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-1- Biology 347 Exam 1 February 12, 2008 Name__________________________________ I. Briefly describe the contributions (major findings) of the following to the development of immunology (3 points each, 18 points total) 1. S. Tonegawa and N. Hozumi page 114 of text. Provided first evidence that separate genes encode the V and C regions of immunoglobulins and that the genes are rearranged in the course of B-cell differentiation. 2. Ernest McCulloch and James Till Provided first evidence that hematopoietic stem cells existed that could give rise to progenitor cells to repopulate the white blood cells. 3. Lee Hood Demonstrated that kappa light chains consisted of as variable (V region) and constant region (C region) where the V region had accumulated mutations and the C region had not. Based on his studies, a twogene one polypeptide chain hypothesis was proposed to account for these findings. 4. Merrill Chase Text, page 6. succeeded in transferring immunity against the tubercculosis organism by transferring white blood cells between guinea pigs. One of the first to clearly demonstrate cellular immunity 5. Bruce Glick Text, page 6. Demonstrated that removal of the bursa in chickens resulted in deficiencies in humoral immunity (B cells and antibodies). 6. Edward Jenner Text page 2. The first to show that fluid from cow pox blisters injected into individuals would protect against small pox. The first to use the concept of vaccination. II. Short Answers (8 points each, for a total of 56 points. (Be concise and answer in space provided) 1. Describe Toll-Like Receptors (TLR) including cellular location, how TLR is activated, activated signaling pathways, proteins produced, and how these proteins kill pathogens. Text, page 63. TLR is a transmembrane receptor that is activated by pathogens (viruses, bacteria, fungi). Thus, pathogens are the ligands that activate the TLR. Activated TLR recruits adaptor proteins that signal through phosphorylation events (kinases) leading to the translocation of NFkB proteins from the cytoplasm to the nucleus where they act as transcription factors in the production of cytokines that bind to the pathogen, causing inflammation, migration of macrophages, neutrophils to the site of -2- infection and destruction of pathogens. The MAP kinase pathway is also activated and are translocated to the nucleus where they also act as transcription factors producing cytokines (some students may include NFkB causing cells to proliferate and MAPK to cause cells to undergo apoptosis) 2. Describe the mechanism(s) whereby Ig V region gene families undergo amplification and contraction. Need to indicate that there are V region genes for heavy chains (250-300-1,000, kappa light chains (250300), and lambda light chains (2). Thus, there are three Ig gene families. Within a gene family there is greater than 95% homology among the large number of V genes (especially for heavy and kappa chains). Expansion or contraction of V region genes occurs when homologous chromosomes line up incorrectly, a mechanism referred to as unequal crossing over occurs. The end result is to increase the number of gene family members (Amplification) on one chromosome and to decrease (Contraction) the number of gene family members on the other chromosome 3. Diagram the general structure of IgG, and describe how the structure relates to primary and secondary immune functions pages 85 to 89. Need to draw the structure and label as indicated on page 85. Need to inducate primary versus secondary responses involves Fab (involving both heavy and light chain) and secondary responses involve Fc portion of heavy chain. Secondary biological functions such as crossing placenta or binding complement. 4. Describe the end products when IgG is digested with (i) papain, (ii) pepsin, or (iii) treated with a reducing agent Text, page 86 5. List and briefly describe four (4) mechanisms for generating antibody diversity Text, page 123 they need to have 4 out of the 7 listed and briefly describe how the 4 generate antibody diversity. 6. Describe the mechanism(s) used by B lymphocytes to generate secreted and membrane bound IgM Text pages 130-133 7. Give the name and describe the process used by B lymphocytes to give rise to B cells expressing IgM with identical heavy and identical light chains -3- Text, page 121 allelic exclusion--need to describe how allelic exclusion works III. Multiple Choice (2 point each, 26 points total) 1. Rejection of a foreign skin graft is a function of A. destruction of virus-infected cells B. tolerance C. antibody-mediated immunity D. a secondary immune response E. a cell-mediated immune response 2. Tolerance is a _________ A. failure to make any antibodies B. defect in the cell-mediated immune system C. method of inducing autoimmunity D. ability of immune system to distinguish between self and non-self E. loss of resistance to infections 3. Different strains of mice respond differently to the same immunogen; namely, there is a high response in one strain and a low response in the other strain. Inability to generate a high response is due to a defect in: A. B cells B. antigen presenting cells C. V region genes D. D region gene segments E. MHC genes 4. Non-bony fish such as "Hag Fish" _____________. A. can generate a cellular but not a humoral immune response B. can generate a humoral but not a cellular immune response C. can generate both a cellular and humoral immune response D. none of the above 5. Which immunoglobulin heavy chain gene does not have DNA flanking sequences called switch regions upstream of CH segment? A. IgM B. IgD C. IgG D. IgA E. IgE 6. Which hypervariable region of heavy or light chains undergoes nucleotide changes as a result of DNA VDJ rearrangements? A. hypervariable region 1 B. hypervariable region 2 C. hypervariable region 3 D. hypervariable region 4 E. hypervariable region 5 7. Which immunoglobulin can cross the placenta? A. IgM -4- B. C. D. E. IgD IgG IgA IgE 8. Mice where RAG1 and RAG2 genes are knocked out: A. have a normal immune response system B. will not have a B cell immune response but will have a normal T cell immune response C. will not have a T cell immune response but will have a normal B cell immune response D. will not have a B nor T cell immune response E. none of he above 9. Recombination of immunoglobulin gene segments serves to A. promote Ig diversification B. assemble a complete Ig coding sequence C. allow changes in coding information during B cell VDJ rearrangements D. A and B are correct E. A, B, and C are correct 10. Kappa and lambda light-chains A. are coded by genes on the same chromosome B. can associate with only one type of heavy chain C. can both be expressed by the same B cell D. all of the above E. none of the above 11. B lymphocytes become immunocompetent A. following productive rearrangement of variable-region heavy-chain gene segments in germ-line DNA B. following productive rearrangement of variable-region heavy-chain and light-chain gene segments in germ-line DNA C. following class switching D. during affinity maturation E. following binding of T helper cytokines to their receptors on the B cells 12. Immunogenicity is determined by A. foreignness B. molecular size C. chemical composition D. all of the above E. none of the above 13. A kappa light chain type is the product of: A. kappa V region gene B. kappa D region gene segment C. kappa J region gene segment D. kappa C region gene E. A, C and D are correct