PHRD5015 Lecture 22 - Transplantation (Ju)

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  1. cell, tissue, or organ that is taken from one individual and placed into a different individual
  2. reaction caused by allograft rejection
    host T cell-mediated immune reaction
  3. graft from a donor who is of the same species but genetically non-identical to the recipient
    allogeneic graft (allograft)
  4. graft transplanted between 2 genetically identical individuals
    syngeneic graft
  5. main antigen targets in allograft rejection
    allogeneic donor MHC molecules
  6. direct recognition of allogeneic MHC
    T cell recognition of the intact allogeneic-MHC molecules displayed by donor APCs in the graft
  7. indirect recognition of allogeneic MHC
    process & presentation (by recipient APC) of donor allogeneic-MHC antigens in association with self-MHC molecules
  8. 3 ways to minimize alloantigenic differences between donor & recipient
    • 1) match ABO Ag's
    • 2) screen for Ab's against donor
    • 3) match HLA
  9. Rh(D) Ig site of action
    neutralizes the Ag (1st step) so no rxn occurs
  10. corticosteroid site of action
    inhibit production of pro-inflammatory cytokines (2nd step)
  11. immunosuppressive Ab (OKT3) site of action
    inhibit T cell activation by blocking molecules on T cells

    (anti-lymphocyte, anti-IL-2 Ab's)
  12. T-cell signaling inhbitor (cyclosporine, tacrolimus, sirolimus) site of action
    inhibit IL-2 production by T cells
  13. anti-proliferative agent (azathioprine, mycophenolate mofetil) site of action
    inhibit clonal expansion of effector T- & B-cells
  14. what cyclosporine (CsA) binds to
  15. what tacrolimus (FK506) binds to
    FK binding protein (FKBP)
  16. MOA of CsA and FK506
    complex of drug-immunophillin binds to calcineurin and blocks its fcn -> IL-2 production inhibited
  17. 4 classes of immunosuppressive drugs
    • 1) corticosteroids
    • 2) anti-proliferative agents
    • 3) T-cell signaling inhibitors
    • 4) immunosuppressive antibodies
  18. examples of anti-proliferative agents
    azathioprine, mycophenolate mofetil (Cellcept)
  19. examples of T-cell signaling inhibitors
    • calcineurin inhibitors (CsA, FK506)
    • TOR inhibitors (sirolimus (rapamycin))
  20. examples of immunosuppressive antibodies
    • anti-lymphocyte Ab's 
    • anti-cytokine Ab's
  21. drug shown to be more effective than CsA
  22. sirolimus MOA
    binds to FKBP and inhibits TOR -> inhibits GF mediated T/B-cell proliferation
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PHRD5015 Lecture 22 - Transplantation (Ju)
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