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Transplant

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Topic updated on 02/09/13 6:46pm

Graft types
  • Autograft
    • moved from one location to another in self
    • only type that does not require immunosuppresants to prevent rejection
      • e.g. skin graft, vessel graft
  • Isograft/Syngenic graft
    • from genetically identical source
    • although same genotype, different MHC recombinations
      • e.g. monozygotic twin
  • Allograft
    • from nonidentical/genetically different individual of the same species
      • e.g. blood transfusion from blood bank
  • Xenograft
    • from different species
      • e.g. porcine heart valve  
Rejection
  • Effector mechanisms
    • CTLs, macrophages, CD4 lymphocytes
      • secrete inflammatory cytokines
    • antibodies
  • Types of rejection
    • hyperacute
      • antibody mediated due to the presence of preformed antidonor antibodies in the transplant recipient
        • type II hypersensitivity
      • occurs within minutes after transplantation
      • results in complement activation >> endothelial damage >> inflammation >> thrombosis
    • acute
      • cell mediated due to cytotoxic T lymphocytes reacting against foreign MHCs
      • occurs weeks after transplantation
      • results in parenchymal cell damage or endothelialitis >> inflammation
    • chronic
      • T cell- and antibody-mediated vascular damage
        • obliterative vascular fibrosis >> intimal smooth muscle proliferation >> vessel occlusion >> organ atrophy
      • occurs months to years after transplantation
      • irreversible
      • class I-MHCnon-self is perceived by CTLs as class I-MHCself presenting a non-self antigen
  • Graft-versus-host disease
    • grafted immunocompetent T cells proliferate in the irradiated immunocompromised host
      • reject host cells with "foreign" proteins
    • results in severe organ dysfunction
      • maculopapular rash, jaundice, hepatosplenomegaly, and diarrhea
    • necessary to remove mature T cells before implantation
Tissue compatibility testing
  • Must match
    • ABO blood group
      • expressed by RBCs as well as endothelial cells
    • HLA type
      • focused on
        • HLA-A
        • HLA-B
        • HLA-DR
  • Tests
    • class I
      • microcytotoxicity test
        • donor cells added to antisera containing specific antibodies against a certain HLA type
        • if cells contain that antibody type antibodies will bind
        • cell becomes leaky and takes up a dye
        • cells without antibody will not take up the dye
        • same process done for the host
    • class II
      • mixed lymphocyte reaction
        • donor cells irradiated to prevent division
        • host blood added
        • if T-cells respond to antigens on donor cells they will proliferate
        • radio active thymidine in the test mixture taken up and can be measured
          • if no thymidine is taken up, there is no rejection
Prevention and treatment of tissue rejection
  • Immunosuppresant drugs
    • see "Immunosuppresant drugs" topic
  • Graft recipient risks infection from immunosuppresion
  • Certain tissues grafts do not require immunosuppresion
    • e.g. the eye is an immunoprivileged site
      • corneal transplant does not require


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