Transplant rejection occurs when the immune system attacks foreign tissue from a transplant. There are different types of transplants based on how genetically similar the donor and recipient are. Allogeneic transplants between unrelated individuals are most likely to be rejected, while autologous and syngeneic transplants between identical twins have the lowest risk. The likelihood of rejection depends on genetic differences in proteins like MHC that allow immune cells to recognize foreign tissue. Immunosuppression drugs are used lifelong to prevent rejection by suppressing immune responses.

2. Types of Grafts • Autologous (self) e.g., BM, peripheral blood stem cells, skin, bone • Syngeneic (identical twin) • Allogeneic (another human except identical twin) • Xenogeneic (one species to another)

3. Figure 18.11

6. Transplant immunity “ Laws” of transplantation: Autogeneic grafts survive Syngeneic grafts survive Allogeneic grafts are rejected Parent-to-F1 grafts survive F1-to-parent grafts are rejected Xenogeneic grafts are rejected In an allogeneic graft, donor and recipient cells should have very similar types of surface antigens. So, why are allogeneic grafts always rejected?

8. Clinical Transplantation

9. These are averages. How well the donor and recipient are matched for MHC and minors has a big impact on graft survival. Tissue graft survival Most transplants require lifelong immunosupression with cyclosporin A or FK506. These drugs have many affects on the immune system but, overall, are not too toxic.

11. In addition to the MHC differences that usually distinguish one person from another, there are also many other genetic differences, Like MHC differences, these minor differences are manifest in proteins that can be recognized by the immune system and can be the targets of immune responses and graft rejection. Minor histocompatibility antigens can also cause graft rejection T cells usually mediate graft rejection

12. Minor histocompatibility antigens cause graft rejection after several weeks (3-8 weeks) Even a perfect MHC match between donor and recipient will result in graft rejection if there are minor-antigen differences

13. MHC a skin onto MHC a receipient  accept MHC a skin onto MHC b receipient  rejection MHC b skin onto MHC a receipient  rejection MHC b skin onto (MHC a XMHC b )F 1 receipient  accept (MHC a XMHC b )F 1 skin onto MHC b receipient  reject (MHC a XMHC b )F 1 skin onto (MHC a XMHC c )F 1 receipient  reject Any MHC the host “sees” as foreign will cause rejection Examples

14. Mechanisms of graft rejection

15. Preexisting antibodies against antigens in the graft (usually blood type antigen) can cause rapid graft rejection Hyperacute graft rejection mediated by antibodies

16. A fetus is an allograft that may induce an immune response in the mother but is usually protected from the mother’s immune system.

19. Tempo of rejection reactions

21. Hyperacute reaction due to preformed antibodies

22. Hyperacute rejection Within minutes of transplantation Results from recipient’s pre-existing, circulating Ab Ab binds donor Ag in transplanted tissue blood vessels Clotting and complement mechanisms activated Death of transplanted tissue due to lack of oxygen

33. Tissue typing

34. Identification of HLA expressed by donor and recipient

36. Cross-matching

39. The Four Classes of Immunosuppressive Drugs Table 18.4