Immuno Chapter 11, Immuno Chapter 10, immuno 8), Immuno Chapter 12

11.12 Multiple choice: Helicobacter pylori is a human gastrointestinal (GI) pathogen that can lead to a state of chronic GI inflammation in some individuals, and has been linked to gastric ulcers and other diseases. Studies have shown that human mucosal gastric biopsies of infected individuals have dendritic cells producing IL-23, and that human monocytes isolated and cultured from healthy individuals produce IL-23, but not IL-12, in response to stimulation with live H. pylori. Given these findings, which of the following responses would be enhanced in the GI tract of H. pylori-infected individuals compared to uninfected individuals? A. Mucus production by goblet cells B. Recruitment of neutrophils C. Recruitment of eosinophils D. Production of nitric oxide and superoxide E. Production of IL-13

B. Recruitment of neutrophils

11.2 Multiple choice: IL-23 is a cytokine made by macrophages and dendritic cells in response to extracellular bacterial and fungal infections. Mice with a genetic defect in the production of IL-23 are highly susceptible to the gastrointestinal bacterial pathogen, Citrobacter rodentium. Thus, unlike wild-type mice which clear the infection, mice that fail to produce IL-23 succumb to the bacteria and die 1-2 weeks post-infection. Yet, this cytokine does not directly act on the bacteria nor does it function to recruit the granulocytes that are needed to eliminate the pathogen. Instead, IL-23: A. Functions as a chemoattractant for eosinophils and basophils B. Stimulates IL-17 and IL-22 production by ILC3 cells C. Activates tissue-resident ILC2 cells to produce IL-5 and IL-13 D. Induces the differentiation of naive CD8 T cells into cytotoxic T cells E. Stimulates gastrointestinal epithelial cells to produce antimicrobial peptides

B. Stimulates IL-17 and IL-22 production by ILC3 cells

11.6 Multiple choice: Individuals with the HIV-induced immunodeficiency disease AIDS have a progressive loss in the number of CD4 T cells in their bodies. These patients have a greatly increased rate of life-threatening disease caused by the inability of their immune system to control infections of the intracellular bacterium, Mycobacterium tuberculosis (Mtb). Mtb infects macrophages and then replicates in the cell's phagosomes. The most important immune mechanism lacking in these patients that leads to their increased susceptibility to Mtb is a defect in: A. CD4 T cell help for cytotoxic effector CD8 T cells B. The activation of macrophages by TH1 effector cells C. The production of opsonizing antibodies that requires TFH cell help for B cells D. The production of TNF- by the infected macrophages E. The recruitment of neutrophils to the site of infection

B. The activation of macrophages by TH1 effector cells

11.19 Multiple choice: Immunological memory in humans has been examined by assessing responses in individuals who were given the vaccinia virus to induce immunity against smallpox. Antiviral CD4 and CD8 T cell responses could be detected many years after the vaccinia immunization, but declined with an estimated half-time of about 10 years. In contrast, antiviral antibody responses were maintained at a relatively constant level, with a barely detectable decline over decades. The persistence of antiviral antibodies for years after immunization is likely due to: A. The presence of CD4 T cell help for memory B cells B. The presence of long-lived antibody secreting plasma cells C. The periodic reactivation of memory B cells by low levels of antigen exposure D. The persistence of the virus in the immunized host E. The presence of pro-survival cytokines, such as IL-7 and IL-15

B. The presence of long-lived antibody secreting plasma cells

8.12 Multiple choice: B-1 B cells are considered a component of the innate rather than the adaptive immune response. The antibodies produced by B-1 B cells generally recognize capsular polysaccharide antigens found on many bacteria and viruses. These antibodies are considered part of the innate immune response because: A. They recognize pathogens rather than innocuous harmless antigens. B. They are produced prior to the exposure to the pathogen. C. They are specific for carbohydrate rather than protein antigens. D. They are secreted by B-1 B cells starting at 48 hour post-infection. E. They are not generated by the process of VD-J recombination of immunoglobulingenes.

B. They are produced prior to the exposure to the pathogen.

11.9 Multiple choice: Leprosy is a disease caused by the intracellular bacterium Mycobacterium leprae, which infects macrophages and replicates in their phagosomes. Human patients with leprosy have a persistent infection of the mycobacteria, as their immune systems are unable to complete eradicate the pathogen. Furthermore, two different forms of the disease have been identified. Some patients have many skin lesions containing a large number of bacteria with little inflammatory response. This is the very disfiguring form of the disease, and is known as lepromatous leprosy. In other patients, few skin lesions and only occasional bacteria are observed, and the skin lesions are accompanied by a robust inflammatory response. These patients have the form of the disease known as tuberculoid leprosy. If one examined a skin biopsy from a patient with tuberculoid leprosy, one would expect to see: A. A large influx of neutrophils and other granulocytes B. A widespread occurrence of tissue necrosis C. A substantial number of granulomas D. Evidence of large numbers of dead or dying mycobacteria E. A large number of skin epithelial cells with intracellular bacteria

C. A substantial number of granulomas

12.1 Multiple choice: The mucosal immune system provides protection for a vast area of the body and contains three-quarters of all the lymphocytes in the body. A key feature of the mucosal immune system is its: A. Ability to respond to thousands of different bacterial species B. Inability to provide adequate protection, leading to millions of deaths per year due to mucosal infections C. Ability to avoid responding to the large numbers and differing species of commensal microbes D. Use of the identical mechanisms and response features compared to the systemic immune system E. Inability to produce antibodies that cross epithelial barriers

C. Ability to avoid responding to the large numbers and differing species of commensal microbes

11.20 Multiple choice: A set of mice are each immunized with one of the following as shown in Figure Q11.20. Mouse A is immunized with tetanus toxoid protein. Mouse B is immunized with the Haemophilus influenzae type b polysaccharide antigen. Mouse C is immunized with a conjugate of the diphtheria toxoid protein linked to H. influenzae type b polysaccharide. Mouse D is left unimmunized (naive). Four weeks later the spleen cells from each mouse are isolated, and B lymphocytes and T lymphocytes from each spleen cell population are purified. When mixed together in culture together with a conjugate antigen of the tetanus toxoid protein linked to the to H. influenzae type b polysaccharide, which combination of spleen cells would generate a memory B cell response? A. B lymphocytes from mouse B plus T lymphocytes from mouse B B. B lymphocytes from mouse A plus T lymphocytes from mouse A C. B lymphocytes from mouse C plus T lymphocytes from mouse A D. B lymphocytes from mouse C plus T lymphocytes from mouse D E. B lymphocytes from mouse B plus T lymphocytes from mouse D

C. B lymphocytes from mouse C plus T lymphocytes from mouse A

8.30 Multiple choice: While many cell types in the thymus are able to induce negative selection of developing self-reactive thymocytes, bone marrow-derived antigen-presenting cells, such as macrophages and dendritic cells, appear to be the most important for this process. One likely reason for the prominent role of bone marrow derived antigen-presenting cells in inducing negative selection of developing thymocytes is: A. Bone marrow-derived antigen-presenting cells are the most abundant stromal cells in the thymus. B. Bone marrow-derived antigen-presenting cells are very good at inducing mature T cell activation. C. Bone marrow-derived antigen-presenting cells are highly phagocytic and have specialized mechanisms for presenting peptides on both MHC class I and class II. D. Bone marrow-derived antigen-presenting cells are concentrated in the thymic medulla where negative selection is most prominent. E. Bone marrow-derived antigen-presenting cells are hematopoietic in origin, so share the same genetic make-up as the developing thymocytes.

C. Bone marrow-derived antigen-presenting cells are highly phagocytic and have specialized mechanisms for presenting peptides on both MHC class I and class II.

8.15 Multiple choice: The thymic cortex has a substantial population of macrophages in addition to the developing T cells (i.e., thymocytes). These macrophages are extremely useful in: A. Eliminating bacterial infections in the thymus B. Producing cytokines that promote T cell maturation C. Engulfing apoptotic thymocytesD. Maintaining the structural integrity of the thymic organ E. Inducing inflammatory signals to increase blood flow to the thymus

C. Engulfing apoptotic thymocytes

10.25 Multiple choice: Some individuals with repetitive exposure to high doses of Schistosoma mansoni develop resistance to re-infection by this helminthic parasite. In contrast, other individuals remain highly susceptible. Population studies showed that resistant individuals had increased numbers of circulating eosinophils in their blood compared to susceptible individuals, and further, that these eosinophils had increased levels of: A. Complement receptor, CR1 B. Mannose binding lectin C. Fc(epsilon)RII, the low affinity IgE receptor D. Fc(gamma)RII-B, the inhibitor IgG receptor E. Anti-microbial ficolins

C. Fc(epsilon)RII, the low affinity IgE receptor

8.28 Multiple choice: MHC class II molecules expressed on the surface of thymic cortical epithelial cells normally have a wide repertoire of different peptides bound to them. By engineering a construct that fuses the MHC class II protein to a single peptide sequence, and expressing this construct in thymic cortical epithelial cells that have their endogenous MHC class II genes knocked out, it is possible to generate a mouse line where all MHC class II proteins expressed on all thymic cortical epithelial cells are bound to the same peptide. These mice are often referred to as 'single-peptide' mice. Examination of the T cell developing in these single peptide mice would likely show: A. A significant reduction in the numbers of mature CD4 T cells B. No change in the numbers of mature CD4 T cells C. A block in T cell development at the CD4+CD8+ double-positive stage D. A repertoire of T-cell receptors on mature CD4 T cells restricted to a single V E. A block in T cell development at the CD4-CD8- double-negative stage

A. A significant reduction in the numbers of mature CD4 T cells

12.20 Multiple choice: Patients receiving hematopoietic stem cell transplants often suffer from graft-versus-host disease (GVHD), involving immune-mediated damage to the gastrointestinal (GI) tract. The symptoms of GVHD include nausea, vomiting, diarrhea, and abdominal cramping due to epithelial cell apoptosis and inflammatory leukocyte infiltration into the GI epithelium. One proposed treatment has been tested in mouse models of GVHD for potential therapeutic benefit. This treatment is: A. Administration of IL-22 B. Administration of anti-microbial peptides C. Administration of mucosal (M2) macrophages D. Administration of TGF- E. Administration of IL-1 + IL-6

A. Administration of IL-22

10.2 Multiple choice: The vaccine to Haemophilus influenzae type b is called a conjugatevaccine. It is composed of the tetanus toxoid protein conjugated to the capsular polysaccharide of the H. influenzae type b bacteria. When used to vaccinate infants, the antibody response generated by this vaccine would include: A. Antibodies to the bacterial polysaccharide and the tetanus toxoid B. Antibodies to the tetanus toxoid only C. Antibodies to the bacterial polysaccharide only D. Antibodies that only bind to the protein-polysaccharide conjugate in the vaccine E. Antibodies that recognize the polysaccharide capsule when shed by the bacteria

A. Antibodies to the bacterial polysaccharide and the tetanus toxoid

12.12 Multiple choice: Secretory IgA produced in the epithelium of mucosal surfaces has several functions in protective immunity. Among these are neutralization of pathogens or toxins in the gastrointestinal tract lumen or in epithelial cell endosomes, neutralization of pathogens or toxins that cross the epithelial barrier, and transport of pathogens or toxins across M cells for delivery to lamina propria dendritic cells. All of these functions share the common feature that they: A. Fail to induce local inflammation in the gastrointestinal epithelium B. Are efficient at inducing opsonization of pathogens for uptake by phagocytes C. Are efficient at inducing complement activation D. Fail to completely protect the epithelium from cytotoxic effects of pathogens E. Induce IgA-secreting plasma cells to produce increased amounts of secretory IgA

A. Fail to induce local inflammation in the gastrointestinal epithelium

11.15 Multiple choice: Salmonella typhimurium is a Gram-negative bacterial pathogen that infects its host via the gastrointestinal (GI) tract. Early in infection, the bacteria enter and replicate in gut epithelial cells, where the infection provokes a type 3 response, including the development of TH17 cells, in the GI tract. However, this type 3 response in the GI tract does not eradicate the pathogen, as S. typhimurium has evolved strategies to evade the TH17 response and to spread systemically by infecting and replicating in macrophages. Therefore, a second phase of the immune response is required to completely eliminate the pathogen from the body, as has been demonstrated in mouse models of S. typhimurium infection. These experiments in mouse models likely showed that: A. IFN-gamma is required to clear S. typhimurium from the body. B. IL-17 is required to clear S. typhimurium from the body. C. IL-22 is required to clear S. typhimurium from the body. D. IL-13 is required to clear S. typhimurium from the body. E. IL-4 is required to clear S. typhimurium from the body.

A. IFN-gamma is required to clear S. typhimurium from the body

11.23 Multiple choice: Following an acute virus infection in which the host clears the virus by approximately one week post-infection, a population of virus-specific memory CD8 T cells is maintained and can be detected for months to years post-infection. In mice with a knockout of a single cytokine, virus-specific memory CD8 T cells cannot be maintained, and disappear over time as shown in Figure Q11.23. The most likely identity of the cytokine that is missing in these knockout mice is: A. IL-15 B. IL-2 C. IL-21 D. IL-23 E. IL-4

A. IL-15

11.7 Multiple choice: Infections of intracellular pathogens (e.g., mycobacteria, listeria, toxoplasma, viruses, etc.) cause a rise in the numbers of monocytes in the blood, a symptom known as monocytosis. In the cases of these infections, monocytosis is likely caused by: A. Increased production of monocytes in the bone marrow induced by TH1 cytokines B. Loss of monocytes into tissues due to inflammation, leading to increased production in the bone marrow C. Differentiation of blood monocytes into macrophages, inducing bone marrow production of new monocytes D. Sticking of blood monocytes to vessel walls due to integrin binding, reducing the numbers of monocytes in the circulation E. Apoptosis of monocytes caused by the toxic effects of the infecting pathogen

A. Increased production of monocytes in the bone marrow induced by TH1 cytokines

8.4 Multiple choice: The pre-B-cell receptor provides an important signal that induces transition of pro-B cells to pre-B cells. An important characteristic of this receptor is that: A. It signals without binding to an extracellular ligand. B. It is composed of immunoglobulin heavy chains and the VJ region of a rearranged light chain. C. It is expressed at very high levels on the surface of the pro-B cell. D. It signals without requiring association with B-cell receptor signaling subunits, Ig and Ig. E. It signals without requiring the B-cell receptor signaling kinase, BTK.,

A. It signals without binding to an extracellular ligand.

12.3 Multiple choice: Salmonella typhimurium is the causative agent of typhoid fever, and infects the host by translocating across the intestinal epithelium. Recent studies have shown that S. typhimurium produces an effector protein called SopB that induces intestinal enterocytes to differentiate into M cells. This is beneficial to the bacteria because: A. S. typhimurium gains access to the host by crossing the intestinal epithelium inside M cells. B. M cells are unable to secrete antimicrobial peptides as do the enterocytes. C. M cells are unable to secrete mucus as do the enterocytes. D. S. typhimurium utilizes the M cell metabolic machinery for its proliferation. E. M cells lack the pattern recognition receptors that induce innate responses to pathogens.

A. S. typhimurium gains access to the host by crossing the intestinal epithelium inside M cells.

10.18 Multiple choice: Individuals with a genetic polymorphism in the Fc receptor, FcRIIa (CD32), have an increased susceptibility to bacterial meningitis (inflammation of the membranes (meninges) surrounding the brain and spinal cord) caused by the encapsulated bacterium, Neisseria meningitidis. This polymorphism reduces the efficiency with which the phagocytes expressing FcRIIa bind to the constant region of this receptor's target antibody. The reason this FcRIIa-dependent response it the major form of protection against Neisseria meningitidis is because: A. T cells are unable to enter the brain and spinal cord. B. Mast cells are unable to localize to the meninges. C. IgG antibodies are the major isotype able to diffuse into tissues. D. IgM antibodies do not have high enough affinity to provide protection. E. Neutrophils are unable to phagocytose encapsulated bacteria.

C. IgG antibodies are the major isotype able to diffuse into tissues.

12.24 Multiple choice: When mice are born, their intestinal lamina propria lacks TH17 effector cells. These cells develop after birth due to: A. Stimulation by antigens derived from commensal microbes that populate the gastrointestinal tract after birth B. Stimulation by retinoic acid from dietary sources C. Stimulation by IL-10 produced from FoxP3+ regulatory T cells D. Stimulation by short-chain fatty acids derived from commensal microbes that populate the gastrointestinal tract after birth E. Stimulation by antimicrobial peptides produced by intestinal epithelial cells

A. Stimulation by antigens derived from commensal microbes that populate the gastrointestinal tract after birth

8.19 Multiple choice: Unlike alpha:beta T cells, gamma:derta T cells are considered to be components of the innate immune system. One feature of gamma:derta T cells that leads to their classification as innate cells is: A. That they migrate from the thymus directly to barrier surfaces such as mucosa and epithelia B. Their ability to produce pro-inflammatory cytokines C. That their T-cell receptors are germline encoded rather than a product of VD-J recombination

A. That they migrate from the thymus directly to barrier surfaces such as mucosa and epithelia

10.16 Multiple choice: Two different vaccines have been developed that protect vaccinated individuals against pneumococcal disease, a bacterial infection that causes pneumonia, meningitis and sepsis (blood stream infection). This disease is caused by the bacteria, Streptococcus pneumoniae. One vaccine, PPSV23, is a mixture of polysaccharides isolated from 23 different serotypes of S. pneumoniae. The second vaccine, PCV13, is a conjugate vaccine made from polysaccharides of 13 different serotypes of the bacteria conjugated to diphtheria toxoid (inactivated toxin protein). The PPSV23 vaccine is only given to adults, whereas infants and small children are given PCV13. This is because: A. Adults are likely exposed to more different strains (serotypes) of S. pneumoniae than infants. B. Adult B cells don't require TFH cells to make antibody responses. C. Infant B cells are immature and don't respond to TI-2 antigens. D. Adult B cells respond more robustly than infant B cells to B-cell mitogens. E. Infant B cells are more dependent on the cytokine BAFF.

C. Infant B cells are immature and don't respond to TI-2 antigens.

8. 29 Multiple choice: Proteins found in the circulation travel throughout the body, including the thymus. One example is serum albumin. Developing T cells with T-cell receptors specific for peptides of human serum albumin bound to MHC class II molecules would likely be: A. Positively selected and would mature into CD4 T cells B. Positively selected and would mature into CD8 T cells C. Negatively selected in the thymus and deleted from the mature repertoire D. Targeted for peripheral mechanisms of self-tolerance after emigrating from the thymus E. Excluded from the T cell zones of the spleen after emigrating from the thymus

C. Negatively selected in the thymus and deleted from the mature repertoire

8.23 Multiple choice: Approximately one in every three alpha:beta T cells expresses two different rearranged TCR alpha chain proteins. Yet T cells are still considered to have 'clonal specificity' for recognizing antigen. The reason for asserting that each T cell has a single functional specificity for recognizing antigen is that: A. Only one of the two TCR chains expressed by a T cell will pair with its TCR chain. B. T cells expressing two different TCR chains will die by apoptosis when they are activated. C. Only one T-cell receptor expressed by each T cell will recognize peptide presented by self-MHC molecules. D. The majority of T cells in an individual will never encounter their specific peptideMHC ligand and so will not be part of an immune response. E. The majority of T cells are self-reactive and therefore eliminated during their development in the thymus.

C. Only one T-cell receptor expressed by each T cell will recognize peptide presented by self-MHC molecules.

8.2 Multiple choice: A key step in the development of B cells is the expression of the RAG-1 and RAG-2 recombinase proteins. The up-regulation of RAG-1 and RAG-2 in early pro-B cells is induced by: A. The cytokine IL-7, which is made by bone marrow stromal cells B. The chemokine CXCL12, which is made by bone marrow stromal cells C. The B cell-specific transcription factors E2A and EBF D. Signaling through the Igα subunit of the B-cell receptor complex E. Signaling through the FLT3 receptor tyrosine kinase binding to membrane-boundFLT3,

C. The B cell-specific transcription factors E2A and EBF

12.14 Multiple choice: Mice lacking the poly Ig receptor (pIgR) have an immunodeficiency disease characterized by increased susceptibility to mucosal infections and an increase in the penetration of commensal microbes into the body's tissues. Yet, a genetic deficiency in the production of IgA antibodies is the most common form of human immunodeficiency, and is generally a mild disease and often even asymptomatic. This dichotomy can be explained by: A. The difference in the immune system between mice and humans B. The different types of commensal microbes found in mice and humans C. The ability of pIgR to transport IgM across the gut epithelium D. The reduced exposure of humans compared to mice to pathogens that infect via the gastrointestinal epithelium E. The development of improved human hygiene, including pasteurization

C. The ability of pIgR to transport IgM across the gut epithelium

10.4 Multiple choice: CXCR5 is the receptor for the chemokine CXCL13, secreted by follicular stromal cells and follicular dendritic cells in the B cell zones (i.e., lymphoid follicles) of secondary lymphoid organs. A conditional knockout mouse in which CXCR5 was specifically deleted only in T cells would have: A. No defects in any type of antibody response B. Defects in the initial activation of all B cells C. A lack of discrete B cell and T cell zones in the lymphoid organ D. A defect in T cell-dependent antibody responses E. An increased number and size of germinal centers

D. A defect in T cell-dependent antibody responses

8.6 Multiple choice: In different mammalian species, the ratio of B cells expressing versus light chain-containing antibodies is about 65%:35%. In other species, such as mice, this ratio is vastly different, at 95%:5%. If a routine blood test performed on an individual revealed that their expressing versus -expressing B cells were seen at a ratio of 95%:5%, this would likely indicate that the individual had: A. An increased number of functional V gene segments compared to the average human in the population B. A defect in allelic exclusion of antibody light chain genes C. A defect in isotypic exclusion of antibody light chains D. A lymphoproliferative disorder E. A genetic defect in one of their two light chain alleles,

D. A lymphoproliferative disorder

8.21 Multiple choice: Like the gamma:derta T cells in other specific mucosal surfaces, the gamma:derta T cells that reside in the epithelial surface of the skin: A. Are slow to respond to activation signals, requiring several days of priming and differentiation B. Are able to produce cytokines that simultaneously induce type I, type II, and type III immune responses C. Are primarily responsible for recruiting macrophages and dendritic cells to the tissue D. Are characterized by the homogeneous expression of a single specific Vgamma and Vderta in their T-cell receptors E. Are unlikely to play any role in immunity to infection, but are likely important for tissue repair

D. Are characterized by the homogeneous expression of a single specific Vgamma and Vderta

12.15 Multiple choice: Infection of mice with the bacterial pathogen, Citrobacter rodentium, elicits a protective immune response in the gastrointestinal tract. This protective response is characterized by two sequential waves of IL-22 production, both induced by IL-23. The early wave of IL-22 production (<day 8 post-infection) is likely produced by: A. Lamina propria dendritic cells responding to PAMPs of the bacterial pathogen B. Lamina propria macrophages responding to PAMPs of the bacterial pathogen C. Naive CD4 T cells induced to differentiate into TH17 cells in the mesenteric lymph node D. Lamina propria ILC3 cells stimulated by dendritic cell-produced IL-23 E. IgA immune complexes transporting bacterial antigens and stimulating lamina propria dendritic cells to produce IL-22

D. Lamina propria ILC3 cells stimulated by dendritic cell-produced IL-23

11.21 Multiple choice: It is well documented that antibody affinities for an immunizing antigen continue to increase upon successive rounds of immunization (i.e., secondary, tertiary, etc.). This is due to the fact that: A. At each round of immunization, new naive B cells are recruited into the response. B. At each round of immunization, the expression of AID increases, leading to higher rates of somatic hypermutation. C. Memory B cells express higher levels of AID than naive B cells, leading to higher rates of somatic hypermutation. D. Memory B cells can re-enter germinal centers and undergo additional somatic hypermutation. E. At each round of immunization, germinal centers become larger and have increased numbers of B cells in them.

D. Memory B cells can re-enter germinal centers and undergo additional somatic hypermutation.

10.19 Multiple choice: Wild-type mice infected with one strain of Influenza A virus (PR8) by intranasal inoculation are protected from intranasal infection by a related Influenza A virus (Beijing), a phenomenon known as cross-protection. These infections are generally localized to the upper respiratory tract. Mice with a homozygous single gene defect in 'gene X' have greatly impaired cross-protection to Influenza A-Beijing following immunization with Influenza A-PR8 by the intranasal route. Gene X likely encodes: A. Fc receptor, FcRIIa B. Complement receptor, CR1 C. TLR adapter protein, MyD88 D. Poly Ig receptor E. AID

D. Poly Ig receptor

11.5 Multiple choice: Initially after an infection, the majority of the T cells present in the tissue at a site of infection are not specific for the infecting pathogen, but over the course of several days, this changes and antigen-specific T cells become enriched at this site. This is because: A. T cells do not use their T-cell receptors during extravasation from blood into tissues. B. Early after infection, there are few antigen-specific T cells in the host. C. Naive T cells do not express the homing receptors to extravasate into sites of inflammation. D. T cells up-regulate CD69 early after activation and are retained in the lymphoid organs. E. T cells require several days to down-regulate CCR7.

D. T cells up-regulate CD69 early after activation and are retained in the lymphoid organs.

12.4 Multiple choice: A healthy intestinal mucosa is one in which induced adaptive immune responses to pathogenic infections are balanced by the lack of responses to innocuous food antigens and commensal microbes. This balance is maintained by an array of different subsets of effector T cells and regulatory T cells that reside in the intestinal epithelium and lamina propria. Although these different T cell subsets have diverse patterns of cytokine production and other effector functions, they share: A. The ability to live for months to years in the intestinal epithelium B. The ability to secrete immunosuppressive cytokines C. The ability to inactivate dendritic cells that have received signals through pattern recognition receptors D. The expression of gut-homing chemokine receptor, CCR9 E. The ability to bind to E-cadherin on the intestinal epithelial cells

D. The expression of gut-homing chemokine receptor, CCR9

11.17 Multiple choice: In the cases of some infections, such as mice infected with adenovirus, the generation of effector cytotoxic CD8 T cell responses needed to clear the infection is dependent on the antigen-presenting dendritic cells receiving stimulation through the CD40 receptor on their surface, a process known as dendritic cell 'licensing'. In this infection system, the dendritic cell would likely receive CD40 receptor stimulation from: A. The activation of a TLR expressed in the dendritic cell B. The up-regulation of CD40 ligand by virus-infected host cells C. The activation of cytosolic nucleic acid sensors in the dendritic cell D. The interaction with a CD4 effector cell expressing CD40 ligand E. The phagocytosis of apoptotic cell debris resulting from the virus infection

D. The interaction with a CD4 effector cell expressing CD40 ligand

8.33 Multiple choice: The final stages of T cell development occur in the thymic medulla, after the developing cells become CD4 or CD8 single-positive. One important change that occurs during this final maturation is: A. The down-regulation of the pre-T-cell receptor alpha (pre-Talpha) chain protein B. The up-regulation of genes encoding effector cytokines and cytolytic effector proteins C. The increased susceptibility to T-cell receptor-induced apoptosis D. The loss of susceptibility to T-cell receptor-induced apoptosis E. The up-regulation of signaling proteins required for T cell activation

D. The loss of susceptibility to T-cell receptor-induced apoptosis

12.6 Multiple choice: Vibrio cholerae causes an acute diarrheal illness that can be fatal if not treated. Several vaccines have been developed in an effort to prevent this disease. The oral cholera vaccine is a mixture of killed Vibrio cholerae bacteria plus additional inactivated cholera toxin protein. Efficacy studies of this vaccine indicate that it prevents 50-60% of the cases of cholera infection observed in non-vaccinated individuals. In contrast, injectable vaccines made from killed bacteria or purified bacterial subunits are substantially less effective at preventing infections. This is likely due to the fact that: A. The injectable vaccine fails to elicit gut-homing immune responses. B. The oral vaccine lasts substantially longer in the body than the injectable vaccine. C. The oral vaccine has a higher concentration of bacterial antigens than the injectable vaccine. D. The oral vaccine contains the inactivated cholera toxin. E. The injectable vaccine does not contain protein epitopes to elicit CD4 helper T cells.

A. The injectable vaccine fails to elicit gut-homing immune responses.

10.12 Multiple choice: Unlike somatic hypermutation, class switching occurs in discrete sequence regions upstream of the immunoglobulin heavy chain coding sequences (called switch regions). One key element in directing the enzyme AID to a specific switch region is the opening of the DNA duplex combined with polymerase stalling during active transcription in that region. A second key feature of directing AID to a specific switch region is: A. The processed RNA from the switch region guides AID to this site in the DNA B. The binding of DNA-PK's to the switch region sequence in the DNA C. The presence of double-stranded breaks in the DNA in this region D. The binding of AID to the RNA polymerase that is transcribing the switch region E. The predominance of G:C base pairs in the switch sequence

A. The processed RNA from the switch region guides AID to this site in the DNA

10.7 Multiple choice: The germinal center is a region within the secondary B cell follicle where sustained B cell proliferation and differentiation take place. The processes of B cell proliferation and differentiation, including affinity maturation and class switching, require periodic interactions of the germinal center B cells with CD4 TFH cells. These periodic interactions between the B cells and TFH cells can occur: A. When B cells cycle between the dark zone and the light zone of the germinal center B. When B cells leave the germinal center and migrate through the T-cell zone on their way to the blood C. When B cells migrate and form a primary focus of antibody-secreting plasmablasts in the medullary cords of the lymph node D. When B cells migrate to the border between the T-cell zone and the B-cell zone of the lymph node E. When B cells up-regulate CXCR4 and migrate into the dark zone of the germinal center

A. When B cells cycle between the dark zone and the light zone of the germinal center

10.5 Multiple choice: Patients with the disease X-linked lymphoproliferative syndrome (XLP) lack expression of the small adapter protein SAP, which associates with receptors of the SLAM family. One characteristic of this disease is an inability of cytotoxic T cells to control infections with a virus, Epstein-Barr virus (EBV), that replicates in B cells. This defect in control of EBV results from: A. A defect in antibody responses to EBV due to impaired T cell help for B cells B. A defect in adhesion of cytotoxic T cells to EBV-infected B cells C. Impaired migration of activated B cells to the germinal center D. Impaired survival of activated B cells, normally induced by CD40 stimulation E. A defect in TFH differentiation, normally induced by ICOS on B cells binding to ICOS-ligand on TFH cells

B. A defect in adhesion of cytotoxic T cells to EBV-infected B cells

10.8 Multiple choice: In germinal centers, proliferating B cells undergo a process called somatic hypermutation, in which mutations are introduced into the V regions of the antibody heavy and light chain genes. When this process is complete after several weeks, the overall affinities of the antibodies produced are greatly increased compared to those present early in the primary response. The somatic hypermutation process leads to increased antibody affinity because: A. Mutations that decrease the antibody affinity lead to an arrest of B cell proliferation. B. B cells making higher affinity antibodies receive more help from TFH cells. C. Somatic hypermutations only take place in the sequences encoding the CDR1, CDR2, and CDR3 regions. D. Mutations that increase antibody affinity lead to an increased rate of B cell proliferation. E. The majority of nucleotide changes introduced by AID don't change the amino acid coding sequence.

B. B cells making higher affinity antibodies receive more help from TFH cells.

12.2 Multiple choice: In addition to Peyer's patches that resemble systemic lymph nodes, the intestinal epithelium also contains several thousand isolated lymphoid follicles. Unlike the organized secondary lymphoid tissues in the mucosal immune system, these lymphoid follicles: A. Contain mostly T cells and very few B cells B. Develop only after birth in response to colonization by commensal microbes C. Are not connected to the lymphatic system that drains to lymph nodes D. Have no M cells to deliver gut antigens to the lymphocytes in the follicles E. Are found only in the intestinal epithelium, and not in other mucosal epithelia

B. Develop only after birth in response to colonization by commensal microbes

10.21 Multiple choice: Neutralizing antibodies are effective at preventing infection or toxicity mediated by pathogens or their toxic products. In fact, nearly all vaccines currently in use function by eliciting neutralizing antibodies. One example is the tetanus vaccine, in which neutralizing antibodies are generated against an inactivated form of the tetanus toxin (i.e., the tetanus toxoid). The most important feature of a neutralizing antibody is: A. Having a high degree of multi-valency, such as being a pentamer or hexamer of immunoglobulin monomers B. Having high affinity for the antigen C. Being present at a high concentration in the circulation D. Being efficient at activating the complement cascade E. Having a long half-life in the body

B. Having high affinity for the antigen

12.19 Multiple choice: Reovirus is an enteric virus that infects mice by adhering to intestinal M cells and then using M cell transport to enter Peyer's patches. Mice that were orally inoculated with reovirus cleared the primary infection, and upon secondary challenge 21 days later, had no detectable virus in their Peyer's patches. In contrast, naive controls that did not receive the primary inoculation had >103 PFU of virus/mg of tissue following oral challenge with virus. The protective response induced by the primary oral inoculation would also be eliminated in: A. FcRn-deficient mice B. IgA-deficient mice C. IgM-deficient mice D. FcRI-deficient mice E. IgG-deficient mice

B. IgA-deficient mice

12.18 Multiple choice: Mice deficient in the enzyme MMP7, that cleaves prepro--defensin to the active -defensin, show an increased susceptibility to the enteric pathogen, Salmonella typhimurium. The cell type in the gastrointestinal (GI) epithelium most likely to express the highest levels of MMP7 is: A. Goblet cells B. Paneth cells C. M cells D. GI-resident macrophages E. Intraepithelial lymphocytes

B. Paneth cells

10.24 Multiple choice: The upper respiratory tract of many individuals is colonized by Streptococcus pneumoniae bacteria. Infections caused by these bacteria, including pneumonia, meningitis, otitis media (ear infections), and sinusitis, are thought to occur in individuals lacking protective antibodies. For many years, IgG was thought to be the major antibody class responsible for protective immunity to S. pneumoniae, due to the ability of anti-bacterial capsule IgG antibodies to opsonize the bacteria and promote phagocytosis. However, in addition to IgG, pneumococcal polysaccharides elicit robust IgA antibody responses. It was traditionally thought that these IgA antibodies functioned in neutralization, by blocking bacterial attachment to mucosal epithelial cells. It is now known that IgA antibodies, like IgG, can function as opsonins, to induce phagocytosis and killing of IgA-coated pathogens. This function of IgA antibodies depends on: A. The production of high affinity anti-bacterial IgA antibodies B. The dimeric form of IgA antibodies to bind to multivalent sites on the bacteria C. The ability of dimeric IgA binding to recruit and activate the complement cascade D. The presence of IgA-specific Fc receptors on neutrophils and macrophages E. The ability of IgA antibodies to efficiently cross the epithelial surface and enter the airways

D. The presence of IgA-specific Fc receptors on neutrophils and macrophages

11.4 Multiple choice: In response to an intracellular bacterial or viral infection, effector TH1 cells, macrophages, NK cells, and CD8 cytotoxic effector cells are all recruited to the site of infection. The coordinated recruitment of all of these cell types is orchestrated by: A. The secretion of the inflammatory cytokine IFN- in the tissue B. The action of TNF-alpha on the endothelial cells, leading to fluid leakage into the tissue C. The up-regulation of integrin ligands such as VLA-4 on the blood vessel endothelial cells D. The shared expression of chemokine receptors on these different cell types E. The shared expression of S1PR1 on these cells, recruiting them out of lymphoid tissues

D. The shared expression of chemokine receptors on these different cell types

10.15 Multiple choice: In humans, IgA is produced in copious amounts, estimated to be a rate of 3 g/day. Nearly all of the IgA secreting plasma cells are found in the gastrointestinal (GI) tract where the secreted IgA is transported across the GI epithelium into the lumen of the gut. There, this antibody protects the GI epithelium against intestinal pathogens. In contrast, none of the GI resident long-lived antibody secreting cells produce antibodies of the IgG class. The differential localization of long-lived antibody secreting cells producing IgA compared to those producing IgG is likely due to: A. Their interactions with TFH cells specific for pathogens that infect the gut B. The lack of germinal centers in the mucosal lymphoid organs C. The absence of S1PR1 expression on IgA-secreting plasma cells D. Their priming and differentiation in mucosal lymphoid organs E. Their inability to access the bone marrow compartment

D. Their priming and differentiation in mucosal lymphoid organs

11.25 True/False: The generation of optimal CD8 T cell memory following a primary infection requires CD4 T cell help for the responding CD8 T cells. This requirement for CD4 T cell help would not be completely replaced by supplying high levels of the cytokine IL-2 during the primary CD8 T cell response.

True

11.8 True/False: Nitric oxide and superoxide radicals are toxic compounds that induce substantial DNA damage. When released by activated M1 macrophages, these compounds cause damage to microbial pathogens and may also cause damage to host cells in the vicinity.

True

12.13 True/False: The TACI receptor on B cells, which binds to BAFF and APRIL, is important in IgA antibody secretion by B cells in the gastrointestinal lamina propria.

True

12.21 True/False: Oral tolerance to food antigens and immune tolerance to gut microbiota share the property that foreign antigens encountered in the gastrointestinal (GI) tract—food and commensal microbes, respectively—do not elicit immune effector responses. Yet, these processes differ in that commensal microbes will still elicit protective adaptive immune responses if they cross the GI epithelium and enter the body.

True

8.1 True/False: B and T lymphocytes develop from multipotent hematopoietic stem cells in the bone marrow. This process entails a continuum of development in which cells show progressive loss of multipotent potential, eventually becoming committed to a single lineage.,

True

8.14 True/False: Progenitor cells that migrate from the bone marrow to the thymus are not yet committed to the T cell lineage. T cell lineage commitment occurs as a result of signals received by the progenitor cell from thymic epithelial cells.

True

8.20 True/False: One feature of : T cells that identifies them as innate, rather than adaptive, lymphocytes is their ability to produce effector cytokines within hours of initial activation.

True

8.32 True/False: Some specialized subsets of alpha:beta T cells complete their development in the thymus and avoid negative selection, in spite of having T-cell receptors with high affinity for self-MHC complexes.

True

11.24 Multiple choice: Studies in mice have shown that resident memory cells (TRM) most often take up permanent residence in the tissue where the initial infection that produced those memory cells occurred. In this location, they are poised to respond rapidly should that infection re-occur in that same location. In contrast, central memory cells (TCM) are primarily found in secondary lymphoid organs, where they can be activated to proliferate and differentiate into effector cells when stimulated by antigen-bearing dendritic cells following re-infection. The third subset of memory cells, effector memory cells (TEM), are recirculating cells that can readily enter tissues at sites of inflammation or infection and are poised to rapidly respond to re-infection. The subset of TEM cells provides an important component of protective immunity to re-infection by the same pathogen because: A. They are the only memory cell subset that can produce effector cytokines within a few hours of antigen re-encounter. B. They are able to respond to S1PR1 and enter the blood circulation rapidly upon re-infection. C. They express the integrin E7 that binds to integrin ligands expressed on epithelial cells. D. They can protect against re-infection that occurs in a different site in the body than the primary infection. E. They can simultaneously express cytokines associated with all three effector T cell lineages.

D. They can protect against re-infection that occurs in a different site in the body than the primary infection.

8.10 Multiple choice: Individuals that overexpress the cytokine BAFF show increased susceptibility to autoimmune diseases such as Sjögren's syndrome, a disease that targets the exocrine glands that produce saliva, tears, and other bodily secretions. If one examined the circulating antibodies in these patients, one would expect to find: A. Increased development of B cells in the bone marrow B. A failure of receptor editing of immunoglobulin light chain genes in the bone marrow C. An increased rate of immature B cell export from the bone marrow D. Reduced B-cell receptor signaling following strong cross-linking of the receptor E. An increased number of circulating mature autoreactive B cells

E. An increased number of circulating mature autoreactive B cells

11.18 Multiple choice: The kinetics of a typical CD8 T cell response to an acute virus infection in mice is shown in Figure Q11.18. In this example, the virus is cleared by ~day 7 post-infection, and starting at ~day 10 post-infection, the majority of the virus-specific CD8 T cells die. The death of these virus-specific CD8 T cells is caused by: A. Lysis from the virus infection B. Engulfment and destruction by phagocytes in the body C. Destruction by cytotoxic T cells D. Natural killer cell lysis E. Fas-induced death or cytokine withdrawal

E. Fas-induced death or cytokine withdrawal

12.25 Multiple choice: IPEX syndrome is a genetic disease due to mutations that disrupt the function of an important transcription factor expressed in subset of CD4 T cells. Individuals with this disease generally begin showing symptoms shortly after birth. This disease is often fatal. One of the most prominent symptoms of IPEX is severe gastrointestinal inflammation accompanied by severe diarrhea. This transcription factor is most likely: A. RORt B. T-bet C. STAT3 D. NFB E. FoxP3

E. FoxP3

11.1 Multiple choice: While innate immune responses to all types of infections induce local inflammatory responses due to activation of blood vessel endothelial cells, some components of the innate response differ depending on the nature of the pathogen. In the case of intracellular bacterial or protozoan infections, tissue-resident dendritic cells and macrophages produce a cytokine that stimulates ILC cells to produce: A. IL-13 B. TNF-alpha C. IL17 D. IL22 E. IFN-gamma

E. IFN-gamma

12.16 Multiple choice: Mice lacking IL-15 or the IL-15R alpha chain have substantially reduced numbers of type b IELs, including both alpha:beta and gamma:derta T-cell receptor-positive subsets. Normal numbers of type b IELs can be restored in il15-/- mice by cell-type specific expression of IL-15 in: A. Thymic medullary epithelial cells B. Thymic cortical epithelial cells C. Dendritic cells D. CD8 alpha alpha+ T cells E. Intestinal epithelial cells

E. Intestinal epithelial cells

11.13 Multiple choice: Inflammatory bowel disease (colitis) is a CD4 T-cell mediated disease that can be transferred to naive mice by administration of effector CD4 T cells that home to the gastrointestinal tract and induce inflammation. Simultaneous administration of neutralizing antibodies to IL-12p40 can prevent the disease, as can neutralizing antibodies to IL-23p19. Disease symptoms can be exacerbated by administration of IL-23, but not of IL-12. These data strongly suggest that: A. Both TH1 and TH17 effector cells contribute to disease. B. TH1 cells producing INF- are the major causes of disease. C. IL-12p35 is a critical component of disease induction. D. The inducible IL-12R subunit is essential for disease induction. E. Neutralizing antibodies to IL-17 would prevent disease.

E. Neutralizing antibodies to IL-17 would prevent disease.

12.23 Multiple choice: IL-10-deficient mice develop spontaneous colitis, a disease due to chronic inflammation in the gastrointestinal (GI) tract. However, when these mice are housed in germ-free conditions, in which they lack all commensal microbes in their GI tract, no colitis was observed. In addition, one would expect germ-free IL-10-deficient mice to also show: A. Evidence of enhanced systemic immune activation compared to conventionally housed il10-/- mice B. Enlarged mesenteric lymph nodes compared to conventionally housed il10-/- mice C. Elevated numbers of FoxP3+ T cells in the lamina propria compared to conventionally housed il10-/- mice D. Increased production of IgG antibodies compared to conventionally housed il10-/-mice E. Reduced production of IgA antibodies compared to conventionally housed il10-/-mice

E. Reduced production of IgA antibodies compared to conventionally housed il10-/-mice

10.13 Multiple choice: In cell culture experiments, purified B cells expressing IgM can be induced to switch to producing IgE by stimulating them with an antibody to CD40 (a stimulatory antibody) plus the cytokine IL-4. In an individual undergoing an immune response, these signals would normally be provided by: A. Germinal center stromal cells B. Other B cells in the germinal center C. Follicular dendritic cells in the germinal center D. Any CD4 T cell in the same lymph node E. TFH cells in the germinal center

E. TFH cells in the germinal center

10.22 Multiple choice: IgM antibodies are much more efficient than IgG at activating the complement cascade. However, under certain circumstances, IgG antibodies will activate the complement pathway. One example of a situation in which IgG binding to its antigen will not trigger the complement cascade is when: A. The IgG antibodies bind to a multivalent soluble antigen in solution, such as a polysaccharide structure shed from a bacterial pathogen. B. The IgG antibodies bind to a viral capsid protein that is present in more than 100 copies on the viral particle surface. C. The IgG antibodies bind to a bacterial surface by recognizing a repetitive polysaccharide component of the bacterial capsule. D. The IgG antibodies are binding self-antigens such as chromatin released from dead cells. E. The IgG antibodies are neutralizing a bacterial toxin protein by blocking the receptor-attachment site on the toxin.

E. The IgG antibodies are neutralizing a bacterial toxin protein by blocking the receptor-attachment site on the toxin.

8.3 Multiple choice: B cell development in the bone marrow is an inherently wasteful process. Nearly half of the pro-B cells produced will die without progressing on to thenext stage of B cell development. This massive loss of pro-B cells is due to: A. The failure of many pro-B cells to up-regulate Pax5 and become committed to the B cell lineage. B. The inability of many pro-B cells to proceed with rearranging a VH to their rearranged DJH sequence. C. Large insertions of untemplated nucleotides into the rearranged gene by TdT. D. Detrimental DJH rearrangements on both alleles of the immunoglobulin heavy chain locus. E. The failure of the pro-B cell to make a complete immunoglobulin heavy chain protein.,

E. The failure of the pro-B cell to make a complete immunoglobulin heavy chain protein.

8.13 Multiple choice: Genetically inherited immunodeficiency diseases can result from defects in nearly any component of the immune response. The most severe forms of immunodeficiency occur when T cells are absent or non-functional. An individual with normal B cells, but an absence of T cells might have a defect in: A. RAG-1 or RAG-2 recombinase proteins B. Terminal deoxynucleotidyl transferase (TdT) C. Hematopoietic stem cells D. Bone marrow stromal cells E. Thymic stromal cells

E. Thymic stromal cells

10.6 True/False: Once B cells begin secreting antibodies, they cease dividing and have a life-span of only a few days.

False

11.16 True/False: In some infectious diseases, antibodies specific for the pathogen are not essential for clearing a primary infection with that pathogen, but are essential in preventing re-infection by the same pathogen. This protective role of pathogen-specific antibodies is not useful for any clinical applications.

False

12.5 True/False: Oral inoculation with rotavirus, an intestinal pathogen, induces adaptive immune responses that are initiated in gut-associated lymphoid tissue, such as mesenteric lymph nodes and Peyer's patches. The rotavirus-specific effector T cells that are generated in this response are never found in the circulation, but home directly from the lymphoid tissue to the epithelium without ever leaving the intestinal environment.

False

8.25 True/False: The repertoire of T-cell receptors, like that of antibodies, is formed by the random rearrangement of multiple gene segments that combine to generate the variable domain of each receptor subunit. The bias of T-cell receptors for binding to peptide:MHC complexes, rather than to all possible antigenic structures like antibodies, is simply the result of positive selection in the thymus.

False

8.34 True/False: T cell development in the thymus shares some similarities to a pipeline. As new progenitor cells enter the thymus, the most mature thymocytes are pushed out of the thymus to enter the circulation by a passive process.

False

8.7 True/False: Immature B cells expressing sIgM receptor emigrate from the bone marrow into the circulation. This is a passive process of cell diffusion, requiring no active signaling by the B cell.,

False

10.26 Multiple choice: Antibody-dependent cell-mediated cytotoxicity (ADCC) is an important effector mechanism in immunity to virus infections. This immune pathway has also been exploited for clinical applications. For instance, patients with various disorders, including rheumatoid arthritis and some B cell lymphomas, are treated with an antibody directed at CD20, a surface receptor expressed on all B cells. This antibody leads to the depletion of B cells from the patients by the actions of: A. Natural killer (NK) cells B. Cytotoxic CD8 T cells C. Cytotoxic CD4 T cells D. Activated macrophages E. The complement cascade membrane attack complex

A. Natural killer (NK) cells

10.20 Multiple choice: Infants born with the immunodeficiency disease X-linked agammaglobulinemia (XLA) have a block in B cell development, and fail to produce mature B cells. As a result, these infants lack the ability to produce antibodies. After birth, babies with XLA first begin to show symptoms of recurrent and persistent extracellular bacterial infections due to common environmental pathogens when they are 4-6 months of age. The reason these infants are healthy for the first 4-6 months after birth is because:Newborn infants have high circulating levels of maternal IgG at birth. A. Newborn infants are not exposed to bacterial pathogens for the first 4-6 months of life. B. Newborn infants are born with high circulating levels of complement proteins to protect them. C. Newborn infants are born with high circulating levels of antimicrobial peptides to protect them. D. Newborn infants are vaccinated against these common bacterial pathogens

A. Newborn infants are not exposed to bacterial pathogens for the first 4-6 months of life.

8.9 Multiple choice: Self-reactive B cells can be eliminated from the repertoire at several stages of B cell maturation, including immature B cells that have already emigrated from the bone marrow into the circulation. This latter stage of tolerance induction is critical because: A. Not all self-antigens are expressed or present in the bone marrow during B cell development. B. Immature circulating B cells are more sensitive to antigen stimulation than the developing B cells in the bone marrow. C. Receptor editing is not a perfect process and some self-reactive B cells may fail to be eliminated in the bone marrow. D. Circulating immature B cells do not encounter tissue-specific antigens in peripheral organs and tissues. E. Immature B cells are trapped in the bone marrow by strong B-cell receptor crosslinking.

A. Not all self-antigens are expressed or present in the bone marrow during B cell development.

12.7 Multiple choice: Analysis of human milk from lactating mothers shows that it contains IgA antibodies against infections that were recent (<3 weeks earlier) and those from the distant past (>1 year). These antibodies are directed against a host of organisms, including viruses, such as enteroviruses, herpes simplex viruses, respiratory syncytial virus, rubella, reovirus, and rotavirus. In addition, IgA antibodies against many bacteria are found in human milk, including those reactive to E. coli, Shigella, Salmonella, Campylobacter, Vibrio cholerae, H. influenzae, S. pneumoniae, Clostridium difficile, C. botulinum, and Klebsiella pneumoniae. IgA antibodies to the parasite Giardia and the fungus, Candida albicans, are also seen in human milk. Since most of these infections were localized in the gastrointestinal tract of the mother, these IgA antibodies ended up in breast milk by: A. Being transported from the lymph fluid in the breast tissue into across the breast epithelium into the secretory glands. B. The trafficking of germinal center B cells from the mother's mesenteric lymph nodes to the breast epithelium. C. The trafficking of gut-primed activated B cells from the mother's circulation into the lactating milk gland. D. The ability of gut-primed activated B cells to traffic to all secondary lymphoid tissues in the mother. E. The ability of activated B cells primed in the spleen to switch to IgA secretion after entering the mother's lactating milk gland.

C. The trafficking of gut-primed activated B cells from the mother's circulation into the lactating milk gland.

10.11 Multiple choice: The process of somatic hypermutation of antibody V regions sequences is initiated by the enzyme AID. This enzyme targets cytidine residues in the DNA sequence that are normally part of a G:C pair in the double-stranded DNA. Yet the hypermutation process generates mutations at both G:C and A:T base pairs of the original sequence because: A. Following AID action, a double-stranded DNA break plus chewing back of the ends occurs before re-ligation of the sequence. B. The error-prone polymerase repairs the sequence by inserting random nucleotides. C. There are two different pathways of repair target, one targeting G:C and one targeting A:T base pairs. D. B cells are the only cells to express the enzyme uracil-DNA glycoslyase (UNG). E. During active transcription both A:T and G:C base pairs are temporarily singlestranded.

C. There are two different pathways of repair target, one targeting G:C and one targeting A:T base pairs.

8.8 Multiple choice: Autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are characterized by high levels of circulating autoreactive 3 antibodies in the patient's circulation. An analysis of developing B cells in the bone marrow of these individuals might reveal that in some cases: A. Developing B cells become anergic in response to strong B-cell receptor crosslinking by multivalent self-antigens. B. Developing B cells are excluded from the B-cell follicles in the bone marrow and undergo rapid cell death. C. sIgM-positive developing B cells show premature down-regulation of RAG recombinase proteins prior to the onset of receptor editing. D. Hyperactive B-cell receptor signaling leads to rapid turnover of self-reactive developing B cells. E. Developing B cells have defects in allelic exclusion and express two different Bcell receptors on their surface.,

C. sIgM-positive developing B cells show premature down-regulation of RAG recombinase proteins prior to the onset of receptor editing.

10.28 Multiple choice: The W/Wv mouse strain is heterozygous for two different alleles of the gene encoding the growth factor receptor, c-kit, an important receptor expressed on hematopoietic progenitor cells in the bone marrow. The major defect in these mice is the absence of single lineage of hematopoietic cells. When these mice are challenged with larval Haemaphysalis longicornis ticks, they fail to become resistant to the ticks, in spite of generating high titers of anti-tick IgE antibodies. The cell type missing in the W/Wv mice is most likely:Natural Killer (NK) cells A. Eosinophils B. Tissue-resident dendritic cells C. Tissue-resident macrophages D. Tissue-resident mast cells

D. Tissue-resident mast cells

8.24 Multiple choice: Experiments performed with T-cell receptor transgenic mice identified the fate of developing thymocytes that failed positive selection. Based on these findings, examination of thymocytes in MHC class I-MHC class II-deficient mice (lacking all MHC class I and class II expression in the thymus) would show: A. A 100-fold decrease in total thymocytes numbers B. A block in T cell development at the CD4-CD8- double-negative stage C. Normal numbers and subsets of thymocytes and peripheral T cells D. Normal numbers of thymocytes, but no peripheral T cells E. A block in T cell development at the CD4+CD8+ double-positive stage

E. A block in T cell development at the CD4+CD8+ double-positive stage