mhc-在遺傳和移植中的作用 課件

1、1Major Histocompatibility Complex(MHC)What is MHC?HLAH-2Minor histocompatibility antigens2Progress in organ transplantation3Significance of the MHCrole in immune responserole in predisposition to diseaseRole in organ transplantation4Genetic barriers to transplantationautologous: in the same individu

2、alisologous: between genetically Identical individuals, i.e., identical twins (inbred animals)homologous: between individuals of the same speciesheterologous: between individuals different species5The laws of transplantation6Histocompatibility antigensand graft survival7Graft versus host disease8Gra

3、ft versus host disease9The human MHC genesclass IIclass IDPDQDRBCABCADPDQDR122211931 221 310The mouse MHC genesIDKAEclass IIclass Iclass Iclass III(C4, factor-B,TNF, etc.)11Polymorphism of MHC genes12The inheritance of MHC genesJackJillDPDQDRBCA1234BoKimMoLee1341234213MHC products expressed on cells

4、 14Crossing overresults in new haplotypes15 Class-I expressed on all nucleated cells in man, and also on erythrocytes in mice. Class-II expressed primarily on antigen presenting cells (dendritic cells, macrophages and B cells)16 Class-I expressed on all nucleated cells in man, and also on erythrocyt

5、es in mice. Class-II expressed primarily on antigen presenting cells (dendritic cells, macrophages and B cells)Differential expression of MHC antigens17Serological tissue typing:the scheme18Tissue typing by themixed lymphocyte reaction (MLR)19Tissue typing:the MLR scheme20Lymphocyte proliferation du

6、ring MLR 21Cytotoxic T lymphocyte (CTL) generationCD4+TH1CD8+CTLCD8+preCTL22InflammationlysisADCClysisIL2, IFN(TNF, NO2IL2, IL4, IL5IL2, TNF, IFN(rejectionMechanisms of graft rejection23Tempo of rejection reactionchronictype of rejectionacceleratedhyperacuteacutemonths-yearstime takenminutes- hoursd

7、aysdays-weeksunclear causes: cross reactive Ab, immune complexes, slow cellular reaction, tolerance breakdown, disease recurrencecausepreformed anti-donor antibodies and complementreactivation of sensitized T cells (secondary response)primary activation of T cells24HLA matching and graft survival25B

8、lood transfusion and graft survival26Immunosuppresseive agentsagentmode of actionapplication(s)corticosteroids, prednisoneCyclosporin FK-06, rapamycinanti-inflammatory, altering T-cell and PMN trafficinhibition of IL-2 production by T cellsInhibition of T cell activation by IL-2organ transplant, hyp

9、ersensitivity, autoimmunityorgan transplantorgan transplant27agentmode of actionapplication(s)azathioprine, 6-MPmethotrexatecyclophosphamide, melphalanx-irradiationpurine metabolismfolate metabolismalkylation of DNA, RNA and proteinsLymphopeniaorgan transplantorgan transplantautoimmune diseases, org

10、an transplantmalignancy/marrow transplantationImmunosuppresseive agents28Mode of action of some immunosuppressive agents29Removal of T cells from marrow graft MagnetMagnetic antibodies30HLA and disease associationDiseaseAssociated allelesFrequency inRelative riskpatientscontrolAnkylsoing spondylitisReiters diseaseAcute anterior uveitisPsoriasis vulgarisDermatitis herpetiformisB27B27B27CW6DR3979528785999332687.437.010.413.315.431Organ transplant activ