Immunology Questions

2.16 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

2.16 chapter 2 questions

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

Early studies analyzing the aterm-59ntibody 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

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 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 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.

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: A. Amplify the local innate immune response by entering tissues that are infected B. Phagocytose and kill pathogens in the blood C. Line the endothelial surfaces of the blood vessels with phagocytic cells D. Enter lymph nodes and patrol for infecting microbes in these organs

Amplify the local innate response by entering tissues that are infected

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

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

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.

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

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.

Create a blocking method to the sensor cells. 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.

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

2.20 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.

DAF/CD55 is a complement inhibitory protein that inactivates any C3 convertase that may form on host cell surfaces.

2.15 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

An infection in the skin, such as a pimple, often produces pus. The major component of pus is

Dead and dying neutrophils

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

2.23 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

Engagement of complement receptors on phagocytes by C3b and its cleavage

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

2.3 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. 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

True/False All mammalian TLRs have been shown to directly bind to microbial products, leading to TLR signaling.

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

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.

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

3.13 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

Induced phosphorylation preventing protein degradation

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

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.

It couples to a heterotrimetric G protein that has alpha and By subunits with independent activities.

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.

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

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

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

Prevent fusion of phagosomes with lysosomes

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

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

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 immunoterm-60globulin domains are

Similar but not identical in amino acid sequence when comparing the domains in a single heavy chain polypeptide

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

2.7 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? 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. PICTURE ON LAPTOP

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

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

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

2.17 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.

The C3 convertase of the alternative pathway contains C3b, and can generate more of itself

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.

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

2.5 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.

The antibiotics kill many of the commensal organisms in the reproductive tract, allowing overgrowth of the fungus

3.14 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 neutrophilsE. The inflammatory complement fragments, C3a and C5a

The antiviral cytokine, type I interferon

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 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 detective immune response occurs too rapidly following infection to be due to a defect in B or T lymphocytes responses

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?

They only activate when they encounter a recognized antigen. 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.

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.

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 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

The essential immune mechanism required for resistance to each category of pathogen

2.29 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

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 problem 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

The extensive polymorphism of MHC genes in the human population

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.

1.19 True/False: 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

2.18 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

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

The presence of adenosine residues in viral RNA The presence of adenosine residues would not discriminate between viral and host RNA, as both types contain these residues.

2.11 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.

The rapid hydrolysis of active C3b in solution, rendering it inactive.

2.30 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

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

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: 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: 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

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 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

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.

1.36 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.

2.27 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.

Uncontrolled complement activation leads to the depletion of serum complement proteins.

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

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.

2.1 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 E. Viruses

Virus-infected 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

chemokines that induce directed migration of blood monocytes

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: A. Red blood cells B. Macrophages C. Lymphocytes D. Endothelial cells E. Granulocytes

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

Like innate sensors of infections (TLRs, NLRs, RLRs), antibodies frequently recognize nucleic acids of pathogenic organisms.

false

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

from the blood by crossing the high endothelial venules

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

interactions with other cells, such as virus-infected cells or other immune 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: 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

intracellular pathogens, such as viruses and some protozoa

2.8 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.

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: 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.

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: A. Production of antibodies B. Infiltration by white blood cells C. Mucus production D. Increased saliva production E. Fever

mucus production 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.

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

providing a mechanism for phagocytes bearing complement receptors to recognize and ingest the bacteria

2.4 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

secretion of antimicrobial peptides by epithelial cells

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.

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

some antigen receptors might recognize the individuals on cells or antigens

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

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: 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

the important role of T follicular helper cells in generating protective antibody responses

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

the increased rapidity and magnitude of the secondary response to the same antigen

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

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

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 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 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.

they neutralize the virus or toxin, preventing it from attaching to and entering our cells

2.13 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.

they only bind to carbohydrate side chains and oligosaccharide modifications found on pathogen surfaces but on host cell membranes

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

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

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: 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

up-regulate synthesis of mRNA and proteins, some of which encode for glucose transporters and enzymes used for glycolysis

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

vaccines 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.

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.

viruses like HIV and influenza undergo antigenic variation to evade previous immune responses