TRANSPLANTATION - PowerPoint PPT Presentation

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TRANSPLANTATION

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... with a working one from the donor site. Organ donors can be living or ... 1.Autograft Transplant of tissue ... kidney, heart, pancreas ,liver ... – PowerPoint PPT presentation

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Title: TRANSPLANTATION


1
TRANSPLANTATIONtissue rejection
2
  • 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

3
  • 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

4
  • 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

5
  • 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

6
  • 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

7
  • 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

8
Classification of Allograft Rejection
  • Host versus graft reaction (HVGR)
  • Conventional organ transplantation
  • Graft versus host reaction (GVHR)
  • Bone marrow transplantation

9
  • Host versus graft reaction (HVGR)
  • Hyperacute rejection
  • Acute rejection
  • Chronic rejection

10
  • 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

11
  • 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

12
  • 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

13
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.

14
  • 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

15
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.
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