TRANSPLANTATION

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TRANSPLANTATIONtissue rejection
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• Organ transplantation
• Is the moving of an organ from one body to
  another for the purpose of replacing the
  recipient's damaged or failing organ with a
  working one from the donor site. Organ donors can
  be living or deceased
• Organs that can be transplanted
• the heart, kidneys, liver, lungs, pancreas, eyes
  and intestine.
• Tissues that can be transplanted
• bones, tendons, cornea, heart valves, veins, and
  skin

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• Types of transplants
• 1.Autograft
• Transplant of tissue to the same person.
• e.g. skin, vein, stem cells
• 2.Allograft
• Transplant of an organ or tissue between two
  genetically non-identical members of the same
  species
• Most human tissue and organ transplants are
  allografts
• 3.Isograft (Syngeneic)
• A subset of allografts from a donor to a
  genetically identical recipient (e.g. identical
  twin).
• Isografts don't trigger an immune response.
• 4.Xenograft
• A transplant of organs or tissue from one species
  to another
• e.g. porcine heart valve transplants

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• Immunologic Basis of Allograft Rejection
• Grafts rejection
• Is a kind of specific immune response to the
  organ which causes failure of the transplant
• Specificity
• Immune memory
• Transplantation antigens
• Major histocompatibility antigens (MHC
  molecules)
• Minor histocompatibility antigens
• Other alloantigens

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• Major histocompatibility antigens (MHC
  molecules)
• Main antigens of grafts rejection
• Cause fast and strong rejection
• Difference of HLA types is the main cause of
  human grafts rejection
• Minor histocompatibility antigens
• Also cause grafts rejection, but slow and weak
• Other alloantigens
• ABO blood group antigens
• Some tissue specific antigens
• Skin, kidney, heart, pancreas ,liver
• VEC (vascular endothelial cell) antigens

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• Mechanism of allograft rejection
• Cell-mediated Immunity
• Humoral Immunity
• Role of NK cells
• Cell-mediated Immunity
• T cell-mediated cellular immune response against
  alloantigens on grafts
• T cells of the recipient recognize the allogeneic
  MHC molecules
• i.e. uptake and presentation of allogeneic
  donor MHC molecules by recipient APCs
• activated CD4T cells ? MF activation and
  recruitment
• Activated CD8T cells ? Kill the graft cells

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• Humoral immunity
• Important role in hyperacute rejection
• Complements activation
• ADCC
• Opsonization
• Role of NK cells
• mediators secreted by activated Th cells can
  promote NK activation

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Classification of Allograft Rejection

• Host versus graft reaction (HVGR)
• Conventional organ transplantation
• Graft versus host reaction (GVHR)
• Bone marrow transplantation

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• Host versus graft reaction (HVGR)
• Hyperacute rejection
• Acute rejection
• Chronic rejection

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• Hyperacute rejection
• Occurs within minutes to hours after host blood
  vessels are anastomosed to graft vessels
• Pathology
• Thrombotic occlusion of the graft vasculature
• Ischemia, denaturation, necrosis
• Mechanisms
• Antibody against ABO blood type antigen
• Antibody against VEC antigen
• Antibody against HLA antigen
• Complement activation?Endothelial cell damage
• Platelets activation ? Thrombosis, vascular
  occlusion, ischemic damage

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• Acute rejection
• Occurs within days to 2 weeks after
  transplantation, 80-90 of cases occur within 1
  month
• Pathology
• Acute humoral rejection
• Acute vasculitis manifested mainly by endothelial
  cell damage
• Acute cellular rejection
• Parenchymal cell necrosis along with
  infiltration of lymphocytes and MF
• Mechanisms
• Vasculitis IgG antibodies against alloantigens
  on endothelial cell
• Parenchymal cell damage
• Delayed hypersensitivity mediated by CD4Th1
• Killing of graft cells by CD8Tc

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• Chronic rejection
• Develops months or years after acute rejection
  reactions have subsided
• Pathology
• Fibrosis and vascular abnormalities with loss of
  graft function
• Mechanisms
• Not clear
• Extension and results of cell necrosis in acute
  rejection
• Chronic inflammation mediated by CD4T cell/MF
• Organ degeneration induced by non immune factors

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Graft versus host reaction (GVHR)

• Graft versus host reaction (GVHR)
• Allogeneic bone marrow transplantation.
• Rejection to host alloantigens.
• Mediated by immune competent cells in bone
  marrow.
• Graft versus host disease (GVHD)
• A disease caused by GVHR, which can damage the
  host.
• Acute GVHD
• Chronic GVHD
• Conditions
• Enough immune competent cells in grafts.
• Immunocompromised host.
• Histocompatability differences between host and
  graft.

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• 1. Acute GVHD
• Endothelial cell death in the skin, liver, and
  gastrointestinal tract
• Rash, jaundice, diarrhea, gastrointestinal
  hemorrhage
• Mediated by mature T cells in the grafts
• 2. Chronic GVHD
• Fibrosis and atrophy of one or more of the organs
• Eventually complete dysfunction of the affected
  organ
• Both acute and chronic GVHD are commonly treated
  with intense immunosuppresion

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Prevention and Therapy of Allograft Rejection

• Tissue Typing
• ABO and Rh blood typing
• HLA typing (HLA-A and HLA-BHLA-DR)
• Screening of the recipient for anti-HLA
  antibodies (also called antibody screening)
• Lymphocyte cross matching (also called
  compatibility testing)
• Immunosuppressive Therapy
• Corticosteroids block the synthesis and
  secretion of cytokines
• Azathioprine, Cyclophosphamide block the
  proliferation of lymphocytes.