found to have T cells that are unresponsive to TCR stimulation. The T cells from these mice have normal levels of the TCR complex on their surface, but when this TCR is stimulated, the cells fail to secrete IL-2. As a first step in determining the signaling defect responsible for this immunodeficiency, the T cells are stimulated with a phorbol ester (PMA) and Ionomycin. It is found that this treatment elicits IL-2 production by the immunodeficient T cells. Based on this information, candidate genes that could be mutated in these T cells include all of the following EXCEPT: A. ZAP-70 B. PLC- C. SLP-76 D. ITK E. Calcineurin
E. Calcineurin
Antigen receptor signaling pathways are initiated by the action of a Src-family kinase. In T cells, the predominant Src-kinase is Lck. In resting T cells, Lck is maintained in an inactive state by allosteric interactions involving multiple domains of the enzyme. When T cells are treated with a small molecule inhibitor of the tyrosine kinase Csk, TCR signaling is initiated even in the absence of a ligand to stimulate the TCR. This occurs because: A. Csk phosphorylates Lck in its kinase domain, leading to Lck activation. B. Csk phosphorylates ZAP-70, maintaining ZAP-70 in an auto-inhibited state. C. Csk phosphorylates the ITAM motifs in the TCR chain, leading to ZAP-70 recruitment. D. Csk phosphorylates and activates the membrane tyrosine phosphatase CD45. E. Csk phosphorylates the C-terminal negative regulatory tyrosine in Lck.
E. Csk phosphorylates the C-terminal negative regulatory tyrosine in Lck
Multiple choice: An infection in the skin, such as a pimple, often produces pus. The major component of pus is: A. Toxic oxygen molecules released by macrophages B. Toxic nitrogen molecules released by macrophages C. NETs released by neutrophils D. Dead epithelial cells killed by lysozyme E. Dead and dying neutrophils
E. Dead and dying neutrophils
Multiple choice: Many different NOD-like receptors, including several with pyrin domains and several with HIN domains, can function to trigger inflammasome assembly leading to the activation of caspase-1. The reason for many different sensors in this innate response system is that: A. Each NOD-like receptor is expressed in a different set of phagocytic cells, depending on its tissue location. B. Each NOD-like receptor resides in a different intracellular compartment. C. Each NOD-like receptor performs a different step in the multi-step cascade leading to inflammasome activation. D. Each NOD-like receptor binds to a different adapter protein and triggers a different form of the inflammasome. E. Each NOD-like receptor recognizes different PAMPs and is activated by different pathogens.
E. Each NOD-like receptor recognizes different PAMPs and is activated by different pathogens.
Multiple choice: The production of antimicrobial peptides is one of the most evolutionarily ancient mechanisms of defense for multicellular organisms, and most eukaryotic species make many different forms of these proteins. For instance, human paneth cells in the gastrointestinal epithelium make 21 different defensins. The reason for this diversity of antimicrobial peptides is: A. Epithelial cells make different forms than those made by neutrophils. B. Neutrophils make many different defensins and store them as inactive proteins in their secretory granules. C. Most of them are produced only in response to infection. D. The production of different peptides is induced following a bacterial infection versus a fungal infection. E. Each one has distinct activities against Gram-negative bacteria, Gram-positive bacteria, or fungi.
E. Each one has distinct activities against Gram-negative bacteria, Gram-positive bacteria, or fungi.
The production of antimicrobial peptides is one of the most evolutionarily ancient mechanisms of defense for multicellular organisms, and most eukaryotic species make many different forms of these proteins. For instance, human paneth cells in the gastrointestinal epithelium make 21 different defensins. The reason for this diversity of antimicrobial peptides is: A. Epithelial cells make different forms than those made by neutrophils. B. Neutrophils make many different defensins and store them as inactive proteins in their secretory granules. C. Most of them are produced only in response to infection. D. The production of different peptides is induced following a bacterial infection versus a fungal infection. E. Each one has distinct activities against Gram-negative bacteria, Gram-positive bacteria, or fungi.
E. Each one has distinct activities against Gram-negative bacteria, Gram-positive bacteria, or fungi.
One striking feature of TCR interactions with peptide:MHC complexes is that amino acid residues in the MHC protein are as important to the TCR binding strength as are amino acid residues in the pathogen-derived peptide. This feature is in contrast to antigen recognition by antibodies, which is a direct interaction that is independent of other host proteins. Based on the different functions of T cells versus antibodies in the adaptive immune response, the fact that TCRs recognize components of both the MHC and the bound peptide exists to: A. Prevent TCRs from binding only to surface exposed epitopes of native pathogens B. Prevent immune evasion by a pathogen that has mutated the sequences required for antibody recognition C. Put constraints on T cell recognition, due to the potentially damaging effector molecules made by activated T cells D. Ensure that TCRs are focused on recognizing antigens associated with host cells, and not those that are free in solution E. Ensure that the pathogen has already been destroyed by the host cell before the T cell will recognize it
E. Ensure that TCRs are focused on recognizing antigens associated with host cells, and not those that are free in solution
Multiple choice: Empty MHC class I and MHC class II molecules are rapidly removed from the cell surface. This process prevents: A. The accumulation of empty MHC molecules on the cell surface which would interfere with T cells recognizing pathogen-derived peptide:MHC complexes B. Pathogens from evading the immune response by inducing peptide release from cell surface MHC molecules C. MHC class I molecules from being internalized into endosomes and binding endosome-derived peptides D. HLA-DM from trafficking to the cell surface with MHC class II E. Inappropriate T cell recognition of healthy cells that are not infected, nor have ingested a pathogen
E. Inappropriate T cell recognition of healthy cells that are not infected, nor have ingested a pathogen
Multiple choice: A key feature of TLR signaling is the ability to induce inflammatory cytokine gene expression extremely rapidly following TLR stimulation. This is accomplished by signaling pathways using several mechanisms to activate transcription factors that are already present in the cell prior to TLR stimulation, but are kept in an inactive state. These signaling pathways use all of the following mechanisms EXCEPT: A. Induced ubiquitination leading to protein degradation B. Induced ubiquitination inducing protein-protein interactions C. Induced phosphorylation leading to nuclear translocation D. Induced phosphorylation leading to kinase activation E. Induced phosphorylation preventing protein degradation
E. Induced phosphorylation preventing protein degradation
Multiple choice: Many different viruses encode proteins that function to down-regulate MHC class I expression on host cells following infection with the virus. This immune evasion mechanism allows the virus to hide from CD8 T lymphocytes that normally detect virus-infected cells by using their T cell antigen receptor to recognize viral peptides bound to MHC class I proteins on the surface of the infected cell. To counteract this immune evasion strategy, NK cells have: A. Activating receptors that recognize MHC class I proteins B. A mechanism to secrete antiviral peptides C. Inhibitory receptors that recognize viral capsid proteins D. Activating receptors that recognize viral capsid proteins E. Inhibitory receptors that recognize MHC class I proteins
E. Inhibitory receptors that recognize MHC class I proteins
An important transcription factor activated by antigen receptor signaling in lymphocytes is an NFkB heterodimer of the two subunits, p50 and p65Rel. Defects in the IkB-kinase complex (NEMO) or mutations in IkB that prevent its phosphorylation interfere with NFkB activation and result in severe immunodeficiency diseases. This is due to the important function of: A. NEMO in targeting p50:p65Rel for ubiquitination and degradation B. NEMO in ubiquitinating IB causing its release from NFB C. IkB in blocking the DNA binding activity of NFkB D. IkB as a chaperone to promote NFkB nuclear localization E. NEMO in phosphorylating IkB inducing its degradation, thereby releasing NFkB
E. NEMO in phosphorylating IkB inducing its degradation, thereby releasing NFkB
Multiple choice: During MHC class I synthesis and folding in the endoplasmic reticulum (ER), a process of peptide editing takes place as the newly synthesized MHC class I protein is held in a 'peptide receptive' state by binding to the calreticulin:ERp57:tapasin complex. Peptide editing ensures that the MHC class I molecules that reach the cell surface have stable, high affinity binding for their peptide cargo. Peptide editing is important to the immune response because it: A. Maintains high levels of surface MHC class I expression B. Ensures that MHC class I molecules are not degraded in the ER C. Retains the nascent MHC class I molecule in a peptide receptive state D. Allows surface MHC class I molecules to bind new peptides from the extracellular milieu E. Prevents surface MHC class I molecules from undergoing peptide exchange at the cell surface
E. Prevents surface MHC class I molecules from undergoing peptide exchange at the cell surface
Multiple choice: When complement proteins are covalently deposited onto the surface of a bacterium, this can sometimes lead to direct lysis of the bacterium. However, more commonly, the deposition of complement proteins onto the bacterial surface does not directly harm the bacterium. Instead, these complement proteins aid in bacterial elimination by: A. Recruiting antibodies to the bacterial surface, leading the antibody-dependent neutralization B. Providing a mechanism for phagocytes to use their Fc receptors to recognize and ingest the bacterium C. Cross-linking carbohydrate structures on the bacterial surface, thereby preventing the bacterium from replicating D. Stimulating B lymphocytes to produce more antibodies against the bacterium E. Providing a mechanism for phagocytes bearing complement receptors to recognize and ingest the bacterium
E. Providing a mechanism for phagocytes bearing complement receptors to recognize and ingest the bacterium
When complement proteins are covalently deposited onto the surface of a bacterium, this can sometimes lead to direct lysis of the bacterium. However, more commonly, the deposition of complement proteins onto the bacterial surface does not directly harm the bacterium. Instead, these complement proteins aid in bacterial elimination by: A. Recruiting antibodies to the bacterial surface, leading the antibody-dependent neutralization B. Providing a mechanism for phagocytes to use their Fc receptors to recognize and ingest the bacterium C. Cross-linking carbohydrate structures on the bacterial surface, thereby preventing the bacterium from replicating D. Stimulating B lymphocytes to produce more antibodies against the bacterium E. Providing a mechanism for phagocytes bearing complement receptors to recognize and ingest the bacterium
E. Providing a mechanism for phagocytes bearing complement receptors to recognize and ingest the bacterium.
Multiple choice: In healthy adults, neutrophils represent approximately half of their white blood cells. During a bacterial infection, this number often rises to >80%. One factor contributing to this rise is: A. Recruitment of neutrophils from tissues into the blood B. Proliferation of neutrophils at the site of infection C. Proliferation of neutrophils in the blood D. Differentiation of blood monocytes into neutrophils E. Release of neutrophils into the blood from the bone marrow
E. Release of neutrophils into the blood from the bone marrow
Multiple choice: Several invertebrate species, such as some insect and snail species, have mechanisms for increasing the diversity of immune recognition molecules that are expressed in an individual beyond the simple 'one gene encodes one protein' rule that applies to most genes in the genome. One of these mechanisms: A. Uses a pair of enzymes that are related to the RAG recombinase enzymes found in vertebrates B. Creates a library of complement proteins that function like vertebrate complement to promote phagocytosis of microbes by macrophages and neutrophils C. Creates a clonally distributed set of immune recognition molecules by a process involving different DNA rearrangement events in each cell D. Uses a mechanism in which a small number of cells expressing a few different proteins undergo massive proliferation to provide protective immunity E. Resembles the V-D-J recombination process in vertebrates but occurs by differential RNA splicing rather than by DNA rearrangement
E. Resembles the V-D-J recombination process in vertebrates but occurs by differential RNA splicing rather than by DNA rearrangement
Multiple choice: The addition and subtraction of nucleotides at the junctions between V, D, and J gene segments creates antibody proteins with wide variations in the numbers of amino acids in their CDR3 regions. This variability in CDR3 length is important as: A. Overall variability in CDR3 sequence is needed to create a sufficiently diverse antibody repertoire. B. The CDR3 region is more important in binding antigen than the CDR1 and CDR2 regions are. C. Some light chains bind better to heavy chains with longer CDR3 region sequences. D. Longer CDR3 sequences generally create antibodies with higher affinity for the antigen. E. Some antibodies bind relatively flat surfaces and others bind deep clefts in the antigen.
E. Some antibodies bind relatively flat surfaces and others bind deep clefts in the antigen.
Multiple choice: Antibodies that bind with high affinity to some viral surface proteins require heavy chain CDR3 loops of unusual length. Whereas the average human heavy chain CDR3 length is ~15 amino acids, antibodies with VH CDR3 loops of >30 amino acids are readily detected in the repertoire. These antibody heavy chains with CDR3 lengths of >30 amino acids would likely be missing in individuals lacking: A. RAG-1 and RAG-2 B. DNA-dependent protein kinase (DNA-PK) C. The nuclease, Artemis D. The Ku70:Ku80 complex E. Terminal deoxy nucleotidyl transferase (TdT)
E. Terminal deoxy nucleotidyl transferase (TdT)
The alternative pathway of complement activation has an important role in innate immunity, due to its ability to greatly amplify the amount of C3b deposited onto the pathogen surface. This amplification occurs because: A. The C3 convertase of the alternative pathway is much more active than those of the classical and lectin pathways. B. The C3 convertase of the alternative pathway works as a soluble enzyme in the plasma. C. The C3 convertase of the alternative pathway cannot be inactivated by complement regulatory factors in the host. D. The C3 convertase of the alternative pathway is more efficiently recruited to pathogen surfaces than the C3 convertases of the classical and lectin pathways. E. The C3 convertase of the alternative pathway contains C3b, and can generate more of itself.
E. The C3 convertase of the alternative pathway contains C3b, and can generate more of itself
The alternative pathway of complement activation has an important role in innate immunity, due to its ability to greatly amplify the amount of C3b deposited onto the pathogen surface. This amplification occurs because: A.The C3 convertase of the alternative pathway is much more active than those of the classical and lectin pathways. B.The C3 convertase of the alternative pathway works as a soluble enzyme in the plasma. C.The C3 convertase of the alternative pathway cannot be inactivated by complement regulatory factors in the host. D.The C3 convertase of the alternative pathway is more efficiently recruited to pathogen surfaces than the C3 convertases of the classical and lectin pathways. E.The C3 convertase of the alternative pathway contains C3b, and can generate more of itself.
E. The C3 convertase of the alternative pathway contains C3b, and can generate more of itself
Multiple choice: The alternative pathway of complement activation has an important role in innate immunity, due to its ability to greatly amplify the amount of C3b deposited onto the pathogen surface. This amplification occurs because: A. The C3 convertase of the alternative pathway is much more active than those of the classical and lectin pathways. B. The C3 convertase of the alternative pathway works as a soluble enzyme in the plasma. C. The C3 convertase of the alternative pathway cannot be inactivated by complement regulatory factors in the host. D. The C3 convertase of the alternative pathway is more efficiently recruited to pathogen surfaces than the C3 convertases of the classical and lectin pathways. E. The C3 convertase of the alternative pathway contains C3b, and can generate more of itself.
E. The C3 convertase of the alternative pathway contains C3b, and can generate more of itself.
Multiple choice: One strategy for vaccine development currently under investigation is the use of pathogen-derived T cell epitopes as a component of the vaccine. For viral pathogens, implementing this strategy involves scanning the predicted amino acid sequences of the viral proteins for likely peptide epitopes that would bind to MHC class I and MHC class II molecules. In addition to the complication of MHC sequence polymorphism in the human population, another complication of this strategy for peptide epitopes that would bind to MHC class II proteins is: A. The importance of viral proteins containing peptides that are cleaved into 8-10 amino acid long fragments. B. The ability of viruses to mutate their proteins to avoid MHC anchor residue sequences. C. The fact that long peptides (>13 amino acids) are rapidly degraded in cells. D. The fact that MHC class II proteins are intrinsically stable, even in the absence of binding to a peptide. E. The absence of defined sequence motifs that predict peptide binding to MHC class II molecules.
E. The absence of defined sequence motifs that predict peptide binding to MHC class II molecules.
One strategy for vaccine development currently under investigation is the use of pathogen-derived T cell epitopes as a component of the vaccine. For viral pathogens, implementing this strategy involves scanning the predicted amino acid sequences of the viral proteins for likely peptide epitopes that would bind to MHC class I and MHC class II molecules. In addition to the complication of MHC sequence polymorphism in the human population, another complication of this strategy for peptide epitopes that would bind to MHC class II proteins is: A. The importance of viral proteins containing peptides that are cleaved into 8-10 amino acid long fragments. B. The ability of viruses to mutate their proteins to avoid MHC anchor residue sequences. C. The fact that long peptides (>13 amino acids) are rapidly degraded in cells. D. The fact that MHC class II proteins are intrinsically stable, even in the absence of binding to a peptide. E. The absence of defined sequence motifs that predict peptide binding to MHC class II molecules.
E. The absence of defined sequence motifs that predict peptide binding to MHC class II molecules.
Women with urinary tract infections caused by E. coli are generally treated with a course of antibiotics. A common complication of the antibiotic treatment is the occurrence of a vaginal yeast infection caused by Candida albicans, an organism that is normally present in very low numbers in the human vaginal tract. This complication occurs because: A. The E. coli infection damages the reproductive epithelium, causing a breach in the tight junctions and allowing invasion by the Candida albicans. B. The E. coli infection induces adhesion molecule expression on the reproductive epithelium, allowing attachment of the yeast. C. The antibiotic treatment kills all strains of fungi present in the reproductive tract, except the Candida albicans. D. The E. coli infection causes gastrointestinal distress leading to diarrhea. E. The antibiotics kill many of the commensal organisms in the reproductive tract, allowing overgrowth of the fungus.
E. The antibiotics kill many of the commensal organisms in the reproductive tract, allowing overgrowth of the fungus
Multiple choice: Women with urinary tract infections caused by E. coli are generally treated with a course of antibiotics. A common complication of the antibiotic treatment is the occurrence of a vaginal yeast infection caused by Candida albicans, an organism that is normally present in very low numbers in the human vaginal tract. This complication occurs because: A. The E. coli infection damages the reproductive epithelium, causing a breach in the tight junctions and allowing invasion by the Candida albicans. B. The E. coli infection induces adhesion molecule expression on the reproductive epithelium, allowing attachment of the yeast. C. The antibiotic treatment kills all strains of fungi present in the reproductive tract, except the Candida albicans. D. The E. coli infection causes gastrointestinal distress leading to diarrhea. E. The antibiotics kill many of the commensal organisms in the reproductive tract, allowing overgrowth of the fungus.
E. The antibiotics kill many of the commensal organisms in the reproductive tract, allowing overgrowth of the fungus.
Multiple choice: Women with urinary tract infections caused by E. coli are generally treated with a course of antibiotics. A common complication of the antibiotic treatment is the occurrence of a vaginal yeast infection caused by Candida albicans, an organism that is normally present in very low numbers in the human vaginal tract. This complication occurs because: A. The E. coli infection damages the reproductive epithelium, causing a breach in the tight junctions and allowing invasion by the Candida albicans. B. The E. coli infection induces adhesion molecule expression on the reproductive epithelium, allowing attachment of the yeast. C. The antibiotic treatment kills all strains of fungi present in the reproductive tract, except the Candida albicans. D. The E. coli infection causes gastrointestinal distress leading to diarrhea. E. The antibiotics kill many of the commensal organisms in the reproductive tract, allowing overgrowth of the fungus.
E. The antibiotics kill many of the commensal organisms in the reproductive tract, allowing overgrowth of the fungus.
Multiple choice: Macrophages express multiple types of receptors on their surface that stimulate phagocytosis of microbes, leading to pathogen internalization and destruction. Many of these receptors, such as Dectin-1, rely on direct recognition of a PAMP on the pathogen surface. However, some receptors that stimulate phagocytosis rely on soluble factors (not associated with the phagocyte membrane) to identify and mark the pathogen for uptake by the phagocyte. One such receptor is: A. The mannose receptor B. The class A scavenger receptor C. The lipid receptor D. The macrophage C-type lectin receptor E. The complement receptor
E. The complement receptor
Multiple choice: Individuals with defects in T cell development have a severe immunodeficiency disease called SCID (severe combined immunodeficiency disease). In these individuals, the absence of all T cells causes defects in both cell-mediated (T cell- based) and humoral (antibody-based) immune responses. The defect in antibody responses in SCID patients is due to: A. The important role of T cells in regulating B cell development in the bone marrow B. The inter-dependence of T cells and B cells for the normal development of secondary lymphoid organs. C. The absence of phagocytic cells needed for antibody-dependent pathogen clearance in SCID patients D. The poor survival of B cells in patients with defects in their T cells E. The important role of T follicular helper cells in generating protective antibody responses
E. The important role of T follicular helper cells in generating protective antibody responses
Individuals with defects in T cell development have a severe immunodeficiency disease called SCID (severe combined immunodeficiency disease). In these individuals, the absence of all T cells causes defects in both cell-mediated (T cell-based) and humoral (antibody-based) immune responses. The defect in antibody responses in SCID patients is due to: A. The important role of T cells in regulating B cell development in the bone marrow B. The inter-dependence of T cells and B cells for the normal development of secondary lymphoid organs. C. The absence of phagocytic cells needed for antibody-dependent pathogen clearance in SCID patients D. The poor survival of B cells in patients with defects in their T cells E. The important role of T follicular helper cells in generating protective antibody responses
E. The important role of T follicular helper cells in generating protective antibody responses.
Multiple choice: The terminal components of the complement pathway assemble to form a membrane attack complex that can induce pathogen lysis and death. Yet, evidence indicates that this feature of complement is less important than the earlier steps that promote pathogen opsonization and induce inflammation. This conclusion is based on: A. In vitro experiments showing that very few species of bacteria are susceptible to lysis by the membrane attack complex B. Experiments indicating that only bacteria, but not viruses or fungi, are susceptible to lysis by the membrane attack complex C. The very low levels of terminal complement components in the serum D. The fact that other mammalian species lack the terminal components of the complement pathway needed to form the membrane attack complex E. The limited susceptibility to infections of patients with deficiencies in terminal complement components
E. The limited susceptibility to infections of patients with deficiencies in terminal complement components
Multiple choice: The terminal components of the complement pathway assemble to form a membrane attack complex that can induce pathogen lysis and death. Yet, evidence indicates that this feature of complement is less important than the earlier steps that promote pathogen opsonization and induce inflammation. This conclusion is based on: A. In vitro experiments showing that very few species of bacteria are susceptible to lysis by the membrane attack complex B. Experiments indicating that only bacteria, but not viruses or fungi, are susceptible to lysis by the membrane attack complex C. The very low levels of terminal complement components in the serum D. The fact that other mammalian species lack the terminal components of the complement pathway needed to form the membrane attack complex E. The limited susceptibility to infections of patients with deficiencies in terminal complement components
E. The limited susceptibility to infections of patients with deficiencies in terminal complement components
The terminal components of the complement pathway assemble to form a membrane attack complex that can induce pathogen lysis and death. Yet, evidence indicates that this feature of complement is less important than the earlier steps that promote pathogen opsonization and induce inflammation. This conclusion is based on: A. In vitro experiments showing that very few species of bacteria are susceptible to lysis by the membrane attack complex B. Experiments indicating that only bacteria, but not viruses or fungi, are susceptible to lysis by the membrane attack complex C. The very low levels of terminal complement components in the serum D. The fact that other mammalian species lack the terminal components of the complement pathway needed to form the membrane attack complex E. The limited susceptibility to infections of patients with deficiencies in terminal complement components
E. The limited susceptibility to infections of patients with deficiencies in terminal complement components
Given the enormous heterogeneity of antigen receptors expressed on the populations of naive B and T lymphocytes, the adaptive immune response relies on a process whereby the rare lymphocyte that binds to the antigen is first induced to proliferate, before it can perform its effector function. For B cells, there is a clever mechanism that ensures that the specificity of the antibody secreted by the plasma cell will recognize the same pathogen that initially stimulated the B cell antigen receptor and induced B cell proliferation. This mechanism is: A. The naive B cell expresses an array of different B cell antigen receptors, and randomly chooses which specificity of antibody to secrete as a plasma cell. B. The naive B cell expresses a single specificity of B cell antigen receptor, and then up-regulates the expression of this receptor so it can bind tightly to the pathogen. C. The plasma cell proliferates after it has finished secreting antibody to generate more plasma cells with specificity for the pathogen. D. The plasma cell traps secreted antibody molecules in its extracellular matrix and uses these antibodies to bind to the pathogen. E. The naive B cell expresses a membrane-bound form of the antibody as a receptor, and secretes that same antibody when it differentiates into a plasma cell.
E. The naive B cell expresses a membrane-bound form of the antibody as a receptor, and secretes that same antibody when it differentiates into a plasma cell.
Multiple choice: Given the enormous heterogeneity of antigen receptors expressed on the populations of naive B and T lymphocytes, the adaptive immune response relies on a process whereby the rare lymphocyte that binds to the antigen is first induced to proliferate, before it can perform its effector function. For B cells, there is a clever mechanism that ensures that the specificity of the antibody secreted by the plasma cell will recognize the same pathogen that initially stimulated the B cell antigen receptor and induced B cell proliferation. This mechanism is: A. The naive B cell expresses an array of different B cell antigen receptors, and randomly chooses which specificity of antibody to secrete as a plasma cell. B. The naive B cell expresses a single specificity of B cell antigen receptor, and then up-regulates the expression of this receptor so it can bind tightly to the pathogen. C. The plasma cell proliferates after it has finished secreting antibody to generate more plasma cells with specificity for the pathogen. D. The plasma cell traps secreted antibody molecules in its extracellular matrix and uses these antibodies to bind to the pathogen. E. The naive B cell expresses a membrane-bound form of the antibody as a receptor, and secretes that same antibody when it differentiates into a plasma cell.
E. The naive B cells expresses a membrane-bound form of the antibody as a receptor, and secretes that same antibody when it differentiates into a plasma cell.
During MHC class I synthesis and folding in the ER, the newly synthesized MHC class I protein is held in a peptide receptive state by binding to the calreticulin:ERp57:tapasin complex. Some peptides undergo peptide editing, which is dependent on
ERAP
Amino acid sequence analysis of all of the peptides found in a single IgG antibody would reveal unique peptide sequences totaling ~600-700 amino acids. Using this estimate, the predicted molecular weight of an antibody protein would be ~70-75 kDa. Yet, an intact antibody protein has a molecular weight of ~150 kDa. The explanation for this discrepancy is
Each IgG antibody is a complex of two identical light chains and two identical heavy chains.
Many different NOD-like receptors, including several with pyrin domains and several with HIN domains, can function to trigger inflammasome assembly leading to the activation of caspase-1. The reason for many different sensors in this innate response system is that:
Each NOD-like receptor recognizes different PAMPs and is activated by different pathogens.
NK cells express receptors from several families, each of which has multiple members. Some of these receptors are activating and others are inhibitory, and NK cell activation is dependent on the balance of signaling overall. The individual NK cells in an individual:
Each express only a subset of all possible NK receptors
The production of antimicrobial peptides is one of the most evolutionarily ancient mechanisms of defense for multicellular organisms, and most eukaryotic species make many different forms of these proteins. For instance, human paneth cells in the gastrointestinal epithelium make 21 different defensins. The reason for this diversity of antimicrobial peptides is:
Each one has distinct activities against Gram-negative bacteria, Gram-positive bacteria, or fungi.
Who is the father of immunology?
Edward Jenner
Which of the following is MOST likely to simulate/activate a memory T cell?
Either a B cell, dendritic cell, or a macrophage
Herpes viruses are a class of viruses that establish life-long infections in human hosts. Estimates suggest that >90% of the population is infected with several of these viruses, including EBV, CMV, and herpes zoster, the cause of chicken pox. One herpes virus, Herpes Simplex virus, causes recurrent cold sores in infected individuals. Thus, in spite of a robust anti-viral CD8 T cell response, these individuals still suffer from periodic virus-induced cold sores following exposure to UV light or certain hormones or other stressors. This anti-viral CD8 T cell response:
Eliminates infected epithelial cells but not infected neurons
Herpesviruses are a class of viruses that establish life-long infections in human hosts. One herpesvirus, Herpes Simplex virus, causes recurrent cold sores in infected individuals. Thus, in spite of a robust anti-viral CD8 T cell response, these individuals still suffer from periodic virus-induced cold sores following exposure to UV light or certain hormones or other stressors. This anti-viral CD8 T cell response:
Eliminates infected epithelial cells but not infected neurons
In patients with lymphomas, the cancer cells invade the bone marrow and destroy the environment required for normal hematopoiesis. This leads to bone marrow failure, which disrupts the production of hematopoietic cell lineages. All of the following cell types would be affected by this EXCEPT:
Endothelial cells
Even when the complement cascade fails to proceed beyond generating the C3 convertase, complement activation is effective at inducing pathogen uptake and destruction. This process of immune protection is mediated by:
Engagement of complement receptors on phagocytes by C3b and its cleavage products which promotes phagocytosis
Even when the complement cascade fails to proceed beyond generating the C3 convertase, complement activation is effective at inducing pathogen uptake and destruction. This process of immune protection is mediated by:
Engagement of complement receptors on phagocytes by C3b which promotes phagocytosis
The thymic cortex has a substantial population of macrophages in addition to the developing T cells (i.e., thymocytes). These macrophages are extremely useful because they:
Engulf apoptotic thymocytes
While CD28 co-stimulation is important for the initial activation of naive T cells, other co-stimulatory molecules function at later stages of the T cell response. Several of these other co-stimulatory molecules are members of the TNF-receptor family, and function by activating the transcription factor, NFkB. Therefore, stimulation of these co-stimulatory TNF-receptors on activated T cells is likely to:
Enhance T cell survival
At early timepoints following an infection, examination of lymph node CD4 T cells responding to the pathogen would show a heterogeneous population of cells representing several different effector lineages. Likewise, the cytokines produced by these cells would include IFN-gamma, IL-4, and possibly others. However, approximately one week later at the peak of the T cell response, the pathogen-specific CD4 T cell population would be largely homogeneous in their production of a single effector subset cytokine profile. This change comes about due to:
Enhanced differentiation of newly activated CD4 T cells into one effector subset
One striking feature of TCR interactions with peptide:MHC complexes is that amino acid residues in the MHC protein are as important to the TCR binding strength as are amino acid residues in the pathogen-derived peptide. This feature is in contrast to antigen recognition by antibodies, which is a direct interaction that is independent of other host proteins. Based on the different functions of T cells versus antibodies in the adaptive immune response, the fact that TCRs recognize components of both the MHC and the bound peptide exists to:
Ensure that TCRs are focused on recognizing antigens associated with host cells, and not those that are free in solution
How are epithelia protected from pathogens?
Epithelia are also protected by many kinds of chemical defenses, including antimicrobial enzymes and peptides.
What are the two chemical defenses that are protected by the Epithelia?
Epithelia are protected by many kinds of chemical defenses, including: 1. antimicrobial enzymes 2. antimicrobial peptides.
What is the EPITHELIA comprised of?
Epithelia comprise the skin and the linings of the body's tubular structures— the respiratory, urogenital, and gastrointestinal tracts.
What does Epithelia consist of?
Epithelia consists of the skin and the linings of the body's tubular structures Ex. The respiratory, urogenital, and gastrointestinal tracts.
Where do antimicrobial peptides come from?
Epithelial cells secrete these antimicrobial peptides into the fluids bathing the mucosal surface, whereas phagocytes secrete them in tissues.
How are Antimicrobial Peptides secreted?
Epithelial cells secrete these peptides into the fluids bathing the mucosal surface, whereas phagocytes secrete them in tissues.
NK cells do not express TCR molecules, yet they bind to class I MHC molecules on potential target cells. Explain how NK cells lacking TCRs can specifically recognize infected cells and tumor cells
Even though Natural Killer cells do not have TCRs, they bind to class 1 MHC molecules to determine whether or not to kill. In a normal self-cell, the cell will have MHC class 1 represented on its surface. When a NK cell comes up to the self-cell, the MHC class 1 binds to an inhibitory receptor on the NK cell, preventing the NK cell from killing the self cell. When a self-cell has been infected, it will not express that MHC class 1 molecule on the surface. This lack of a MHC class 1 will leave the inhibitory receptor on the NK cell with nothing to bind to. This means that the NK cell will not be inhibited, and it will kill off the infected and tumor cells.
Effector memory T cells can be distinguished from central memory T cells by:
Expression of CCR7
Which of the following options correctly describes a difference between the B-cell receptor and the T -cell receptor?
Expression of the B-cell receptor stops further light chain rearrangement and enforces strict allelic exclusion, while expression of the T-cell receptor does not restrict further rearrangements of the alpha chain until there is signaling through peptide:MHC binding, resulting in many T cells that express two different TCRα chains.
Which of the following options correctly describes a difference between the B-cell receptor and the T-cell receptor?
Expression of the B-cell receptor stops further light chain rearrangement and enforces strict allelic exclusion, while expression of the T-cell receptor does not restrict further rearrangements of the alpha chain until there is signaling through peptide:MHC binding, resulting in many T cells that express two different TCRα chains.
Empty MHC class I and MHC class II molecules are rapidly removed from the cell surface. This process prevents:
Extracellular peptides from binding these MHC molecules, as these peptides could be recognized by T cells leading to inappropriate T cell activation
Initially after an infection, the majority of the T cells present in the tissue at a site of infection are not specific for the infecting pathogen, but over the course of several days, this changes and antigen-specific T cells become enriched at this site. This is because:
Extravasation from blood into tissues is determined by homing molecules, not antigen specificity. NOTE: Yes. In the early stage of the adaptive immune response, only a minority of the effector T cells that enter infected tissues will be specific for pathogen. This is because activation of the endothelium of local blood vessels by inflammatory cytokines induces expression of selectins, integrin ligands, and chemokines that can recruit any circulating effector or memory T cell that expresses the appropriate trafficking receptors, irrespective of its antigenic specificity. However, specificity of the reaction is rapidly increased as the number of pathogen- specific T cells increases and recognition of antigen within the inflamed tissue retains them there.
Fewer type III species reach maturity than type I mainly due to differences in:
Extrinsic mortality
Antigen can only come into lymph node if it is associated with an antigen-presenting cell
FALSE
Chemokines are chemoattractants for lymphocytes but not other leukocytes.
FALSE
True/False: Chemokines are small chemoattractant molecules made by epithelial cells, tissue macrophages, and endothelial cells in response to infection or injury. They differ slightly in sequence and structure based on the cells that secrete them, but all of them act to recruit both monocytes and neutrophils from the blood.
FALSE
True/False: In the sea urchin, a massive diversification of innate recognition receptors has occurred, resulting in the presence of over 200 TLR genes, over 200 NOD-like receptor genes, and over 200 scavenger receptor genes in the genome of these organisms. These receptors are unlikely to contribute to an enhanced innate immune response in sea urchins, because nearly all of these genes are pseuodgenes.
FALSE
True/False: All mammalian TLRs have been shown to directly bind to microbial products, leading to TLR signaling.
FALSE
True/False: Mucosal surfaces and external epithelia are major routes of pathogenic infection. Mucosal surfaces are found in tissues such as the gastrointestinal tract, the reproductive tract and the mouth and respiratory tract. While the mouth and respiratory tract are routes of virus but not bacterial infections, the gastrointestinal tract is the route for bacterial but not virus infections.
FALSE
True/False: Our immune system efficiently kills all categories of microbes that attempt to colonize our bodies.
FALSE
True/False: The C3 convertase amplifies the process of complement activation by generating large amounts of C3b and cleaving large numbers of C5 molecules.
FALSE
True/False: The acute phase response contributes to infection control by producing molecules that promote pathogen opsonization and complement activation. This response is only induced by direct action of microbial components on hepatocytes in the liver.
FALSE
True/False: The classical and lectin pathways of complement activation converge at the step of C3 activation. However, the initiating steps of each pathway use protein components and enzymatic mechanisms that share no similarity with each other.
FALSE
In a lymph node, nTreg cells are able to inhibit the responses of other T cells in their vicinity. This inhibition is specific, as the nTreg cell and the naive T cell must share the same antigen specificity.
FALSE NOTE: nTreg cells in a lymph node function primarily by acting on antigen-presenting cells to down-regulate their co-stimulatory activity and their inflammatory cytokine production. Based on this mechanism, it is not necessary that the nTreg cell and the naive T cell whose response is inhibited share the same antigen specificity.
Which of the following acts as a protease that is required to generate the alternative pathway C3 convertase
Factor D
What does FACTOR H bind to?
Factor H binds preferentially to C3b bound to vertebrate cells because it has an affinity for the sialic acid residues present on their cell surfaces (see Fig. 2.18). Thus, the amplification loop of the alternative pathway is allowed to proceed on the surface of a pathogen or on damaged host cells, but not on normal host cells or on tissues that express these negative regulatory proteins
What is FACTOR H?
Factor H is another complement-regulatory protein in plasma that binds C3b. Like CR1, it is able to compete with factor B to displace Bb from the convertase In addition, it acts as a cofactor for factor I.
All mammalian TLRs have been shown to directly bind to microbial products, leading to TLR signaling.
False
C3a and C3b are fragments of C3 that are generated by proteolytic cleavage mediated by two different enzyme complexes. (true or false)
False
Mucosal surfaces and external epithelia are major routes of pathogenic infection. Mucosal surfaces are found in tissues such as the gastrointestinal tract, the reproductive tract and the mouth and respiratory tract. White the mouth and respiratory tract are routes of virus by not bacterial infections, the gastrointestinal tract is the route for bacterial but not virus infections.
False
Mucosal surfaces and external epithelia are major routes of pathogenic infection. Mucosal surfaces are found in tissues such as the gastrointestinal tract. While the mouth and respiratory tract are routes of virus but not bacterial infections, the gastrointestinal tract is the route for bacterial but not virus infections.
False
Our immune system efficiently kills all categories of microbes that attempt to colonize our bodies.
False
T or F: All cell surface Fc receptors bind antibodies with low affinities. In the absence of antigens, antibodies do not associate with cell surface Fc receptors.
False
T or F: All cell surface Fc receptors bind the Fc regions of antibodies with low affinity. In the absence of antigen crosslinking, no antibody associates with cell surface Fc receptors.
False
T or F: CTLA-4 and PD-1 are both inhibitors of T cell activation but their mechanisms are different. CTLA-4 recruits protein phosphatase SHP to de-phosphorylate ITAMs, while PD-1 sequesters B7 molecules from CD28.
False
T or F: Cell surface expression of MHC class I depends on an abundant source of pathogen-derived peptides. Thus, in uninfected cells, nearly all of the MHC class I proteins are degraded and never reach the cell surface.
False
T or F: Diacylglycerol (DAG) is one of the two products generated when PLC-gamma cleaves the membrane phospholipid, PIP2. This small lipid mediator remains associated with the plasma membrane and induce calcium entry into the cell.
False
T or F: During B cell development, pre-B-cell receptors receive signals from self-antigens for the lymphocytes to survive and proliferate.
False
T or F: If the donor HLA haplotype matches that of the recipient's, there will be no rejection to the transplanted organ, even without immunosuppression treatment.
False
T or F: One form of SCID is DiGeorge syndrome(DGS), in which the thymic epithelium fails to develop normally. Without the proper inducive thymic environment, T cells cannot mature, and both cell-mediated immunity and T-cell-dependent antibody production are impaired. However, if infants diagnosed with DGS receive bone marrow transplants (hematopoietic stem cells) from healthy donors, their T-cell-dependent immunity will be restored.
False
T or F: The acute phase response contributes to infection control by producing molecules that promote pathogen opsonization and complement activation. This response is only induced by direct action of microbial components on hepatocytes in the liver.
False
T or F: The classical and lectin pathways of complement activation converge at the step of C3 activation. However, the initiating steps of each pathway use protein components and enzymatic mechanisms that share NO similarity with each other.
False
T or F: The generation of a complete coding sequence for an antibody heavy chain involves a process of DNA rearrangement that links V, D, and J gene segments together to form the exon that encodes the heavy chain V region. A similar type of DNA rearrangement is also utilized for the simultaneous expression of IgM and IgD antibodies by the same B cell.
False
T or F: The mechanism by which CTLA-4 and PD-1 inhibit T cell activation is by recruiting inhibitory phosphatase SHP and SHIP to remove the phosphates from ITAMs.
False
T or F: The population of HIV viral variants circulating in the human population is extremely diverse, a phenomenon that contributes to the difficulties in generating an HIV vaccine. However, within a given individual, all HIV viruses are genetically identical.
False
T-cells kill infected host cells through the activation of caspases and the recruitment of natural killer cells.
False
T/F: All allergic reactions are mediated by IgE.
False
T/F: Common variable immunodeficiency (CVID) severely impairs both T-cell and antibody responses.
False
T/F: If the donor HLA haplotype matches that of the recipient's, there will be no rejection to the transplanted organ, even without immunosuppression treatment.
False
T/F: Inflammatory bowel disease- Crohn's disease and ulcerative colitis- is a disease in which the adaptive immune system causes tissue damage in response to self antigens originated from human tissues.
False
T/F: One form of SCID is DiGeorge syndrome, in which the thymic epithelium fails to develop normally. Without the proper inducive thymic evironment, T cells cannot mature, and both cell-mediated immunity and T-cell-dependent antibody production are impaired. However, if infants diagnosed with DGS receive bone marrow transplants (hematopoietic stem cells) from healthy donors, their T-cell-dependent immunity will be restored.
False
T/F: The immune response is a dynamic process that initiates with an antigen-independent response, which becomes more focused and powerful as it develops antigen specificity. Once the adaptive immune system develops, a single type of cell or immunoglobulin is capable of eliminating any type of pathogens.
False
T/F: The immune system efficiently kills all categories of microbes that attempt to colonize our bodies.
False
T/F: The population of HIV viral variants circulating in the human population is extremely diverse, a phenomenon that contributes to the difficulties in generating an HIV vaccine. However, within a given individual, all HIV viruses are genetically identical.
False
The antibody protein has two functional domains, one for antigen binding and a second to confer specific effector functions. These two functional domains are encoded by the antibody light chain and antibody heavy chain polypeptides, respectively.
False
The classical and lectin pathways of complement activation converge at the step of C3 activation. However, the initiating steps of each pathway use protein components and enzymatic mechanisms that share no similarity with each other
False
The enzymes that cleave C3 and C4 are referred to as convertases (true or false)
False
True or False: Macrophages, neutrophils, and dendritic cells (DCs) are all phagocytes. Because of this, they can present pathogen-derived protein antigens to T cells. In this regard, they are antigen-presenting cells (APCs) as well.
False
True or False: T-cell receptor structure is much simpler than B-cell receptor. TCR mimics the Fab region in a BCR. Therefore, TCR is completely made up of variable regions, unlike BCRs which have both variable and constant regions.
False
True or False: The antibody protein has two functional domains, one for antigen binding, and a second to confer specific effector functions. The former is encoded by the light chain and the latter the heavy chain.
False
True or False: Mucosal surfaces and external epithelia are major routes of pathogenic infection. Mucosal surfaces are found in tissues such as the gastrointestinal tract, the reproductive tract and the mouth and respiratory tract. While the mouth and respiratory tract are routes of virus but not bacterial infections, the gastrointestinal tract is the route for bacterial but not virus infections.
False
True or False: The C3 convertase amplifies the process of complement activation by generating large amounts of C3b and cleaving large numbers of C5 molecules.
False
True or False: The classical and lectin pathways of complement activation converge at the step of C3 activation. However, the initiating steps of each pathway use protein components and enzymatic mechanisms that share NO similarity with each other.
False
True/False: All mammalian TLRs have been shown to directly bind to microbial products, leading to TLR signaling.
False
True/False: Alloreactivity refers to the ability of T cells to respond to allelic polymorphisms in MHC molecules when mixed with antigen-presenting cells from a genetically different individual. The T-cell receptors involved in alloreactive responses are recognizing amino acid sequences on foreign MHC molecules and do not interact at all with the peptides bound to these MHC molecules.
False
True/False: Chemokines are small chemoattractant molecules made by epithelial cells, tissue macrophages, and endothelial cells in response to infection or injury. They differ slightly in sequence and structure based on the cells that secrete them, but all of them act to recruit both monocytes and neutrophils from the blood.
False
True/False: In the sea urchin, a massive diversification of innate recognition receptors has occurred, resulting in the presence of over 200 TLR genes, over 200 NOD-like receptor genes, and over 200 scavenger receptor genes in the genome of these organisms. These receptors are unlikely to contribute to an enhanced innate immune response in sea urchins, because nearly all of these genes are pseuodgenes.
False
True/False: Like innate sensors of infections (TLRs, NLRs, RLRs), antibodies frequently recognize nucleic acids of pathogenic organisms.
False
True/False: MHC class I surface expression is dependent on an abundant source of pathogen-derived peptides. Thus, in uninfected cells, nearly all of the MHC class I proteins are degraded and never reach the cell surface.
False
True/False: Most eukaryotic genes are encoded in a set of exons that are brought together to form a contiguous protein coding sequence by the process of mRNA splicing. In contrast, immunoglobulin genes use somatic recombination of gene segments and not mRNA splicing to generate the final mRNA that is translated into protein.
False
True/False: Mucosal surfaces and external epithelia are major routes of pathogenic infection. Mucosal surfaces are found in tissues such as the gastrointestinal tract, the reproductive tract and the mouth and respiratory tract. While the mouth and respiratory tract are routes of virus but not bacterial infections, the gastrointestinal tract is the route for bacterial but not virus infections.
False
True/False: Our immune system efficiently kills all categories of microbes that attempt to colonize our bodies.
False
True/False: The C3 convertase amplifies the process of complement activation by generating large amounts of C3b and cleaving large numbers of C5 molecules.
False
True/False: The acute phase response contributes to infection control by producing molecules that promote pathogen opsonization and complement activation. This response is only induced by direct action of microbial components on hepatocytes in the liver.
False
The C3 convertase amplifies the process of complement activation by generating large amounts of C3b and cleaving large numbers of C5 molecules.
False The C3 convertase does generate large numbers of C3b molecules which become attached to the pathogen surface in the vicinity of the convertase. This enzyme can only cleave C5 when bound to a molecule of C3b, generating the C5 convertase. The generation of the C5 convertase occurs at a much lower level than the C3 convertase, and many fewer molecules of C5 than C3 are cleaved.
True/False: Chemokines are small chemoattractant molecules made by epithelial cells, tissue macrophages, and endothelial cells in response to infection or injury. They differ slightly in sequence and structure based on the cells that secrete them, but all of them act to recruit both monocytes and neutrophils from the blood.
False. Chemokines encompass a large family of molecules that are structurally related. The different chemokines are made by distinct cell types and also act as chemoattractants for different cell types. The differences generally result from differential expression of specific chemokine receptors on different cell types. For instance the receptor for CXCL8 is expressed on neutrophils, but not on monocytes; thus, CXCL8 is a chemoattractant for neutrophils but not monocytes
True/False: All mammalian TLRs have been shown to directly bind to microbial products, leading to TLR signaling.
False. Some TLRs have been shown to make direct contact with microbial ligands based on X-ray crystal structures. However, this has not been confirmed for all TLRs. The Drosophila receptor Toll does not recognize microbial products directly, but instead, recognizes a cleaved product of a self-protein, Spätzle. This leaves open the possibility that some mammalian TLRs may function similarly to Drosophila Toll. Furthermore, TLR4 requires an accessory protein, MD-2 for binding to LPS.
True/False: The acute phase response contributes to infection control by producing molecules that promote pathogen opsonization and complement activation. This response is only induced by direct action of microbial components on hepatocytes in the liver.
False. The acute phase is induced by inflammatory cytokines (TNF-α, IL-1β, IL-6) produced by the host in response to infection. These cytokines act on hepatocytes to produce a variety of proteins, including C-reactive protein, MBL, surfactant proteins, and fibrinogen. Many of these proteins bind pathogens, but not host cells, and contribute to pathogen clearance by promoting phagocytosis and complement activation
True/False: In the sea urchin, a massive diversification of innate recognition receptors has occurred, resulting in the presence of over 200 TLR genes, over 200 NOD-like receptor genes, and over 200 scavenger receptor genes in the genome of these organisms. These receptors are unlikely to contribute to an enhanced innate immune response in sea urchins, because nearly all of these genes are pseuodgenes.
False. While some of these genes are pseudogenes, the majority encode functional proteins. It is likely that these genes have undergone rapid evolution, indicating a rapid change in receptor specificities, perhaps in response to microbial evolution and/or immune evasion. The properties of the LRR domains are consistent with the idea that these receptors represent a highly diversified pathogen recognition system.
True/False: Mucosal surfaces and external epithelia are major routes of pathogenic infection. Mucosal surfaces are found in tissues such as the gastrointestinal tract, the reproductive tract and the mouth and respiratory tract. While the mouth and respiratory tract are routes of virus but not bacterial infections, the gastrointestinal tract is the route for bacterial but not virus infections.
False. Both bacterial and virus infections can use both the mouth and respiratory tract and the gastrointestinal tract. There is no route of infection that is specific for a single category of pathogen.
True/False: The C3 convertase amplifies the process of complement activation by generating large amounts of C3b and cleaving large numbers of C5 molecules.
False. The C3 convertase does generate large numbers of C3b molecules which become attached to the pathogen surface in the vicinity of the convertase. This enzyme can only cleave C5 when bound to a molecule of C3b, generating the C5 convertase. The generation of the C5 convertase occurs at a much lower level than the C3 convertase, and many fewer molecules of C5 than C3 are cleaved.
True/False: The classical and lectin pathways of complement activation converge at the step of C3 activation. However, the initiating steps of each pathway use protein components and enzymatic mechanisms that share no similarity with each other.
False. The initiating steps of the classical and lectin pathways of complement activation are remarkably conserved in their mechanisms. The pathogen recognition component of the classical pathway, C1q, has structural similarity to MBL and the ficolins. The C1r and C1s components of the classical pathway, that are activated to form the serine protease, are closely related to the MASP proteins of the lectin pathway.
True/False: Chemokines are small chemoattractant molecules made by epithelial cells, tissue macrophages, and endothelial cells in response to infection or injury. They differ slightly in sequence and structure based on the cells that secrete them, but all of them act to recruit both monocytes and neutrophils from the blood.
False. Cell specific.
ALPS
Fas
A few days after virus infection is cleared, the majority of virus-specific CD8 T cells start to die. Death of these T cells is caused by
Fas-induced apoptosis
A few days after virus infection is cleared, the majority of virus-specific CD8 T cells starts to die. Death of these T cells is caused by
Fas-induced apoptosis
The kinetics of a typical CD8 T cell response to an acute virus infection in mice is shown in the figure below. In this example, the virus is cleared by ~day 7 post-infection, and starting at ~day 10 post-infection, the majority of the virus-specific CD8 T cells die. The death of these virus-specific CD8 T cells is caused by:
Fas-induced death or cytokine withdrawal NOTE: Yes. When an infection is effectively repelled by the adaptive immune system, most effector T cells undergo 'death by neglect,' removing themselves by apoptosis. The resulting 'clonal contraction' of effector T cells appears to be due both to the loss of pro-survival cytokines that are produced by antigenic stimulation, such as IL-2, and to the loss of expression of receptors for these cytokines. While many effector T cells die from the loss of survival signals and the activation of the Bim-mediated intrinsic pathway of apoptosis, effector T cell death can also occur via the extrinsic pathway of apoptosis that is activated by signaling via members of the TNF receptor superfamily, particularly Fas (CD95).
Are there more MANNOSE-BINDING LECTIN (MBL) or FICOLIN in plasma?
Ficolins are more abundant than MBL in plasma and so may be more important in practice
Our environment contains masses of microorganisms, many of which reside as commensal organisms on our body's mucosal and epithelial surfaces without causing disease. What two features distinguish a pathogenic microbe from these commensal microbes?
First, a pathogenic microbe must establish a replicating colony of organisms inside our body. This occurs by pathogens crossing epithelial barriers and replicating in tissue, or by attaching to the epithelial surface and establishing a colony there. The second feature is that the pathogen needs to have special mechanisms to evade the innate immune response.
Studies have shown that secondary lymphoid tissues are a major reservoir of HIV in infected individuals. In part, this is due to the high numbers of viral target cells expressing CD4, such as T cells, macrophages, and dendritic cells. Surprisingly, secondary lymphoid tissues were also found to contain large numbers of infectious virus particles in the form of immune complexes. A comparison of the viral species found in these immune complexes indicates that they include virus particles that have been retained for over a year. The cells responsible for this reservoir of infectious HIV are:
Follicular dendritic cells
Which of the following is NOT an essential roll of inflammation?
Form a complex at the site of infection for the reactivation of memory cells
IPEX
FoxP3
Effector caspases are activated downstream of both extrinsic and intrinsic pathways of apoptosis. Consequently, cells lacking one or more of these enzymes show defects in apoptosis. An alternative means of eliminating the activity of an effector caspase would be to:
Generate a form of the pro-caspase with a mutation in the initiator caspase cleavage site. NOTE: Yes. If this cleavage site is mutated, the caspase could not be activated.
Inflammation has three essential roles in combating infection. Which of the following is NOT one of its three roles?
Generate immunological memory, so that response to a second exposure would be enhanced
A common misconception is that our immune system fails to make a productive immune response to HIV infection, thereby leading to chronic infection. Following a primary HIV infection, our immune system:
Generates a response that efficiently controls viral replication
A common misconception is that our immune system fails to make a productive immune response to HIV infection, thereby leading to chronic infection. In fact, following a primary HIV infection, our immune system:
Generates a response that efficiently controls viral replication
Which one is NOT an autoantigen in systemic lupus erythematosus?
Gluten
Define Glycosidase.
Glycosidase is an enzyme that catalyzes the hydrolysis of a bond joining a sugar of a glycoside to an alcohol or another sugar unit
Match the following cell types with their specialized functions: Secretion of large amount of mucus
Goblet cells
Secretion of large amounts of mucus
Goblet cells
NK mediated killing:
Granule dependent killing involving granzyme and *perforin*. *Death receptor* dependent killing following binding of Fas-L/Fas receptor.
The first drug treatment for HIV liscensed in the US was zidovudine (AZT), a reverse transcriptase inhibitor. However, AZT has now been completely replaced by HAART as the recommended treatment for HIV-infected individuals. The use of HAART, rather than AZT, is preferred because:
HARRT is a combination therapy that reduces the possibility of viral escape mutants
Naive T cells leave the thymus and enter secondary lymphoid tissues via__________. Upon activation, the cell leaves the secondary lymphoid tissue via _______________.
HEVs, efferent lymphatics
Which of the following statements about human immunodeficiency virus (HIV) is correct?
HIV infects cells expressing CD4
What are the specialized cell type involved in the entry of lymphocytes into lymph nodes called?
High endothelial venule (HEV) cells
Which of the following options correctly describes a mechanism used to prevent fetal rejection?
High expression of HLA-G by the trophoblast
Which of the following options INCORRECTLY describes a mechanism used to prevent fetal rejection?
High levels of MCH class I and class II expression by the trophoblast
What are the specialized cell type involved in the entry of lymphocytes into lymph nodes called?
High-walled endothelium venules (HEV) cells
CTLs mediate a powerful and lethal immune response to infected host cells. Which of the following steps is NOT involved with CTL activation and function?
Histamine is released from cytoplasmic granules recruiting macrophages to the site of infection.
where are antimicrobial peptides called HISTATINS made? (3 places)
Histatins are constitutively produced in the oral cavity by the parotid, sublingual, and submandibular glands.
Antibodies are found in plasma- the fluid component of blood- and in extracellular fluids. This type of immunity is known as:
Humoral immunity
Match the primary immunodeficiency diseases with the defective mechanism: Omenn syndrome
Hypomorphic mutations in RAG1 or RAG2
MHC class ____ molecules are generated in the cytosol by _____.
I Proteasomes
Match the T cell integrin proteins to their binding partners on endothelial cells: LFA-1
ICAM-1
In the case of intracellular bacteria or protozoan infections, tissue-resident dendritic cells and macrophages stimulate ILC cells to produce a cytokine:
IFN gamma
Toxoplasma gondii is a single-celled parasitic protozoan that infects and replicates in macrophages. It is common in the environment, and is transmitted to humans by the ingestion of undercooked meat or by accidental ingestion of the parasite's oocytes from contaminated water or cat litter. Infected individuals with healthy immune systems are generally asymptomatic, and rapidly clear the infection. However, in AIDS patients, infections of Toxoplasma gondii can lead to severe disease and even death. To investigate the immune mechanisms important in controlling Toxoplasma gondii, a mouse model of the infection was developed. Mice were infected with the protozoa at a dose where the majority of the mice survive the infection, and at the same time, were injected with a neutralizing antibody to a cytokine made by T cells (anti-'X' IgG). A second group of mice received the protozoa plus a control IgG antibody, as shown in the figure. Based on this information, the most likely candidate for cytokine 'X' is:
IFN-gamma
Salmonella typhimurium is a Gram-negative bacterial pathogen that infects its host via the gastrointestinal (GI) tract. Early in infection, the bacteria enter and replicate in gut epithelial cells, where the infection induces the development of TH17 cells in the GI tract. However, this response does not eradicate the pathogen, as S. typhimurium has evolved strategies to evade the TH17 response and to spread systemically by infecting and replicating in macrophages. Therefore, a second phase of the immune response is required to completely eliminate the pathogen from the body, as has been demonstrated in mouse models of S. typhimurium infection. These experiments in mouse models likely showed that:
IFN-gamma is required to clear S. typhimurium from the body.
Phosphorylate IkappaB
IKK
Following an acute virus infection in which the host clears the virus by approximately one week post-infection, a population of virus-specific memory CD8 T cells is maintained and can be detected for months to years post-infection. In mice with a knockout of a single cytokine, however, virus-specific memory CD8 T cells cannot be maintained and disappear over time as shown in the figure below. Base on this information, the most likely identity of the cytokine that is missing in these knockout mice is _____________.
IL-15 NOTE: Yes. The homeostatic mechanisms governing the survival of memory T cells differ from those for naive T cells. Memory T cells divide more frequently than naive T cells, and their expansion is controlled by a shift in the balance between proliferation and cell death. The survival of memory T cells requires signaling by the receptors for the cytokines IL-7 and IL-15. IL-7 is required for the survival of both CD4 and CD8 memory T cells. In addition, IL-15 is critical for the long-term survival and proliferation of CD8 memory T cells under normal conditions. In the absence of IL-15 (or the IL-15R), memory CD8 T cells slowly disappear from the population.
The NLRP3 inflammasome leads to the release of:
IL-1beta
T-cell activation requires antigen being displayed in the context of an APC and interaction between co-stimulatory molecules on the APC and the T cell. In addition to these two signals, T-cell activity is often influenced by cytokines. Which of the following is an example of how cytokines can influence T-cell activity in the presence of MHC presentation and co-stimulatory ligand interaction?
IL-2 triggers T-cell proliferation
T-cell activation requires antigen being displayed in the context of an APC and interaction between co-stimulatory molecules on the APC and the T cell. In addition to these two signals, T-cell activity is often influenced by cytokines. Which of the following is an example of how cytokines can influence T-cell activity in the presence of MHC presentation and co-stimulatory ligand interaction?
IL-2 triggers T-cell proliferation.
In the case of extracellular bacterial infections, ILC3 is activated by tissue-resident dendritic cells and macrophages to produce the cytokine:
IL-22
Among the cytokines below, which one is most involved in defense against multicellular helminths?
IL-4
Which of the following cytokines is important to maintain T cell memory?
IL-7
Which of the following cytokines is important to maintain T-cell memory?
IL-7
Which of the following autoimmune disease is caused by mutations in a single gene?
IPEX (immune dysregulation, polyendocrinopathy, enteropathy, X-linked) syndrome
The TCR and BCR are each composed of two modules, an antigen-binding module and a signaling module; furthermore, in each case, the two functional modules are encoded by distinct polypeptides. In addition, the tyrosine kinases that initiate antigen receptor signaling are also separate proteins from those of each receptor. This is a different strategy for receptor signaling than the case of receptor tyrosine kinases, where the enzyme is an intrinsic component of the ligand-binding receptor protein. Name one advantage of this organization of the TCR and BCR that accounts for the expression of ZAP-70 and Syk, as well as ITAM-containing immunoreceptors, in many different subsets of immune cells.
ITAM-containing signaling subunits and enzymes are present as separate polypeptides and can be re-used by other immune cells to mediate signaling via distinct ligand-binding receptors. Fc receptors on NK cells can use the TCR chain as a signaling subunit and ZAP-70 as an enzyme. Neutrophils use ITAM-containing subunits DAP-12 or Fcr-y to activate Syk downstream of the PSGL-1 (P-selectin binding) receptor.
Portions of the cytoplasmic domains of many immune receptors are required for receptor activation. These domains are known as
ITAMs
MHC genes are the most polymorphic genes in the human genome. This means that, within the population, few individuals share exactly the same sequences for all of their MHC proteins. What deleterious outcome might occur if all humans shared exactly the same sequence for their MHC proteins?
If all humans shared invariant MHC proteins, there would be a limited diversity of peptides to bind to them. Clever pathogens could evade recognition by T cells by making proteins that peptides couldn't bind to the invariant MHC molecules. It's likely the polymorphism of these proteins in the population ensures a subset of individuals are always able to respond to an infecting pathogen.
Which maternal antibodies may be found in breast-fed newborn babies that are protective against diseases such as diphtheria, tetanus, streptococcal infections, and measles?
IgA & IgG
In addition to IgM, which isotypes of antibodies could be produced in a person with dysfunctional aid
IgG
What is IgM?
IgM is the class of antibody most efficient at binding C1q, making natural antibodies an effective means of activating complement on microbial surfaces immediately after infection and leading to the clearance of bacteria before they become dangerous
Evidence for immune surveillance of tumors comes from a substantially increased incidence of certain cancers in patients with:
Immunodeficiency
somatic recombination;junctional diversity;affinity maturation;isotope switching
In B cells, a very large repertoire of receptors is generated by different mechanisms: - Primary gene rearrangements: - [cc]: random V, D, and J segments are brought together - [dd]: additional diversity added by TdT - Secondary gene rearrangements: - [ee]: increases recognition of the BCR for its antigen - [ff]: affects the effector function of the BCR, without modifying its ability to recognize the antigen.
Individuals with natural killer (NK) cell deficiencies have susceptibilities to infections with herpesviruses and other DNA viruses, as well as with intracellular bacteria such as the mycobacteria that cause tuberculosis. Mycobacterium tuberculosis is a pathogen that infects macrophages and replicates in their phagocytic vesicles. Which effector function of NK cells is likely most important in promoting immunity to M. tuberculosis?
In addition to cytolytic activity, NK cells secrete large amounts of IFN-γ when they are activated. Secretion of IFN-γ is likely the most important effector mechanism by which NK cells help protect against intracellular bacterial infections such as M. tuberculosis. IFN-γ directly activates macrophages to enhance their ability to kill pathogens, including intracellular pathogens replicating in the macrophage. IFN-γ also influences the adaptive immune response by promoting the differentiation of pro-inflammatory TH1 CD4 T cells, which are critical in controlling intracellular bacterial infections. NK cells also produce cytokines and chemokines, such as TNF-α, GM-CSF, CCL3, CCL4, and CCL5 that function to recruit and activate macrophages.
intracellular;mhci;extracellular;mhcii
In general, [w] antigens are presented/associated with [x] to CD8 T cells and [y] antigens are presented/associated with [z] to CD4 T cells.
Neutrophils isolated from certain immunodeficient patients could slowly roll along the endothelial vessel wall but were unable to arrest and migrate across the endothelium barrier. The most likely protein deficient in these neutrophils is:
In integrin called LFA-1
In the absence of infection, what does the COMPLEMENT SYSTEM DO?
In the absence of infection, these proteins circulate in an inactive form. In the presence of pathogens or antibodies bound to pathogens, the complement system becomes 'activated.'
How is the ALTERNATIVE PATHWAY of the COMPLEMENT SYSTEM initiated?
In the alternative pathway (top right), soluble C3 undergoes spontaneous hydrolysis in the fluid phase, generating C3(H2O), which is augmented by the action of factors B, D, and P (properdin).
How is the COMPLEMENT SYSTEM activated?
In the complement system, activation by breaking down proteins into amino acids by enzymes is essential, with many of the complement proteins being broken down by enzymes that successively cleave and activate one another.
Where would you MOST likely find a TLR that recognizes RNA?
In the endosome/lysosome
Where would you most likely find a TLR that recognizes viral RNA
In the endosome/lysosome membrane
How are α-defensins (cryptdins) and the antimicrobial lectin RegIII produced in the intestines(gut)?
In the intestine, Paneth cells (specialized cells deep in the epithelial crypts) produce several kinds of antimicrobial proteins: α-defensins (cryptdins) and the antimicrobial lectin RegIII.
Affinity maturation and class switch of B cells require interaction between germinal center B cells and TFH cells. This interaction occurs:
In the light zone of the germinal center
The Bcl-2 protein was first identified based on its over-expression in a subset of B cell lymphomas, where it was shown to promote the resistance of the tumor cells to apoptosis. Sub-cellular localization experiments would show that Bcl-2 is present:
In the mitochondria where it blocks cytochrome c release. NOTE: Yes. Anti-apoptotic Bcl-2 family proteins function by binding to the mitochondrial membrane to block the release of cytochrome c.
Which description of autoimmune diseases is NOT true?
In type I diabetes patients, pancreatic cells are coated by IgG and consequently removed by phagocytosis.
When Langerhans' cells (dendritic cells of the skin and mucosa) differentiate into fully mature dendritic cells (DCs) they:
Increase expression of B7.1
When Langerhans' cells (dendritic cells of the skin and mucosa) migrate to local lymph nodes and differentiate into fully mature dendritic cells (DCs) they:
Increase expression of B7.1
When macrophages in a tissue encounter bacteria, they release cytokines that induce an inflammatory response. These cytokines act on other immune cells, to recruit them to the site of infection and to enhance their activities. In addition, these cytokines act on the endothelial cells of the blood vessel wall to:
Increase their permeability, allowing fluid and proteins to leak into the tissue
When tissue-resident macrophages encounter bacteria, they release cytokines that induce an inflammatory response. These cytokines act on other immune cells, to recruit them to the site of infection and to enhance their activities. In addition, these cytokines act on the endothelial cells of the blood vessel wall to:
Increase their permeability, allowing fluid and proteins to leak into the tissue
When tissue-resident macrophages encounter bacteria, they release cytokines that induce an inflammatory response. These cytokines act on other immune cells, to recruit them to the site of infection and to enhance their activities. In addition, these cytokines act on the endothelial cells of the blood vessel wall to: A. Secret anti-microbial peptides B. Proliferate, allowing the blood vessel to enlarge C. Increase their permeability, allowing fluid and proteins to leak into the tissue D. Solidify the tight junctions to prevent the bacteria from entering the blood E. Up-regulate microbicidal mechanisms, so they can kill bacteria
Increase their permeability, allowing fluid and proteins to leak into the tissue.
Which of the following is an example of an immune escape mechanism used by some tumor cells?
Increased expression of PD-L1
Yersinia pestis, the causative agent of the bubonic plague, has multiple mechanisms of immune evasion. This Gram-negative bacterium is transmitted from fleas (body temperature, 26°C) to humans (body temperature, 37°C) by flea bites. Studies have shown that the lipopolysaccharide (LPS) produced by Y. pestis grown at 37°C is about 10-fold less potent at stimulating TLR4 signaling than is the Y. pestis LPS from bacteria grown at 26°C. When these two forms of Y. pestis LPS are compared for their abilities to induce responses from human macrophages, one would expect that the 26°C Y. pestis LPS would result in:
Increased production of TNF-alpha and IL-6
Yersinia pestis, the causative agent of the bubonic plague, has multiple mechanisms of immune evasion. This gram-negative bacterium is transmitted from fleas (body temperature, 26C) to humans (body temperature, 37C) by flea bites. Studies have shown that the lipopolysaccharide (LPS) produced by Y. pestis grown at 37C is about 10-fold less potent at stimulating TLR4 signaling than is the Y. pestis LPS from bacteria grown at 26C. When these two forms of Y. pestis LPS are compared for their abilities to induce responses from human macrophages, one would expect that the 26C Y. pestis LPS would result in:
Increased production of TNFa and IL-6
Why are diseases that are the result of homeostatic dysregulation more common now than 100 years ago?
Increasing mismatch between genotype and environment
The hygiene hypothesis has been proposed as an explanation for the rapid increase in allergies and asthma incidence in Western countries over the last half of the century. One line of evidence supporting this hypothesis is:
Individuals of African descent have much higher incidence of atopic disease when living in Western countries
The 'hygiene hypothesis' has been proposed as an explanation for the rapid increase in allergies and asthma incidence in Western countries over the last half century. One line of evidence supporting this hypothesis is:
Individuals of African descent have much higher incidence of atopic disease when living in Western countries.
Several types of pathogens encode proteins that function as superantigens, which activate massive numbers of T cells in an individual. One example is the staphylococcal enterotoxins that cause food poisoning. These superantigens are the exception to the general rule that T cells only recognize specific peptide:MHC complexes, because they:
Induce activation of any T cell whose T-cell receptor uses a particular Vβ region bound by that superantigen
Chemokines such as CXCL8 have a key role in the rapid recruitment of neutrophils to the site in the tissue containing the focus of an infection. In this response, CXCL8 has two different functions. In addition to inducing integrin activation on the neutrophil, CXCL8 also functions to:
Induce directional migration of the neutrophil in the tissue
A key feature of TLR signaling is the ability to induce inflammatory cytokine gene expression extremely rapidly following TLR stimulation. This is accomplished by signaling pathways using several mechanisms to activate transcription factors that are already present in the cell prior to TLR stimulation, but are kept in an inactive state. These signaling pathways use all of the following mechanisms EXCEPT:
Induced phosphorylation preventing protein degradation
In patients with 'CD40 ligand deficiency', T cell-dependent B cell activation is impaired, leading to poor antibody responses to protein antigens. The signaling pathway missing in these patients' B cells is important for:
Inducing NF-κB activation by the noncanonical pathway
Allergic responses to inhaled antigens occur when an individual is first sensitized to the antigen (I.e. the allergen), inducing an immune response, and then has a subsequent exposure to the same antigen. The sensitization phase is characterized by:
Induction of a CD4 T cell type II immune response
Infants and young children with deficiencies in specific complement components present with recurrent respiratory infections caused by extracellular bacteria. The peak age of susceptibility is between 6 and 12 months after birth. At this time, as shown in Figure Q2.12, maternal antibodies acquired by the child during fetal gestation are nearly gone, but the child is not yet generating robust antibody responses to new infections, as indicated by the low circulating levels of IgG and IgA. As children with this immunodeficiency get older, they outgrow this disease and show no further evidence of these recurrent infections. Based on this information, name one likely gene deficiency (in the complement system) that could cause this primary immunodeficiency, and the specific complement pathway likely to be affected. Explain your answer.
Infants and small children with defects in MBL or MASP show recurrent upper respiratory infections by extracellular bacteria due to a defect in the lectin pathway of complement activation. When maternal antibodies get less and the child isn't yet generating robust antibody responses on their own, complement activation can't proceed by the classical pathway. During this time, protection against upper respiratory bacterial infections is highly dependent on the lectin pathway initiated by MBL or collectin binding to the pathogen. Information provided rules out the alternative pathway, since it is initiated by spontaneous C3 cleavage. If there was a defect in C3, or a downstream component of the complement cascade shared by all three pathways, the recurrent infections would not disappear as children age.
Cyclosporin A and tacrolimus (FK506)
Inhibition of calcineurin activity, NFAT activation, and IL-2 production
Sirolimus (Rapamycin)
Inhibition of cell growth and proliferation by inhibiting mTOR activity
(BONUS) Many different viruses encode proteins that function to down-regulate MHC class I expression on host cells following infection with the virus. This immune evasion mechanism allows the virus to hide from CD8 T lymphocytes that normally detect virus-infected cells by using their T cell antigen receptor to recognize viral peptides bound to MHC class I proteins on the surface of the infected cell. To counteract this immune evasion strategy, NK cells have:
Inhibitory receptors that recognize MHC class I proteins
Many different viruses encode proteins that function to down-regulate MHC class I expression on host cells following infection with the virus. This immune evasion mechanism allows the virus to hide from CD8 T lymphocytes that normally detect virus-infected cells by using their T cell antigen receptor to recognize viral peptides bound to MHC class I proteins on the surface of the infected cell. To counteract this immune evasion strategy, NK cells have:
Inhibitory receptors that recognize MHC class I proteins
Many different viruses encode proteins that function to down-regulate MHC class I expression on host cells following infection with the virus. This immune evasion mechanism allows the virus to hide from CD8 T lymphocytes that normally detect virus-infected cells by using their T cell antigen receptor to recognize viral peptides bound to MHC class I proteins on the surface of the infected cell. To counteract this immune evasion strategy, NK cells have:
Inhibitory signals that recognize MHC class I proteins
Which is true regarding LFA-1-ICAM1 interaction between CTL and a target cell
Initial interaction between low-affinity LFA-1 expressed by the CTL and ICAM1 expressed by the target cell is replaced by a high-affinity LFA-1 interaction with ICAM2, if the TCR of the CTL recognizes its target peptide presented on MHC1 of a target cell
MASP
Initiating the protease of lectin
Which of the following is a common consequence of TCR and CCR7 signaling?
Integrin activation
In the GTP-bound state, small GTPases contribute to signaling by:
Interacting with target proteins and altering their activity
Rolling
Interaction of P/E-selectin with sulfated sialyl-Lewis x
Unlike B lymphocytes, T lymphocytes do not generate a secreted form of their antigen receptor after they are activated and proliferate. This is because the effector functions of T cells are restricted to:
Interactions with other cells, such as virus-infected cells or other immune cells
Cytotoxic drugs such as azathioprine and cyclophosphamide
Interference with DNA synthesis
proteasome
Intracellular antigens are degraded in the cytosol by a multiple subunit complex called the [bb].
The mechanism of cross-presentation by dendritic cells is an essential pathway for generating CD8 T cell responses to some intracellular pathogens. If this pathway did not exist, we would be highly susceptible to:
Intracellular pathogens that do not infect and replicate in dendritic cells
The mechanism of cross-presentation by dendritic cells is an essential pathway for generating CD8 T cell responses to some intracellular pathogens. If this pathway did not exist, we would be highly susceptible to:
Intracellular pathogens that do not infect and replicate in dendritic cells.
The antigen receptor on a T cell recognizes a degraded fragment of a protein (i.e., a peptide) bound to a specialized cell surface peptide-binding receptor called an MHC molecule. One key aspect of this system is that the peptides displayed on MHC molecules can be derived from intracellular proteins. This mode of antigen recognition is particularly important in allowing the adaptive immune response to detect infections by:
Intracellular pathogens, such as viruses and some protozoa
What is Commensal Bacteria?
Is nonpathogenic bacteria that helps keep pathogens at bay.
Which of the following statements does NOT apply to IgG?
Is the immunoglobulin that is expressed on immature B-cells
Secondary (or peripheral) lymphoid organs are sites for initiation of adaptive immune responses. Given the rarity of lymphocytes specific for any given antigen and the vast amount of body tissue that must be protected, the system of secondary lymphoid tissues is efficient because:
It concentrates antigens in centralized locations for rare lymphocytes to encounter
When stimulated by binding to bacterial products, the fMet-Leu-Phe (fMLF) receptor triggers multiple responses by phagocytes, including migration and induction of antimicrobial activities. Most of these responses are activated by small GTPases of the Rac and Rho families that are indirectly activated by fMLF receptor stimulation. The fMLF receptor can initiate multiple downstream signaling pathways because:
It couples to a heterotrimetric G protein that has alpha and By subunits with independent activities.
The adaptive immune system uses multiple strategies to generate diversity in our ability to mount responses to a wide array of infectious microorganisms. These strategies include the generation of diverse repertoires of B-cell and T-cell antigen receptors, as well as polymorphism of MHC genes. The polymorphism of MHC genes differs from the diversity of lymphocyte antigen receptors in that:
It creates diversity between individuals in the population rather than within a single individual
The adaptive immune system uses multiple strategies to generate diversity in our ability to mount responses to a wide array of infectious microorganisms. These strategies include the generation of diverse repertoires of B-cell and T-cell antigen receptors, as well as polymorphism of MHC genes. The polymorphism of MHC genes differs from the diversity of lymphocyte antigen receptors in that:
It creates diversity between individuals in the population rather than within a single individual.
briefly describe the COMPLEMENT SYSTEM?
It directly kills some microorganisms and interacts with others to promote their removal by phagocytic cells
What is the alternative pathway C3 convertase is composed of?
It is composed of C3b itself bound to Bb, which is a cleavage fragment of the plasma protein factor B. This C3 convertase, designated C3bBb, has a special place in complement activation because, by producing C3b, it can generate more of itself.
What is the Mucosal Ephithelia
It is the internal epithelia that secretes mucus. Mucus contains many glcoprotiens called Mucins
Once expressed on the surface of host cells, an MHC protein remains stably associated with its bound peptide for several days. This highly stable peptide binding behavior is important because
It prevents peptide exchanges on the cell surface, ensuring that peptide:MHC complexes are reliable indicators of the proteins present inside that host cell.
Once expressed on the surface of host cells, an MHC protein remains stably associated with its bound peptide for several days. This highly stable peptide binding behavior is important because:
It prevents peptide exchanges on the cell surface, ensuring that peptide:MHC complexes are reliable indicators of the proteins present inside that host cell.
What pathogen sensor does the CLASSICAL PATHWAY use ?
It uses a pathogen sensor known as the C1 complex, or C1.
What is a key feature of the ALTERNATIVE PATHWAY?
Its key feature is its ability to be spontaneously activated. It has a unique C3 convertase, the alternative pathway C3 convertase, that differs from the C4b2a convertase of the lectin or classical pathways
Natural killer (NK) cells do NOT:
Kill only by damaging the target cell outer membrane
ICAM-1 binds
LFA-1
Match the following molecules on antigen-presenting cells to their binding partners on T cells: ICAM-1
LFA-1
Integrin-dependent T cell adhesion to antigen-presenting cells increases substantially following TCR stimulation. This increased integrin-dependent adhesion is mediated in part by:
LFA-1 conversion to a high affinity binding state
Which of the following is a common consequence of TCR and CCR7 signaling?
LFA-1 transition to a high-affinity form
Mycobacterium leprae, the causative agent of leprosy in humans, is an intracellular pathogen that resides in the phagosome of macrophages. Leprosy presents in two main clinical manifestations. Tuberculoid leprosy results in the formation of granulomas and a cell-mediated immune response while lepromatous leprosy results in the production of high levels of IgG (hypergammaglobulinemia). If TH2 is produced in high levels during an leprae infection, which type of leprosy would result?
Lepromatous leprosy
Defects in LFA-1 gene lead to
Leukocyte adhesion deficiency (LAD)
T cells are frequently at fault for causing damage in autoimmune disorders and in transplant rejection. As an immunologist, your dream is to discover a method for decreasing T-cell response to self-antigens. Which of the following would be the BEST target for your research
Ligands that block the binding of one co-stimulatory molecule
T cells are frequently at fault for causing damage in autoimmune disorders and in transplant rejection. As an immunologist, your dream is to discover a method for decreasing T-cell response to self-antigens. Which of the following would be the BEST target for your research?
Ligands that block the binding of one co-stimulatory molecule
Match the step in neutrophil recruitment into inflamed tissues with the key effectors involved: endothelial cell activation rolling neutrophil activation strong adhesion/arrest diapedesis
Local secretion of pro-inflammatory cytokines Interaction of endothelial selectins with ligands on leukocytes Chemokine signaling Integrins on leukocytes bind endothelial ICAMs Endothelial and neutrophil CD31 (PECAM)
Explain why low exposure to environmental microorganisms/commensals is harmful to physiology in the context of the immunity
Low exposure to environmental microorganisms are thought not to develop efficient immunoregulatory mechanisms and to be most susceptible to the development of allergic disease.; The commensal microbes are antagonists of pathogenic microorganisms and protect intestinal tissue from infection and injury; Commensals are needed for immunomodulatory purposes
Which disease is NOT an organ-specific autoimmune disease?
Lupus
The effector activities important in eliminating infectious organisms from our bodies can be categorized into four different groups: cytotoxicity, intracellular immunity, mucosal and barrier immunity, and extracellular immunity. Briefly describe why the immune system requires four different effector modules for maximum protection.
Lymphoblasts up-regulate many biosynthetic and metabolic pathways to produce macromolecules and energy used for rapid cell division. Many of these processes require new mRNA and protein synthesis by the activated lymphocyte. For the purpose of energy production, lymphoblasts up-regulate glucose transporters and enzymes that are used in the glycolytic pathway.
Which of the following is NOT one of the four broad categories of disease-causing microorganisms, or pathogens?
Lymphocytes
What is Lysozyme?
Lysosyme is an antimicrobial enzyme that digests the cell wall of bacteria.
How do LYSOZYMES digest the cell wall of bacteria.
Lysozyme cleaves β-(1,4) linkages between GlcNAc and MurNAc, creating a defect in the peptidoglycan layer and exposing the underlying cell membrane to other antimicrobial agents. Lysozyme is more effective against Gram-positive bacteria because of the relatively greater accessibility of the peptidoglycan
How does Lysozyme breakdown bacterial cell walls?
Lysozyme selectively cleaves the glycan linkage between N-acetylglucosamine and N-Acetylmuramic acid (two sugars) and is more effective in acting against Gram-positive bacteria, in which the peptidoglycan cell wall is exposed, than against Gram-negative bacteria, which have an outer layer of LPS covering the peptidoglycan layer.
What exactly do lysozymes do?
Lysozyme selectively cleaves the β-(1,4) linkage between these two sugars and is more effective in acting against Gram-positive bacteria, in which the peptidoglycan cell wall is exposed, than against Gram-negative bacteria, which have an outer layer of LPS covering the peptidoglycan layer
Which of the following statements is TRUE of lysozyme?
Lysozyme splits peptidoglycan
What are Lysozymes and what do they do?
Lysozymes are a glycosidase that breaks a specific chemical bond in the peptidoglycan component of the bacterial cell wall.
Which of the following statements is TRUE of lysozyme?
Lysozymes split peptidoglycans
The cell type in the epithelium of the intestine that functions to deliver antigen from the intestinal lumen to lymphoid cells in the gut wall is
M cell
C6, C7, C8, C9
MAC complex
CD1d and MR1 both present non-peptide antigen to types of invariant T cells. In the case of MR1, these cells are called
MAIT cells
Associate with MBL and cleave C4
MASP2
Match the T cell integrin proteins to their binding partners on endothelial cells: α4:β7 integrin
MAdCAM-1
_____ is the vascular addressin found on endothelial cells of intestinal mucosa that binds to integrins of gut-homing effector lymphocytes.
MAdCAM-1
___________ is the vascular addressin found selectively on the endothelium of blood vessels in intestinal mucosal tissues. It binds to integrins of gut-homing effector lymphocytes.
MAdCAM-1
Which of the following is not an opsonin
MBL
How does MANNOSE-BINDING LECTIN (MBL) bind to microbial surfaces?
MBL has a low affinity for mannose, fucose, and N-acetylglucosamine (GlcNAc) which are found on the surfaces of some pathogens. So in order MBL to bind to them, these carbs have to be repetitive in order for them to bind. Thus MBL has high total binding strength
What happens to MANNOSE-BINDING LECTIN (MBL) in plasma?
MBL in plasma forms complexes with the MBL-associated serine proteases MASP-1, MASP-2, and MASP-3.
You cross a BALB/c mouse with a CBA mouse.. What classes of MHC molecules will the F1 progeny express on its liver cells ___________ and its macrophages _____________
MHC 1 MHC 1 and 2
CD8+ T-cells recognize their antigen presented by which molecules?
MHC Class I
CD4positive T cells recognize their antigen presented by which molecule?
MHC Class II
CD4positive T cells recognize their antigen presented by which molecules?
MHC Class II
invariant chain/CLIP
MHC II molecules are prevented from loading peptide within the ER by the [aa].
CD4+ cells recognize their antigen presented by which molecules?
MHC class II
Peptide editing is an important component of antigen presentation for both MHC class I and MHC class II pathways, as it drives the preferential presentation of high-affinity binding peptides. For MHC class II peptide editing, HLA-DM plays a key role. In the absence of HLA-DM:
MHC class II molecules traffic to the cell surface with CLIP in their binding sites.
Stressed or infected cells express MHC molecules to activate the NKG2D receptor on NK cells, γ:δ T cells, or some CD8 T cells. Which of the molecules below are the ligands of NKG2D?
MHC class Ib genes such as MIC-A, MIC-B, and RAET1
MHCa mice that are irradiated and reconstituted with MHCa x b bone marrow would accept grafts from which of the following donors?
MHCa, MHCb, and MHCa x b
NKG2D is an activating receptor expressed on NK cells, gamma delta T cells, and some cytotoxic alpha beta T cells. When stressed or infected cells upregulate proteins that bind to and activate NKG2D molecules, the stressed or infected cells will be killed. This pathway elies on the fact that stressed or infected cells upregulate
MICA and MICB expression
Which of the following is not an antibody effector function?
Macrophage activation
Under which of the following conditions would T-cell activation be LEAST likely to occur?
Macrophages are fixed with paraformaldehyde, then incubated with antigen, then incubated with antigen-specific T cells.
Where is MANNOSE-BINDING LECTIN (MBL) made and where does it reside?
Made in the liver and circulates in the blood in low concentrations. But in the presence of an infection,it's production is increase during acute phase response.
The injection of tuberculin into the skin of a sensitized individual elicits:
Mantoux reaction
Local TH1 response to injected tuberculin in previously infected individuals
Mantoux test
Which of the following functions is not elicited by antibody binding to Fcγ receptor?
Mast cell degranulation
Anaphylaxis can be triggered by cross-linking of IgE receptors on:
Mast cells
b. Local secretion of TNF-alpha and other cytokines
Match the step in neutrophil recruitment into inflamed tissues with the key effectors involved: Endothelial cell activation
e. Interaction of P/E-selectin with sulfated sialyl-Lewis x
Match the step in neutrophil recruitment into inflamed tissues with the key effectors involved: Rolling
d. Neutrophil squeezes between endothelial cells
Match the step in neutrophil recruitment into inflamed tissues with the key effectors involved: diapedesis
a. Neutrophil LFA-1 interacts with endothelial ICAM-1
Match the step in neutrophil recruitment into inflamed tissues with the key effectors involved: strong adhesion
c. CXCL8 signaling through CXCR2 induce LFA-1 change in conformation
Match the step in neutrophil recruitment into inflamed tissues with the key effectors involved: neutrophil integrin assuming active state
Which of the statements below is TRUE about somatic hypermutation?
May decrease affinity of an antibody
Which of the statements below is TRUE about somatic hypermutation?
May decrease the affinity of an antibody
What are the three barriers that must be crossed for infection to be established?
Mechanical, chemical, and microbial
It is well documented that antibody affinities for an immunizing antigen continue to increase upon successive rounds of immunization. This is due to the fact that:
Memory B cells can re-enter germinal centers and undergo additional somatic hypermutation
Memory T cells, effector T cells, and naïve T cells share several characteristics. Which of the following descriptions could only be said of memory T cells?
Memory T cells are activated by any APC
The secondary response to an antigen is often significantly stronger because:
Memory cells rapidly differentiate to parasite specific T and B cells upon antigen recognition
What is the cell type MOST characteristically associated with the gut-associated lymphoid tissue (GALT)?
Microfold (M) cell
Match the following cell types with their specialized functions: Uptake of pathogens for presentation by dendritic cells
Microfold (M) cells
Uptake of pathogens for presentation by dendritic cells
Microfold (m) cells
What is the cell type MOST characteristically associated with the gut-associated lymphoid tissue (GALT)?
Microfold (m) cells
What are PATHOGEN-ASSOCIATED MOLECULAR PATTERNS (PAMPs)?
Molecules specifically associated with groups of pathogens that are recognized by cells of the innate immune system
Celiac disease occurs when an individual makes an aberrant immune response to a protein in gluten, such as α-gliadin. Evidence suggests that very few proteins are able to elicit the immune response that causes celiac disease. A key piece of this evidence is that:
More than 95% of patients express the MHC class II DQ2 allele.
