Immunology Final Exam

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.

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)

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)

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: 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

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

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

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

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

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.

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

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

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

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

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 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.

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

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

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.

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.

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.

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.

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.

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.

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

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

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

Our immune system efficiently kills all categories of microbes that attempt to colonize our bodies 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 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 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.

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

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.

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

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

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

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

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.

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

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

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)

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

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

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

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

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

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 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.

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

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.

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.

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.

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.

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.

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

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 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

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

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.

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

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.

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.

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.

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.

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.

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

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.

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

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.