Immunology MIMM-314 MID-TERM II EXAMINATION. 1 hour between 8:30 a.m. - 10:00 a.m. McIntyre Medical Rm 504 (Martin Amphitheatre)

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1 GROUP (Version) 1 Annotated version April 8, 2011, RGEP DEPARTMENT OF MICROBIOLOGY AND IMMUNOLOGY Immunology MIMM-314 MID-TERM II EXAMINATION Course Coordinator: Dr. Roger Palfree Date: Thursday, March 17, 2011 Time: Place: 1 hour between 8:30 a.m. - 10:00 a.m. McIntyre Medical Rm 504 (Martin Amphitheatre) * * * * * * * * * ******************** * * * * * * * * * DO NOT TURN THIS PAGE UNTIL YOU ARE TOLD TO DO SO Instructions: 1. Multiple choice questions: a) Our Type I and Type II multiple choice questions are to be answered on the Answer Sheet provided. Do not fold or bend the sheets. b) Print your name and student number and indicate your exam group number (see top of page) on the front of the Answer Sheet. c) Read each question and its numbered answers. When you have decided which alternative is the BEST, mark the whole of the corresponding oval space (bubble) on your answer sheet. Avoid making any stray marks outside the oval. d) Do not answer with more than one mark for any question, otherwise the computer will reject your sheet. If erasing, erase completely. 2. Questions requiring written answers: There are no questions requiring written answers on this midterm exam. 3. Marking will be on the basis of +1 mark for a correct answer; questions unanswered or wrongly answered will be tallied as "0" when totalling your score. 4. DURING THE EXAM: NO PART OF THIS EXAMINATION MAY BE TAKEN OUT OF THE EXAM ROOM UNDER ANY CIRCUMSTANCES. (But you may keep it and take it with you after the exam). The Examination Security Monitor Program detects pairs of students with unusually similar answer patterns on multiple-choice exams. Data generated by this program can be used as admissible evidence, either to initiate or corroborate an investigation or a charge of cheating under Section 6 of the Code of Student Conduct and Disciplinary Procedures. 1

2 TYPE 1 QUESTIONS ONLY ONE OF THE CHOICES IS CORRECT - MARK 1, 2, 3, 4, or 5 1. Which of the following statements is correct? 1. A failure of recognizing self-peptide/mhc complexes induces death of CD4-CD8- thymocytes. 2. Mice lacking expression of MHC class I molecules fail to produce CD4+CD8- thymocytes. 3. AIRE is an enzyme that controls the expression of MHC molecules by thymic epithelial cells. 4. T lymphocytes can express two different TCR restricted to two different self-mhc molecules. 5. Mature naïve CD4+ T cells transferred into MHC class II deficient mice will not survive. SF Ans: 5 2. Which of the following would you expect to find in mice in which all T cells express a transgenic TCR specific for a peptide of a protein expressed only in male mice? 1. In male mice, thymocytes die at the DN stage and no mature transgenic T cells are found in the peripheral lymphoid organs. 2. In female mice, thymocytes are not positively selected because female mice do not express the protein and no mature transgenic T cells are found in the peripheral lymphoid organs. 3. In male mice, thymocytes die at the DP stage and no mature transgenic T cells are found in the peripheral lymphoid organs. 4. In female mice, thymocytes are positively selected but mature T cells do not survive in peripheral lymphoid organs because female mice do not express the protein. 5. None of the above SF Ans: 3 3. B cells that have proliferated after an initial antigen-specific interaction with a T cell in the T-cell area of a lymph node migrate first to 1. the marginal zone to form a primary focus 2. the blood to form a germinal center 3. the bone marrow where they differentiate into long-lived plasma cells 4. medullary cords to divide further before becoming short-lived plasma cells 5. none of the above SF Ans: 4 4. Which of the following best describes a germinal center? 1. a site whose function is to maximize the encounter between antigen-binding B cells and helper T cells 2. a site where reside T cells 3. a site where centrocytes with the highest-affinity receptors for antigen are selected 4. a site where immature B cells specific for self-antigens die by apoptosis 5. a site where reside B cells that have their Ig genes in germline configuration SF Ans: 3 5. The poly-ig receptor is involved in 1. The transfer of IgG across the placenta. 2. Opsonization of IgG coated bacteria. 3. The release of histamine by mast cells. 4. The transcytosis of IgA across epithelia. 5. None of the above SF Ans: 4 (Originally answer 5 was indicated as correct, which would only be right if the statement 4 wasabout monomeric IgA. As written, answer 4 is clearly the correct one. ) 2

3 ONLY ONE OF THE CHOICES IS CORRECT - MARK 1, 2, 3, 4, or 5 6. Which of the following Fc receptors found on mast cells promotes the release of cytoplasmic granules? 1. Fc(alpha)RI 2. Fc(gamma)RI 3. Fc(gamma)RII-B2 4. Fc(gamma) RII-B1 5. Fc(epsilon)RI SF Ans: 5 7. Which of the following are true regarding naïve T cells in lymph nodes? 1. Gain the expression of the CD45RA isoform 2. Require antigen stimulation in non-lymphoid tissue prior to lymph node entry 3. Are poor responders to CCL22 4. Bind to MAdCAM-1 expressed on the mucosal endothelium 5. Downregulate CD44 after TCR engagement CP Ans. 4 (There were several who criticised this question as confusing. We now have a response from Dr. Piccirillo: This question was not properly verified. A mark should be granted. I will deal with it when working out the final grades.) 8. Immune responses to commensal microbes in the gut can result in the following: 1. A Th17 response to gut pathogens like Citrobacter Rodentium 2. A Th2 response to extracellular, Gram negative bacteria 3. An IL-10-secreting Tr1 response to intestinal bacteria 4. Foxp3 + Treg responses to dietary antigens 5. All of the above CP Ans Which of the following is true regarding co-stimulation to T cells: 1. Memory and naïve T cells have identical co-stimulatory requirements. 2. CD40/CD40L interactions result in activating signals in T cells only. 3. CTLA-4 and CD28 are constitutively expressed on CD4 + T cells. 4. CD28 has the same affinity for B7.1 than CTLA CD4 + T cells activate APC to upregulate 4-1BBL for optimal CD8 + T cell responses. CP Ans Adaptive immunity, unlike innate immunity, provides the host with the following features: 1. Rapid generation of immune effector mechanisms for the control of infections. 2. Receptor-mediated recognition of self and non-self antigens 3. The capacity to control pathogen growth and infections. 4. Long-lived, polyclonal memory responses 5. The exclusive capacity to produce interferon alpha CP Ans. 4 (Supplied originally with answer 2 as correct. Obviously a mistake.) 11. The functions of LFA-1 include: 1. Binds ICAM-1 but not ICAM-2 2. Its activity is not affected by TCR signaling following antigen stimulation. 3. LFA-1 enables T cell adhesion on HEV 4. LFA-1/ICAM-1 interactions are always of high affinity. 5. Binding to ICAM-1 only after T cell receptor engagement. CP Ans. 3 3

4 ONLY ONE OF THE CHOICES IS CORRECT - MARK 1, 2, 3, 4, or Th2 cell-mediated immunity is characterized by: 1. Macrophage activation and elimination of intracellular pathogens found in cytosol or vesicles. 2. The concurrent generation of Th17 effector T cells. 3. Production of LT-α 4. Provision of help to antigen-specific B cells 5. TNF-α dependent activation of antigen-presenting cells CP Ans Protective immunity against Leishmania can be achieved by: 1. Activation of infected macrophages by IFN-γ. 2. Induction of IL-10 production. 3. Potentiation of CD4 + regulatory T cell activity 4. Activation of antigen-specific B cells 5. All of the above. CP Ans: 1 (I am awarding everyone an additional mark for this defective question. I cannot improve on your respected TA s comments: In this question, protective immunity is completely ambiguous. In his lectures he spends a long time telling the students how if you potentiate IFN-gamma axis in Leishmania major infected mice, they are RESISTANT to infection, but susceptible to reinfection. If you potentiate Fox-P3/IL-10 axis, they are SUSCEPTIBLE to infection, eventually control it and maintain the infection in a granuloma and are RESISTANT to reinfection because they develop a memory response. In my mind protective immunity is a memory response, and this is unclear and was presented to the students in a completely different manner than how the question was asked, which leads to confusion.) Name a cytokine required to be present, for IgE production by B cells. 1. IL-2 2. STAT-6 3. Il-4 4. Il Il-7 RA Ans: In serum sickness the immune complexes are formed because 1. there is an excess of antigens as opposed to antibodies 2. There is an excess of antibodies as opposed to antigens 3. There are similar amounts of antigens and antibodies 4. There is an excess of peptides as opposed to T cell receptors 5. There is an excess of T cell receptors as opposed to peptides RA Ans: 1 4

5 TYPE II QUESTIONS ONE OR MORE OF THE SUGGESTED ANSWERS OR COMPLETIONS IS/ARE CORRECT A + C = 1 B + D = 2 A + B + C = 3 D = 4 E = In a mouse of MHC b genotype irradiated and reconstituted with bone marrow cells from a mouse of MHC (a x b) genotype, it is possible to find: A. mature T cells tolerant to MHC molecules of genotype b but not a B. mature T cells restricted to MHC molecules of genotype b but not a C. mature T cells restricted to MHC molecules of genotype a and b D. mature T cells tolerant to MHC molecules of genotype a and b E. mature T cells expressing MHC molecules of genotype b but not a SF Ans: B+D = Which of the following cell types mediates positive selection of thymocytes that will express a TCR restricted to self-mhc class II molecules? A. Thymic cortical epithelial cells expressing only MHC class II molecules B. Thymic medullary epithelial cells expressing MHC class I and class II molecules C. Thymic medullary epithelial cells expressing only MHC class II molecules D. Thymic cortical epithelial cells expressing MHC class I and class II molecules E. Dendritic cells expressing MHC class I and class II molecules SF Ans: D = Which of the following molecules expressed by B cells is (are) necessary for their activation in response to a T-dependent antigen? A. CD40 B. IL-4 C. IgM D. CD45 E. IL-7 SF Ans: A +C = Which of the following statements is true? A. At high concentrations, TI-2 antigens can induce the proliferation and differentiation of B cells in absence of specific antigen binding to surface Ig B. TI-1 antigens can induce the production of IgM and IgG antibodies. C. TI-2 antigens induce antibody responses in infants. D. Bacterial lypopolysaccharide (LPS) is an example of a TI-1 antigen. E. TI-1 antigens are efficient inducers of affinity maturation. SF Ans: D = Which of the following statements is (are) correct? A. The complement receptor CR1 on the erythrocyte surface has an important role in the clearance of immune complexes from the circulation. B. For many Fc receptors, ligand recognition is mediated by the alpha chain while signal transduction is mediated by the gamma chain C. Large parasites are more usually attacked by eosinophils D. Free immunoglobulin molecules bind most Fc receptors with very low affinity and cannot cross-link Fc receptors. E. All of the above. SF Ans: E = 5 5

6 A + C = 1; B + D = 2; A + B + C = 3; D = 4; E = Which of the following Ig Fc receptors transduces an inhibitory signal? A. Fc(alpha)RI B. Fc(epsilon)RI C. Fc(gamma)RIII D. Fc(gamma)RII-B1 E. None of the above SF Ans: D = Which of the following statements are true regarding T cell-dependent B cell responses? A. Is unaffected in LFA-1 deficient mice. B. Generally insensitive to IL-4 produced by NK-T cells. C. Does not require cognate T:B cell interactions D. Generally normal in CD40L deficient mice. E. None of the above CP Ans: E = Which of the following is/are true regarding CD4 + Foxp3 + regulatory T cells A. Can differentiate extra-thymically from non-regulatory T cell progenitors. B. Their development is abrogated in IPEX. C. Can be induced from naïve T cells through the action of TGF-β1. D. Suppress Th1 or Th2 mediated immune responses. E. All of the above CP Ans: E = Activated Th1 cells can eliminate intracellular pathogens using which of the following? A. CD40L-mediated activation of TB-infected macrophages. B. By secreting GM-CSF and favoring the development of bone marrow progenitors. C. TNFα -mediated signaling in TNFR on infected APC D. By upregulation of NO production E. All or none of the above. CP Ans: E = 5 (Although I expect most of you interpreted D as talking about the interacting system, a few felt that it was to be interpreted as talking about what the T cell does itself. Yet again, the challenge of constructing clear multiple choice questions was not sufficiently met. I will allow A+B+C = 3 also.) 25. IL-23 is: A. An immunosuppressive cytokine. B. A potent inhibitor of APC maturation. C. Produced by Treg cells but not Th2 cells. D. Expressed by dendritic cells and supports the expansion and survival of Th17 cells. E. None of the above. CP Ans: D = Which is true regarding CD4+ T helper (Th) cell differentiation? A. Is influenced by the ability of IL-4 to induce GATA-3 expression in T cells B. Is not affected by the route of infection. C. Can result in RORγT induction in CD4 + T cells if TGF-β and IL-6 are present during T cell activation. D. Is unaffected by the nature of the pathogen. E. All of the above. CP Ans: A+ C = 1 6

7 A + C = 1; B + D = 2; A + B + C = 3; D = 4; E = Which of the following is true regarding a primary infection to virus A in the gut? A. Is influenced by prior infection to virus B sharing the same antigenic determinants as virus A B. Leads to the production of virus A specific, effector memory T cells located in the gut. C. Virus A specific, effector memory CD4 + T cells are CD45RO + and CCR7 - and reside in the infected gut. D. Subsequent infections with virus B result in a greater magnitude in virus B specific, effector memory T cells responses. E. All of the above CP Ans. E = 5 (The requested revision to indicate clearly that virus B was the same as described in answer A was apparently overlooked. But I announced that it was to be interpreted that way during the exam. The two students who took the exam elsewhere, and did not hear the announcement chose the next best answer: A+B+C, so I am allowing both 5 and 3 as answers. ) 28. Which statement is true about IL-12? A. Is produced by activated Th17 cells B. Extracellular pathogens induce IL-12 production, which consequently promotes IgG1 production. C. Can activate NK1.1 T cells to produce IL-4. D. Its production is not affected by TLR signals. E. Promotes IFN-γ production in NK and T cells. CP Ans: E = Which of the following is/are true A. The main function of IgE molecules is to bind pathogenic peptides B. For the type IV hypersensitivity reaction to be effective the response must occur within minutes C. There are 2 types of IgE receptors at the surface of monocytes D. The expression of a dysfunctional filaggrin protein inside the keratinocytes increases the risk of developing autoimmune diseases E. It seems that hygienic environments increase the risk of development of atopic diseases RA Ans: E = Which of the following is/are true A. Upon their activation eosinophils release significant amounts of Major basic proteins, Eosinophil cationic proteins and Eosinophil-derived neurotoxins B. Phagocytosis plays an important role in the type II Hypersensitivity C. Basophils express IgE receptor molecules at their surface D. Helminths release major quantities of histamine once attacked by mast cells E. Basophils play a major role in the type IV hypersensitivity RA Ans: A+B+C = 3 7

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