MHC and graft rejection

MHC and graft rejection - ‫بسم اللة الرحمن‬

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Unformatted text preview: ‫بسم اللة الرحمن‬ ‫الرحيم‬ Major Histocompatibility Complex (MHC) (MHC) Major Histocompatibility Complex (MHC) Major * The MHC is a closely linked complex of genes that govern production of the major histocompatibility * In humans, MHC resides on the short arm of chromosome 6 * Three genes (HLA­A, HLA­B, HLA­C) code for the class I MHC proteins * Several HLA­D loci determine the class II MHC proteins i.e. DP, DQ and DR * HLA genes are very diverse (polymorphic) i.e. there are many alleles of the class I and II genes Major Histocompatibility Complex (MHC) Major * Between the class I and class II gene loci, there is a third locus (Class III) * This locus contains genes encoding tumor necrosis factor, lymphotoxin and two complement components (C2 and C4) * Class III antigens do not participate in MHC restriction or graft rejection MHC Class I Antigens MHC * Class I MHC antigens are : HLA­A, HLA­B and HLA­C * These antigens are glycoproteins found on surfaces of all nucleotide human cells and on platelets * HLA­A contains 24 different antigenic specificities, HLA­B contains 52 and HLA­C contains 11 * Class I MHC antigens are involved of MHC restriction of cell mediated cytotoxicity MHC Restriction MHC * Endogenously processed cytosolic peptides in virus infected cells or tumor cells are transported to the surface of the cells * They bind to MHC I molecules to be recognized by cytotoxic T­cells which then kill these cells * In other words; T­cells are only activated when they recognize both antigen and class I MHC molecules in association MHC Class II Antigens MHC Class II antigens are: HLA­DP, HLA­DQ, HLA­DR antigens These antigens are glycoproteins found on the surface of macrophages, B­cells, Dentritic cells, langerhans cells of skin and activated T cells HLA­DP contain 6 different antigenic specificities, HLA­DQ contains 9 and HLA­DR contains 20 MHC Class II Antigens MHC * Helper T­cells recognize antigens on antigen­ presenting cells only when the antigens are presented on the surface of cells in association with class II MHC * Class II antigens react with the CD4 molecule on the helper T­cells which secrete cytokines Class I MHC and Class II MHC Class MHC Class I MHC Class I MHC Class II Nomenclature HLA­A, HLA­B, HLA­C HLA­DP, HLA­DQ, Found on All nucleated somatic cells Recognized by CD8 TC cells Functions Presentation of Ag to TC cells leading to elimination of tumor or infected host cell HLA­DR Macrophages, B­cells, Dentritic cells, langerhans cells of skin and activated T cells CD4 TH cells Presentation of Ag to TH cells which secrete cytokines Transplantation Transplantation and Graft Rejection Types of grafts Types 1) Autografts : The transfer of an individual’s own tissues from place to place e.g. Skin grafts (regularly accepted) 2) Isografts : Transfer of tissues between genetically identical persons e.g. Identical twins ( accepted permanently) Types of grafts Types 3) Allografts (homograft): ­ Transfer of a graft between genetically different members of same species e.g from one human to another ­ Rejection occur if donor and recipient are not matched 4) Xenograft (heterograft): ­ Transfer of tissues between different species ­ Always rejected Mechanism Of Graft Rejection Mechanism 1) Both TH and TC are activated ­ TC cells destroy graft cells by direct contact TH cells secrete cytokines that attract and activate macrophages, NK cells and polymorphs leading to cellular infiltration and destruction of graft (Type IV) ­ B cells recognize foreign antigens on the graft and produce antibodies which bind to graft cells and . Activate complement causing cell lysis . Enhance phagocytosis, i.e. opsonization (Type II) . Lead to ADCC by macrophages, NK,PML ­ Immune complex deposition on the vessel walls induce platelets aggregation and microthrombi leading to ischemia and necrosis of graft (Type II) Types Of Graft Rejection Types !) Hyperacute rejection: ­ It occurs hours after transplantation ­ In individual with preformed antibodies either due to ­ blood groups incompatibility or previous sensitization by blood transfusion, previous transplantation 2) Acute Rejection: ­ It occurs 10 to 30 days after transplantation ­ It is mainly T­cell mediated 3) Chronic or late rejection: ­ It occurs over a period of months or years ­ It may be cell mediated, antibody mediated or both Graft Versus Host (GVH) Reaction Graft * An immunologically competent graft is transplanted into an immunologically suppressed recipient (host) * The grafted cells survive and react against the host cells i.e instead of reaction of host against the graft, the reverse occurs * GVH reaction is characterized by fever, pancytopenia, weight loss, rash , diarrhea, hepatsplenomegaly and death Thanks Thanks ...
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This note was uploaded on 12/21/2011 for the course STEP 1 taught by Professor Dr.aslam during the Fall '11 term at Montgomery College.

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