Transplantation PDF

TRANSPLANTATION Surgical procedure by which a tissue or organ is removed and replaced by a corresponding part, either from another part of the body or from another individual, i.e.moving an organ from one person (the donor) to another (the recipient)...

TRANSPLANTATION Surgical procedure by which a tissue or organ is removed and replaced by a corresponding part, either from another part of the body or from another individual, i.e.moving an organ from one person (the donor) to another (the recipient) 86 TYPES OF TRANSPLANTATION 87  Transplant rejection
A major barrier to transplantation is the process of rejection, in which the recipient’s immune system recognizes the graft as foreign and attacks it
One of the important goals of immunologic research is successful transplantation of tissues in humans without rejection
Rejection is a complex process in which both cell mediated and circulating antibodies play a role 88  T Cell-Mediated Reactions T cell-mediated graft rejection is called cellular rejection, and it is induced by two mechanisms:
destruction of graft cells by CD8+ CTLs and
delayed hypersensitivity reactions triggered by activated CD4+ helper cells The recipient’s T cells recognize antigens in the graft (the allogeneic antigens) by two pathways direct and indirect 89  Transplant rejection
Mechanisms involved in transplant rejection – T cell mediated – delayed type hypersensitivity Direct pathway via recipient CD4+ and CD8+ recognition of MHC I antigens on donor APCs Indirect pathway whereby processing of antigen by the recipient’s APCs is required – Antibody mediated – immediate hypersensitivity 90 91  It is postulated that the direct pathway is the major pathway in acute cellular rejection, whereas the indirect pathway is more important in chronic rejection. However, this separation is by no means absolute. 92  Antibody-mediated reactions This process is called humoral rejection, and it can take two forms. Hyperacute rejection occurs when preformed antidonor antibodies are present in the circulation of the recipientр e.g. after already rejected a kidney transplant In recipients not previously sensitized to transplantation antigens, exposure to the class I and class II HLA antigens of the donor may evoke antibodies 93  Immunopathology Morphology of transplant rejection
Host vs. graft reactions
Graft vs. host reactions 94  Immunopathology Transplant rejection
Host vs. graft reactions – With kidney transplants, a close match of MHC I and II antigens is sought (less important with heart and liver transplants) – Transplant rejection is treated with immunosuppressive drugs such as cyclosporine (inhibits IL-2 formation) or anti- thymocyte globulin (anti-CD3) 95  Transplant rejection Host vs. graft reactions
The engrafted organ becomes a chimera, as the recipient’s leukocytes enter the transplant
A reverse migration of immune cells also occurs, as dendritic cells from the graft enter the host These interactions are tolerogenic, and the graft may eventually be accepted with minimal immune suppression. 96  Transplant rejection Host vs. graft reactions – Hyperacute: due to preformed antibodies, usually in multiparous women - rare – Acute: mixed antibody and T-cell response, usually controlled adequately by chemotherapy Acute cellular rejection Acute humoral rejection – Chronic: rejection occurs months to years post-transplant 97  Hyperacute Rejection Host is sensitized with Ag of the donor previously Gross - cyanotic, flaccid kidney Hemorrhages due to vasculitis Cortical necrosis 98  Sequence of events
Ag-Ab reaction at the level of vascular endothelium
Thrombotic occlusion in arterioles
Fibrinoid necrosis in arteries
distal necroses (infarction) Hyperacute rejection 99  Hyperacute rejection Within minutes or hours after restoring blood circulation in the donated organ
Micro - classic Arthus reaction
Ig and complement are deposited in blood vessels wall
early EC injury and fibrin/platelet thrombi
accumulation of PMN in arterioles and glumeruli 100 Hyperacute rejection 101  Acute Rejection Gross - pale, edematous kidney Hemorrhages due to vascular damage Superimposed changes by immunosuppresive therapy 102  Acute rejection
Within days after transplantation or may appear suddenly after immunosupression termination
Both cellular (delayed type) and humoral injuries occur
Microscopically - interstitial mononuclear cell infiltrates (macrophages, plasma cells, CD4+, CD8+) - rejection vasculitis 103  Antibody-mediated acute damage The blood vessel is markedly thickened, the lumen is obstructed by proliferating fibroblasts and foamy macrophages. 104 Antibody-mediated acute damage 105 Acute cellular rejection of a renal allograft An intense mononuclear cell infiltrate occupies the space between the tubules. 106  Chronic rejection Develops months or years post-transplant Progressive dysfunction The arteries show intimal fibrosis Interstitial mononuclear infiltrates are present, containing also plasma cells and eosinophils 107 Chronic rejection in a kidney allograft 108  Graft arteriosclerosis The vascular lumen is replaced by an Chronic rejection in a accumulation of SMC and connective tissue kidney allograft in the vessel intima. 109  Immunopathology Morphology of transplant rejection
Host vs. graft reactions
Graft vs. host reactions 110  Transplant rejection Graft vs host (GVH) reactions – Occurs primarily in bone marrow transplantation, because few immune cells are contained in transplanted solid organs – Affects the skin, GI tract, liver, and lung, causing symptoms similar to the systemic autoimmune disorders (SLE, scleroderma, etc.) 111 GVH disease occurs in any situation in which immunologically competent cells or their precursors are transplanted into immunologically crippled recipients, and the transferred cells recognize alloantigens in the host The immunocompetent T cells present in the donor marrow recognize the recipient’s HLA antigens as foreign and react against them. Both CD4+ and CD8+ T cells recognize and attack host tissues 112  Acute GVH disease Occurs within days to weeks after transplantation major clinical signs result from involvement of: the immune system and epithelia of: - skin - a generalized rash leading to desquamation - Liver - small bile ducts - jaundice - Intestine mucosal ulceration - bloody diarrhea 113  Acute GVH a generalized rash leading to desquamation 114  Chronic GVH May follow the acute syndrome or may occur insidiously Extensive cutaneous injury is common, with skin appendages destruction and fibrosis of the dermis. The changes may resemble systemic sclerosis. 115  Chronic GVH Chronic liver disease manifested by cholestatic jaundice is also frequent. Damage to the gastrointestinal mucosa may cause esophageal strictures. The immune system is devastated, with involution of the thymus and depletion of lymphocytes in the lymph nodes. 116