Faculty of MedicineDepartment of Laboratory Medicine, Children's and Women's Health Exam MOL3005 Immunology Thursday December 18 th 2008, 9.00 am - 1.00 pm ECTS credits: 7.5 Number of pages: 14 (including front-page and MCQ answers sheet) Examination support: Dictionary Contact person during the exam: Marit W. Anthonsen, 91897559 / 72573351 Exam results: January 19 th 2009 Examination results are announced on http://studweb.ntnu.no/ 1 Part I. Multiple choice questions (MCQ). This parts counts for 35% of the total points of the exam. A correct answer for a MCQ gives 1 point, except for MCQ 4, 5 and 7 which give 2 points each. One answer is the most correct. Answer the questions on separate MCQ answers sheet enclosed. Place only one cross for each question (the best alternative). 1. Cells of the innate immune system are specialized. Although several of them can ingest microbes, one cell type is found both undifferentiated in the blood and resident in tissues where they work as janitor (vaktmester) cells – eating particulate matter. What cell type best fit this description? A Macrophages B Neutrophils C Natural Killer Cells D Dendritic Cells E Granulocytes 2. Freunds adjuvant is a commonly used adjuvant when immunizing mice to improve antibody production. The so-called complete form (CFA) is composed of inactivated mycobacterial components emulsified in mineral oil. What best describes the mechanism behind the improved Ab production? A Effective antigen delivery to B-cells in the germinal center of lymph nodes B Improved degradation of the antigen by the cytosolic proteasome C Slow release of antigen and improvement of memory T-cell development D Slow release of antigen and TLR-initiated upregulation of co-stimulatory molecules of antigen presenting cells (signal 2) 2 3. Septic shock is a serious medical condition caused by decreased tissue perfusion and oxygen delivery as a result of infection. It can cause multiple organ dysfunction syndrome and death. What is causing the fatal organ failure? A Bacteria in the bloodstream B Defective innate immune response C Overwhelming immune response D Fungi in the bloodstream E Defective adaptive immune response 4. The lymphoid organs are organised tissue where lymphocytes (B-T cells) interact with non lymphoid cells (APC) and trapped antigen. They are divided into primary central and secondary peripheral organs and have different roles in immunity. What is the major function of the peripheral organs? A Provide the microenvironment for maturation of T and B cells. B Maximize contact between antigen and lymphocytes. C Produce antigen-specific lymphocytes from stem cells in response to antigen D Provide a site where memory T-cells reside to ensure a rapid response to antigen E Sequester antigen to minimize its damage to the body. 5. The immunoglobulin monomer is composed of several components. Which are these parts? A One heavy chain and two identical light chains B Two identical heavy chains and two identical light chains C Two identical heavy chains and one light chain D One constant part and two different variable parts 3 6. Allelic exclusion is a process that is unique to B- and T-cells. Why is it important for B-cells to exert (have) allelic exclusion? A Allelic exclusion ensures that a B cell can recognize only one antigen and give increased antibody diversity B Allelic exclusion ensures that a B cell can recognize several antigens and give increased antibody diversity C Allelic exclusion ensures that a B cell can recognize only one antigen and enables control of antibody specificity D Allelic exclusion ensures that a B cell can produce high affinity antibodies towards several antigens 7. Naïve B cells require several signals in order to become activated. Which are these signals? A Signal 1 from antigen through the B cell receptor and signal 2 from CD4 positive T-cells B Signal 1 from antigen through the B cell receptor and signal 2 from CD8 positive T-cells C Signal 1 from CD4 positive T-cells and signal 2 from follicular dendritic cells D Signal 1 from CD4 positive T-cells and signal 2 from cytokines produced by macrophages E Signal 1 from antigen through MHC molecules and signal 2 from cytokines produced by macrophages 8. The germinal center reaction is an important part of the antigen-dependent development of B cells. Through which mechanisms does antigen-dependent development of B cells occur? A Clonal expansion, class switching, somatic hypermutation and differentiation B Clonal expansion, antibody production and activation of the B cell C Somatic hypermutation, immunoblobulin rearrangement and activation of the B cell D Clonal expansion, proliferation, class switching and allelic exclusion 4 9. B-cells can produce five different classes of antibodies. Antibodies belonging to the different classes have different effector mechanisms. Transport of antibodies from mother to the fetus (transcytosis) is important to protect the child against disease during the first months after birth. Which one of the following sentences describes this situation most accurately? A Transportation of IgM and IgG to the fetus provides the child with antibodies that, through opsonization and neutralization, may protect against several diseases B Transportation of IgG and IgE to the fetus leads to protection of the child through different effector mechanisms towards the same antigens that the mother has generated antibodies towards C Transportation of IgM to the fetus provides the child with antibodies that, through opsonization and neutralization, may protect against several diseases D Transportation of IgG to the fetus leads to protection of the child through different antibody effector mechanisms towards the same antigens that the mother has generated antibodies towards 10. Immunological memory is important for an effective vaccine. Which one of the following sentences describes the underlying mechanisms for this most accurately? A Macrophages and B cells have developed optimal effector mechanisms towards the antigen contained in the vaccine and can during an infection with this antigen respond faster and more effectively B T -and B-cells have developed effector mechanisms towards the antigen contained in the vaccine and can during an infection with this antigen respond fast and effectively to prevent disease C T -and B-cells have developed effector mechanisms towards a certain virus or bacteria and can prevent us from infection D NK cells, T -and B-cells have developed effector mechanisms towards the antigen contained in the vaccine and can during an infection with this antigen respond faster and more effectively 11. The internal immune system is mainly enforced by leukocytes, the leukocytes have different half-lives and are constantly generated, about 10 11 each day in a human adult. Where are they generated? A All leukocytes originate from the bone marrow B All leukocytes except T cells originate from the bone marrow C B cells originates from the bone marrow, T cells from the thymus and innate immune cells are formed throughout the body D Leukocytes originate from most tissues in the adult body E Innate immune cells originate from the bone marrow, lymphocytes from lymphoid tissue 5 12. An essential part of the innate immune system is phagocytosis followed by destruction of the phagocytosed particle/microbe followed by antigen- presentation. What cells are considered professional phagocytes? A Granulocytes, monocytes, macrophages, dendritic cells B Granulocytes, monocytes, macrophages, dendritic cells, B cells C Granulocytes, monocytes, macrophages, B cells D Antigen presenting cells E All innate immune cells 13. The primary defense against microbes is accomplished by innate immune cells whereas the secondary response is based on the adaptive immune cells. How are these similar? A They are both antigen specific B They both depend on dendritic cells C They are both based on pre-synthesized proteins that are quickly released D They both respond better to live than to killed virus E They are governed by the same cytokines 14. Natural Killer (NK) cells are innate immune cells with important functions against viral infections. What is the main mechanism of recognition of infected cells? A Viral epitopes presented by non-classical MHC molecules B Through by-stander effects initiated by neighbouring activated dendritic cells C By cross-presentation of viral epitopes by follicular dendritic cells in the lymph nodes D By specific anti-viral antibodies on the infected cell surface E By binding of viral epitopes to Toll-like receptors (TLRs) on the NK cell 6 15. Apoptosis is physiological cell death genetically encoded and regulated. The main pathways of extrinsic apoptosis (mediated by cytotoxic cells) are receptor-mediated and granule exocytosis-mediated apoptosis. How are these different? A NKcells use granule mediated, whereas cytotoxic T cells use receptor mediated B Receptor mediated apoptosis requires susceptibility by the target cell, whereas any cell is a target of granule mediated apoptosis C Receptor mediated apoptosis is used against cancer cells, whereas virus infected cells are killed by granule mediated apoptosis D Receptor mediated apoptosis is the primary mechanism, whereas granule- mediated is the secondary mechanism based on preformed antibodies 16. Cross-presentation is a feature found only in dendritc cells. What is the sequence of events? A Antigen/microbe/cell is phagocytosed, degraded in lysosomes, loaded onto MHC class II and transported to the surface B Antigen is translated to protein from phagocytosed microbial mRNA in the cystosol, transported into ER, loaded onto MHC class I and transported to the surface C Antigen/microbe/cell is phagocytosed and broken down in lysosomes, antigens are transported to cytosol for proteosomal degradation, transported to ER, loaded onto MHC class I and transported to the surface D Antigen/microbe/cell is phagocytosed, transported to ER, degraded by proteasomes, loaded onto MHC class I, and transported to the surface E Antigen/microbe/cell is phagocytosed, degraded in lysosomes, loaded onto MHC class I and transported to the surface 17. During the intracellular phase viruses are detected by cytosolic immune proteins as well as by cytotoxic T cells recognizing viral peptides presented on MHC class I. Why are live viruses better than killed viruses as vaccines? A Killed viruses are degraded in lysosomes and are therefore inefficiently presented by the MHC class I pathway B Killed viruses are recognized and destroyed faster since they can not evade immunity C Killed viruses do not activate complement D Only replicating viruses contain ligands that activate the Toll-like receptors in antigen presenting cells E Live viruses infect non-immune cells, whereas killed viruses only enter phagocytes 7 18. Autoimmunity is an inappropriate adaptive immune response against self proteins. What is a likely mechanism in breakdown of tolerance? A Primary targets of autoimmunity are cells that express high levels of tissue antigens B Cells that leave their designated tissues and enter other tissues can elicit autoimmunity C Cells chronically infected by viruses can not longer dampen immune responses and therefore promote a break in tolerance to its own antigens D Defects in the apoptotic machinery allows self-reactive adaptive immune cells to proliferate E Repeated injury and the following inflammation can cause autoimmunity 19. The conversion from a normal cell to a tumor cell is caused by genetic changes in the cell. One major class of genes involved in this process is called tumor suppressor genes. Which description fits best to this class of genes? A The gene product is inhibiting cell cycle progression/proliferation or promotes apoptosis B Overexpression of the gene leads to uncontrolled proliferation C The gene product is involved in detection of DNA-damage or DNA-repair D “Gain of function” mutations of the gene promote cancer development 8 20. The immune system can specifically identify tumor cells on the basis of their expression of tumor-specific or tumor-associated antigens. Which description fits best for the latter type of antigens? A Encoded by mutations in tumor cells that generate altered cellular proteins B Encoded by genes exclusively expressed by tumor cells C Encoded by genes expressed by normal cells at low levels, or by genes normally expressed only during fetal development D Encoded by oncogenes E Encoded by tumor suppressor genes 21. The immune system can both protect the host against tumor development AND promote tumor growth. Which cell types are involved in the latter phenomenon? A Suppressor T-cells and M2 macrophages B NKT cells C CD8+ T cells and NK cells D B-cells and M1 macrophages E Dendritic cells 22. Rituximab is a monoclonal anti-CD20 antibody used in the treatment of CD20+ B- cell non-Hodkin’s lymphoma. How can this antibody prevent tumor progression? A By tagging the tumor cells for destruction by activated cytotoxic T-cells and/or NKT cells B By tagging suppressor T-cells for elimination by NK cells C By tagging the tumor cells for destruction mediated by the complement system and/or by inducing antibody-dependent cell-mediated cytotoxicity D By targeting toxins to the malignant cells 9 23. Members of the immunoglobulin superfamily are mainly molecules with a receptor function. Which of the following molecules have the MHC II as its natural ligand? A CD2 B CD3 C CD4, TCRαβ D CD28 24. Thymus is a central lymphoid organ for cellular maturation and selection Which of the following cells are negatively selected in the thymus? A Autoreactive B-cells B Autoreactive NK-cells C T-cells recognizing allogeneic MHC D T-cells with strong affinity to autologous MHC 25. Immune responses in the adaptive immune system have to be turned on, and off again when the adequate reaction is fulfilled Which statement below is correct? A CTLA-4 is expressed on activated B-cells B CTLA-4 gives a negative signals to B-cells C CTLA-4 on T-cells competes with CD28 for binding to B7 on B-cells D CTLA-4 gives an activation signal to T helper cells 10 26. The biological function of HLA II molecules is to present antigens to T helper cells What is correct of the statements below? A Class II molecules are expressed on B-cells B Class II molecules are expressed on resting T-cells C HLA-DR-antigens have monomorphic β-chains D Allelic exclusion is a characteristic of HLA molecules 27. Important function of NK-cells is to kill virus-infected cells and tumor cells What is correct of the statements below: A NK-cells use their KIR receptors for killing target cells B NK-cells make memory cells C NK-cell killing is stimulated by HLA molecules D NK-cells are part of the innate immune system 28. HLA-molecules are of importance in organ and bone marrow stem cell transplantation Which of the following conditions are relevant in transplantation? A HLA class I molecules are only weak (minor) transplantation antigens B Only matching for HLA class II molecules is necessary in bone marrow transplantation C Blood group O kidneys can not be given to a blood group A recipients D Crossmatch test should always be performed before allotransplantation 29. Septic shock may develop when bacterial components are recognized by dendritic cells and macrophages. Which two proinflammatory cytokines are rapidly elevated during early phases of bacterial septic shock? A TNF-α and IL-1β B IL-2 and TNF-β C IL-4 and IL-5 D TNF-β, TGF-β 11 30. The NALP-3 inflammasome is assembled in the cytosol in response to danger signals and plays an important role in the regulation of IL-1β. What is the consequence of activation and assembly of the NALP-3 inflammasome? A pro-IL-1β is synthesized B pro-Caspase-1 is cleaved into active Caspase-1, which cleaves pro-IL-1β into active IL-1β C IL-1R antagonist (IL-Ra) is produced which blocks the IL-1 receptor, inhibiting binding of IL-1β to its receptor D Pro-IL-1 β is rapidly degraded 31. The IL-2 receptor occurs in three forms that exhibit different affinities for IL-2. These include the low affinity monomeric IL-2Rα (also known as TAC antigen or CD25), the intermediate affinity dimeric IL-2Rβγ, and the high-affinity trimeric IL- 2Rαβγ. Which cells typically express the high-affinity trimeric IL-2Rαβγ? A Resting CD8+ T cells B Neutrophils and macrophages C Activated CD4+ and CD8+ T cells D Naïve B cells 32. Two subpopulations of T H cells, designated T H 1 and T H 2, can be distinguished in vitro by the cytokines they secrete. Which cytokines are typically secreted by the T H 2 subset? A IFN-γ, TNF-β, IL-2 B IL-4, IL-5, IL-10 C IL-12, IL-6, IL-1 D IL-8, RANTES, MIP-1α 12 13 Part II. Essay questions. This parts counts for 65% of the total points of the exam. Examination question 1 (15 points). Cytokines are low-molecular weight regulatory proteins secreted by white blood cells and various other cells in response to stimuli. a. Briefly describe what determines whether a given cytokine will affect a given cell. How do cytokine that display an autocrine and paracrine mode of action differ? b. The biological activities a cytokine may include pleiotropy, redundancy, synergy, antagonism and cascade induction. Describe these terms briefly. c. The cytokine environment determines the development of T H 1 and T H 2 subsets. Which key cytokines determine the T H 1/T H 2 balance and what are the functional differences between T H 1 and T H 2 cells? Examination question 2 (20 points). Complement is important in many immune reactions. Describe the effects of central complement components. Examination question 3 (20 points). Describe the mechanism underlying V(D)J-rearrangement of immunoglobulin genes (preferentially including a drawing/figure). What is the result of rearrangement, where and at which levels of the B cell development does it occur? Examination question 4 (10 points). a. Briefly describe how tumor cells evade the immune system b. How can NK cells recognize and attack tumor cells?