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MHC and transplantation

MHC & T ransplantation. MHC and transplantation. 周炫辰 邹知耕 张顺 郑艳 宗瑶 赵静. What is transplantation.

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MHC and transplantation

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  1. MHC & Transplantation MHCandtransplantation 周炫辰 邹知耕 张顺 郑艳 宗瑶 赵静

  2. What is transplantation • TransplantationIn clinical practice,organ that has functional deficiency can be replaced by a normal organ from another person to make good a functional deficit,this therapy is called transplantation.

  3. 1909 - The first kidney transplant experiments were performed in humans in France using animal kidneys. • A surgeon inserted slices of rabbit kidney into a child suffering from kidney failure.  Although “the immediate results were excellent” the child died about 2 weeks later.

  4. 1954 - Joeseph E. Murray and his colleagues at Peter Bent Brigham Hospital in Boston performed the first truly successful kidney transplant between a pair of identical twins.  This was done without any immunosuppressive medication.  • More kidney transplants between identical twins were successfully performed, and some of those kidney recipients are still alive today

  5. Graft Donor Recipient

  6. Classification of transplantation (according to source of graft) • autograft: the same individual • isograft: genetically identical individuals, i.e., identical twins • allograft: the same species • xenograft: different species

  7. The greatest problem the transplantation is faced with is the rejection that ensues After research,scientists have discovered that MHC play an important role in the rejection. If the MHC is not identical between donor and recipient,it will cause immune rejection, leading to the death of the graft.

  8. MHC——Major histocompatibility complex A large cluster of linked genes that encodes two sets of highly polymorphic cell-surface proteins,termed as: class I MHC molecules→CD8+T cells class II MHC molecules→CD4+T cells

  9. MHC is also called HLA complex in human , but H-2 complex in the mouse.

  10. Functions of MHC molecules Present antigen to T cells and initiate immune respose. T cell is activated only when MHC molecules bind to antigenic peptides.

  11. The structure of different MHC molecules are almostidentical. • The part of MHC molecule that is important in T cell recognition is the outer surface of the a helices which is highly conserved. • The significant differences between two MHC molecules lie deep in the peptide-binding groove between the a helices ,governing which peptide can bind.

  12. Molecular basis for interaction of MHC molecules and antigenic peptide

  13. Mechanism of rejection Graft and host MHC molecules present different peptides so that an immune response is triggerred.

  14. Normal situation: MHC Peptide Transplantation: MHC Peptide T cell activation MHC Peptide 1.Direct recognition of alloantigens Rejection

  15. 1.Direct recognition of alloantigens The passenger leukocytes in the graft ,that is the DCs and macrophages ,also play an important role. • Quickly • Strongly

  16. 2. Indirect recognition of alloantigens Allotype MHC molecules can be as foreign protein processed by APC and recognized by T cell of recipient. The recipient T cells recognize the peptide that is processed by recipient APC and is from donor MHC molecules. • Slowly • Weakly

  17. Mj MHC II of self-APC CD4+ T cell NK MHC II of graft-APC B cell (IL-2,IFNg) MHC I of self-APC CD8+ T cell CTL MHC I of graft-cell Role of CD4+ T cells and CD8+ T cells

  18. Graft-versus-host reaction GVHR • A special situation occurs in bone-marrow transplantation ,in which GVHR is induced by immunologically competent T cells being transplantation into allogeneic recipients which are able to reject them.

  19. Ways to prevent rejection • Tissue typing (not completely) • Immunosuppression (non-specific) • Immunological tolerance (not practical)

  20. Tissue typing by themixed lymphocyte reaction (MLR)

  21. agent mode of action application(s) organ transplant, hypersensitivity, autoimmunity organ transplant, corticosteroids, prednisone cyclosporine, ticrolimus anti-inflammatory, altering T-cell and PMN traffic inhibition of IL-2 production by T cells Inhibition of T cell activation by IL-2 organ transplant rapamycin Immunosuppressive agents

  22. agent mode of action application(s) purine metabolism organ transplant azathioprine, 6-MP organ transplant methotrexate folate metabolism autoimmune diseases, organ transplant cyclophosphamide, melphalan alkylation of DNA, RNA and proteins x-irradiation Lymphopenia malignancy/marrow transplantation Immunosuppressive agents Immunosuppressive agents

  23. Alternative ways • Stem cell • Xenograft

  24. Thank you ! The end

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