信號(hào)旗是如何制作的？

1、 MHC and transplantationMHC &Transplantation周炫辰 鄒知耕 張順鄭艷 宗瑤 趙靜信號(hào)旗http:/What is transplantationnTransplantationIn 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.n

2、1909 - The first kidney transplant experiments were performed in humans in France using animal kidneys. oA 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. n1954 - Joeseph E. Murra

3、y 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. nMore kidney transplants between identical twins were successfully performed, and some of th

4、ose kidney recipients are still alive todayGraftDonorRecipient Classification of transplantationnautograft: the same individualnisograft: genetically identical individuals, i.e., identical twins nallograft: the same speciesnxenograft: different species(according to source of graft)The greatest probl

5、em the transplantation is faced with is the rejection that ensuesAfter 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.MHCMajor histocompati

6、bility complex A large cluster of linked genes that encodes two sets of highly polymorphic cell-surface proteins,termed as: class I MHC moleculesCD8+T cells class II MHC moleculesCD4+T cells nMHC is also called HLA complex in human , but H-2 complex in the mouse. Functions of MHC moleculesPresent an

7、tigen to T cells and initiate immune respose.T cell is activated only when MHC molecules bind to antigenic peptides.The structure of different MHC molecules are almost identical.The part of MHC molecule that is important in T cell recognition is the outer surface of the a helices which is highly con

8、served.The significant differences between two MHC molecules lie deep in the peptide-binding groove between the a helices ,governing which peptide can bind.Molecular basis for interaction of Molecular basis for interaction of MHC molecules and antigenic peptideMHC molecules and antigenic peptideMech

9、anism of rejectionMechanism of rejectionGraft and host MHC molecules present different peptides so that an immune response is triggerred.Normal situation: MHCPeptide T cell activationTransplantation: MHCMHCPeptide Peptide1.Direct recognition of alloantigensRejection1.Direct recognition of alloantige

10、nsThe passenger leukocytes in the graft ,that is the DCs and macrophages ,also play an important role.nQuicklynStrongly2. Indirect recognition of alloantigensAllotype MHC molecules can be as foreign protein processed by APC and recognized by T cell of recipient.The recipient T cells recognize the pe

11、ptide that is processed by recipient APC and is from donor MHC molecules.nSlowlynWeaklyRole of CD4+ T cells and CD8+ T cellsCTLMjMHC II of self-APCMHC II of graft-APCCD4+ T cellMHC I of self-APCCD8+ T cell(IL-2,IFNg)NKB cellMHC I of graft-cellGraft-versus-host reaction GVHRA special situation occurs

12、 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.Ways to prevent rejectionTissue typing (not completely)Immunosuppression (non-specific)Immunological tolerance (not practical)

13、Tissue typing by themixed lymphocyte reaction (MLR) Immunosuppressive agentsapplication(s)mode of actionagentcorticosteroids, prednisoneanti-inflammatory, altering T-cell and PMN trafficorgan transplant, hypersensitivity, autoimmunitycyclosporine, ticrolimusinhibition of IL-2 production by T cellsorgan transplant, rapamycinInhibition of T cell activation by IL-2organ transplant Immunosuppressive agentsImmunosuppressive agentsapplication(s)mode of actionagentazathioprine, 6-MPpurine metabolismorgan transplantmethotrexatefolate metabol