Name:______________________________________Question 1: _____________________Question 2: _____________________Question 3: _____________________Question 4: _____________________Question 5: _____________________Question 6: _____________________Question 7: _____________________Question 8: _____________________Question 9: _____________________Question 10: _____________________Question 11: _____________________Total Score: _____________________Question 1Question 2Mouse 1:Gender:MHC:Mouse 2 (two pairs of possibilities)):Gender in option 1: Gender in option 2:MHC in option 1: MHC in option 2:Question 3A) Complement subserves many functions. Please list three functions mediated by the complement cascade and its byproducts.B) What aspect of the IgM molecule facilitates its ability to initiate the classical complement pathway?Question 8HST175 Final Exam 12.13.04 Good luck and thanks for all your hard work this semester! Name:______________________________________ Question 1: _____________________ Question 2: _____________________ Question 3: _____________________ Question 4: _____________________ Question 5: _____________________ Question 6: _____________________ Question 7: _____________________ Question 8: _____________________ Question 9: _____________________ Question 10: _____________________ Question 11: _____________________ Total Score: _____________________Harvard-MIT Division of Health Sciences and TechnologyHST.176: Cellular and Molecular ImmunologyCourse Director: Dr. Shiv PillaiName: Question 1 a. Explain in a stepwise fashion how signals from the T cell receptor induce NFAT activity in the nucleus. Explain briefly how you think FK506 /Tacrolimus (an immunosuppressive drug) works.Name: Question 2 A friend of yours at Yale is also taking immunology this semester. Intrigued by the concept of minor histocompatibility antigens, he drops his previous undergraduate thesis and starts working on the H-Y antigen. He first takes skin from a male H-2b mouse and grafts it onto a female H-2b mouse. The graft is slowly rejected. He waits a week, regrafts skin from the same male H-2b mouse onto the same female H-2b mouse and finds that the graft is rejected slightly faster this time. He then collects CD8+ T cells from this female H-2b mouse and purifies cells that recognize H-2Db: H-Y complexes. He clones the α and β TCR genes from one of these T cells and makes a transgenic mouse that expresses the H-2Db-restricted, H-Y-specific TCR on the RAG-/- background. He then breeds this mouse onto two different MHC backgrounds: H-2b or H-2d. Unfortunately, he went into lab the day after the Harvard-Yale game, and being a bit hung over, he mixed up all of his cage cards so he doesn’t know which cages contain H-2b mice and which contain H-2d mice. Furthermore, having never worked with mice before, he doesn’t know how to determine the sex of a mouse. Determined to avoid embarrassment in lab, he calls you and asks for help. He provides you with thymocyte FACS profiles for three of his mice and asks you to help him determine the MHC background and sex of these three mice. Please help your poor Yale friend and determine the sex and MHC background of these mice, indicating any ambiguities that may be present. Briefly (1-2 sentences) explain to him how you were able to determine the sex and MHC background of each mouse from the FACS plots he provided you. Purify H-2Db-restricted, H-Y-specific CD8+ T cells Clone TCR genes from one of these T cells Make TCR transgenic mouse on RAG-/-background Breed transgene onto H-2b or H-2d MHC backgrounds (mice are still RAG-/-)Skin graft Mouse 1 Mouse 2 QuickTime™ and aTIFF (LZW) decompressorare needed to see this picture. A) Mouse 1: Gender: MHC: B Gender in option 1: Gender in option 2: ) Mouse 2 (two pairs of possibilities)): MHC in option 1: MHC in option 2:Name: Question 3 A) Please provide a diagram of deletional VDJ signal and coding joint formation (include a diagram of the important parts of the locus before VDJ recombination, the two intermediates, and the end products. Please indicate any regions which are altered in the process). B) You have just examined a male infant with recurrent oral candidiasis (thrush) and non-pyogenic lung infections. Another male sibling received a bone marrow transplant four years ago after presenting in a similar manner. Serum immunoglobulins are normal, but the child lacks CD4 T cells, CD8 T cells, and NK cells. The diagnosis of severe combined immunodeficiency is made. What do you think may be the molecular defect in this child?Name: Question 4 Viruses have been shown to evade every aspect of innate and adaptive immunity. Viruses which can evade the host’s immune system to establish a chronic, persistent infection have a selective advantage over those viruses which are not able to evade the immune system. . Three examples of viral immune evasion strategies are described below. For each of the three strategies, please state whether virally-infected cells would be killed by i) CTLs and/or ii) NK cells, and explain why target cell killing would or would not occur (1 sentence) A) HIV taken from HLA-A2 positive individuals often harbors mutations in the sole viral epitope presented by HLA-A2, resulting in loss of binding to HLA-A2. i) HLA-A2-restricted CTLs - ii) NK cells - B) Human cytomegalovirus (HCMV) encodes a protein called US3 that binds to MHC Class I molecules and retains them in the ER, so that they never get presented on the cell surface. i) CTLs - ii) NK cells - C) Poxviruses encode a protein called crmA, which can inhibit caspases, which are proteins in the apoptosis cascade downstream of granzymes and Fas. i) CTLs - ii) NK cells- D) Other viruses have strategies to evade MHC Class II presentation, and therefore CD4+ T cell activation. Given that eradication of the infected cell requires MHC Class I presentation, give two reasons why would it be advantageous for these viruses to inhibit CD4+ T cell activation.Name: Question 5 Your very tricky colleague Dr. Dark Sircus, has used gene targeting to convert, exclusively in CD8+T cells, a QACRG motif in a cytosolic protein X to a QALRG sequence (strain A). Using the same strategy he has inactivated a protein Y also in CD8+ T cells alone (strain B). Mice A and B were crossed and homozygosed to