Immunology 25 - Immunology 25- Transplant Immunology Graft...

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Graft Rejection is an immunological response mediated primarily by T cells Skin can be grafted with 100% success between different sites on the same animal or person (autograft) or between genetically identical animals or people (syngeneic graft) When skin is grafted between unrelated or allogeneic individuals (allograft), the graft initially survives but is then rejected about 10-13 days after grafting= acute rejection; depends on a T cell response in the recipient (skin grafted onto nude mice, which lack T cells, is not rejected); ability to reject skin can be restored to nude mice by the adoptive transfer of normal T cells Accelerated rejection= when a recipient that has previously rejected a graft is regrafted with skin from the same donor the second graft is rejected more rapidly; skin from a third party donor grafted onto the same recipient at the same time does not show this faster response but follows a first-set rejection course; the rapid course of second-set rejection can be transferred to normal or irradiated recipients by T cells from the initial recipient (second set rejection is caused by memory type immune response from clonally expanded and primed T cells specific for the donor skin) Immune responses are the major barrier to effective tissue transplantation, destroying grafted tissue by an adaptive immune response to its foreign proteins; mediated by CD8, CD4 or both; antibodies can also contribute to second set rejection of tissue grafts Transplant rejection is caused primarily by the strong immune response to nonself MHC molecules Alloantigens= antigens that differ between members of the same species; immune response against these antigens= alloreactive response Differ at MHC= active immune response is directed at the nonself allogeneic MHC molecules or molecules present on the graft; in most tissues they will be predominantly MHC I antigens Once a recipient has rejected a graft of a particular MHC type, any further graft with the same MHC molecules will be rapidly rejected in a second set response Frequency of T cells specific for any nonself MHC molecule is relatively high, making differences at MHC loci the most potent trigger of the rejection of initial grafts; the MHC was originally named because of its central role in graft rejection Can no give immunosuppressant’s to avoid the MHC barrier; MHC matching still remains important for bone marrow transplantation Even a perfect match at MHC locus does not prevent rejection reactions; result of differences between antigens from non MHC proteins that also vary between individuals Unless the donor and recipient are identical twins, all graft recipients must be given immunosuppressive drugs chronically to prevent rejection Accurate matching of tissue types is achieved only rarely (exception= matched sibling donation of kidneys) In MHC identical grafts, rejection is caused by peptides from other alloantigens bound to graft MHC molecules
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Immunology 25 - Immunology 25- Transplant Immunology Graft...

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