Biol 430 Question Bank Transplantation 1. For each of the transplants listed below: a. Indicate in the Transplant type column: “syngenic”, “allogeneic” or “xenogeneic” b. Indicate in the Response column if the graft will be “accepted” or “rejected” and if the graft will be rejected: c. Indicate in the Rejection type column: “Hyperacute” or “Acute” Donor Recipient Transplant type C57BL/6 Balb/c C57BL/6 Rat C57BL/6 C57Bl/6 C57BL/6 C57BL/6 X Balb/c hybrid Response Rejection type C57BL/6 X Balb/c Balb/c hybrid 2. Suppose that a child needs a kidney transplant but does not have an identical twin. The parents, brother and sister all are willing to donate a kidney, and testing showed that the parents’ genotypes are HLAD/F and HLAD/H. A. What do the ‘D/F’ and ‘D/H’ letters mean? Use the diagram to the right to predict the haplotypes possible among the children. B. If your haplotype is HLAF/H, what is the probability that one of your siblings will have the same HLA alleles? C. If one of your siblings is an exact HLA match, does this mean that there will be no rejection? Explain. 3. Match the type of transplant with the appropriate example. Type of transplant ___ isograft ___ allograft ___ xenograft ___ autograft Biol 430 Example A. using a pig heart valve to replace a human one B. a human heart transplant C. a skin graft between identical twins D. using a leg artery during cardiac bypass surgery Question Bank Transplantation Page 1 4. This figure shows the results of HLA-typing for HLA-DR and HLA-B for a recipient and 5 potential kidney donors. Considering the two HLA loci examined, which donor would be the best match? A. Do the recipient and donor share HLA alleles where the wells are both blue or both clear? Explain. B. Under each HLA type (HLA-DR and HLA-B), what differs between columns 1 – 5? C. Theoretically, achieving a perfect tissue match would require comparing all HLA genes for every possible type of allele, howver, this is not necessary (or practical). Explain. D. Which donor (A, B, C, D or E) would be the best match with the recipient? Explain. 5. Determine if each of the following statements is True or False, and if it is false, explain why. a. ___ Direct T-cell allorecognition can occur when graft antigens are presented by recipient DCs that activate recipient T-cells. b. ___ A xenograft will most likely trigger a cell-mediated acute rejection. c. ___ In general, when pairing organ donor and recipient, matching of MHC-II alleles is more important than matching of MHC-I. d. ___ Fortunately, rejection of a subsequently transplanted organ is likely to be weaker than the previous transplant. e. ___ An identical twin is a better source of organs than a fraternal twin. f. ___ Acute tissue rejection is a manifestation of a Type III hypersensitivity. g. ___ There is an inverse linear relationship organ survival time (years) between the number of HLA mismatches h. ___ Graft vs Host disease is a common complication of a bone marrow transplant. i. ___ Indirect T-cell allorecognition occurs when graft antigens are presented by graft DCs to recipient T-cells. Biol 430 Question Bank Transplantation Page 2 6. Graft rejection is strongest when the donor and recipient have greatest differences in HLA haplotype. A. During development in the thymus, T-cells are positively selected for TCRs that can bind to self-HLAs; thus, theoretically, T-cells of the recipient should not bind to HLA on cells of the graft. Yet, in ‘direct’ allo-recognition the recipient T-cells are activated by peptides presented on graft HLAs; explain why this happens. B. Often, perfusing a transplanted with saline to remove lymphatic cells can reduce immunological rejection. Why? C. Explain why HLA differences between the graft and recipient play the major role in graft rejection during ‘indirect’ allo-recognition, but less so during ‘direct’ allo-recognition. D. Even if the donor and recipient have the same HLA haplotype, long-term chronic rejection is likely to occur. Explain why. 7. A variety of tissues can be transplanted with a low risk of rejection. For each of the following examples explain why allograft rejection is not commonly observed. A. Heart valve replacement. B. Bone graft. C. Cornea transplants. 8. A stem cell transplant would be appropriate under which one of the following circumstances. Explain your choice. A. DiGeorges syndrome C. malignancies of non-immune cell tissues B. chronic graft rejection D. SCID. 9. Monoclonal antibodies, such as rituximab, are widely prescribed as anti-rejection therapy and for a variety of autoimmune disorders. A. What does it mean that these antibodies have been ‘humanized, and why is this important? B. How does rituximab function? C. If you could design an ideal anti-rejection drug, what properties would you design for it? Biol 430 Question Bank Transplantation Page 3 10. Several methodologies can be used to best match donor and recipient prior to transplantation. A. What is the difference between ‘allo-antibody screening’ and ‘HLA matching’? C. Which method helps to reduce hyperacute rejection? Which acute rejection? B. How is HLA match via ‘serological matching’ different from ‘DNA analysis’. Why can these methodologies not assure that all HLA are matched? 11. Suppose there were an inverse linear relationship between the number of HLA mismatches and organ survival time (years). A. In the diagram to the right, show how the line might line might appear. (Assume the lowest survival after 10 years is 40% and the highest is 80%). B. But this is not the relationship that is actually observed. Draw in with a dashed line a more accurate representation of the relationship. C. Identify at least two reasons why the relationship in non-linear? Biol 430 Question Bank Transplantation Page 4