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Flashcards in Transplantation Deck (17):

What is an allograft?

between different members of the same species


What is an autograft?

from one part of the body to another eg skin


What is an isograft?

between genetically identical individuals eg monozygotic twins


What is a xenograft?

between members of different species eg porcine valves


Which immune cell is responsible for the rejection response?

  • T-cells recognize MHC antigen, the HLA molecules that are on the surface of most cells
  • MHC antigens that stimulate strong rejection responses are encoded by MHC genes
    • if you are twins, you have the same MHC and low-risk of rejection
    • if you are not, you have different (non-self) MHC that will be recognized as an antigen by the T cells


What is MHC Class I?

  • HLA-A, B, and C loci
  • expressed on all cells
  • present cytoplasm-derived proteins (Ags)
    • presents Ag to CD8+ T-cells


What is MHC Class II?

  • DR, DP, and DQ loci
  • presented mainly on APC and other inducible cells
  • present extracellular derived proteins (Ag) to CD4+ T cells


What is the major transplant antigen?

non-self MHC molecules


What is hyperacute rejection?

  • humoral rejection, antibody-mediated rejection
  • minutes-hours
  • caused by pre-formed anti-donor antibodies and complement to:
    • blood group
    • non-self MHC
      • can be developed through previous exposure (transfusions, pregnancy, transplant)
      • can have without this exposure as well


What is acute cellular allograft rejection?

  • occurs over days-weeks
  • caused by primary activation of T cells
    • as self-APCs travel through the graft they pick up chunks of non-self MHC
    • self-APC and non-self-APC present to T-cells in draining lymph nodes
    • activates and proliferates T-cells against non-self MHC


What is chronic allograft rejection?

  • occurs over months-years
  • not fully understood; wear and tear of not coping with many insults over time
  • slow process where function declines
  • can be caused by/a combination of:
    • episodes of acute rejection early on - T-cells in graft from day 1
    • association with viral infections - CMV
    • ischaemia-reperfusion injury (between bodies)
    • hyperlipidaemia
    • hypertension
    • infection
  • characterized by scarring or fibrosis of organs predominantly around tubules


How is allograft rejection prevented?

  • matching blood type ABO antigens
  • matching MHC alleles
  • immunosuppressive drugs


Immunosuppressive drugs target



How is graft rejection inhibited?

  • immunosuppressive drugs:
    • azathioprine - not sufficient on its own, first developed drug
    • prednisolone (steroid) - needed high doses, dangerous
    • cyclosporin - targets recently-activated T-cells


What are the commonly used immunosuppressive drugs?

cocktail of:

  • calcineurin inhibitors
    • cyclosporin, tacrolimus
  • anti-inflammatories
    • steroids
  • anti-proliferatives
    • azathioprine


How do calcineurin inhibitors work?

  • eg cyclosporin, tacrolimus
  • inhibit IL-2 gene transcription
    • IL-2 normally functions in a positive feedback loop from activated T-cells onto themselves to proliferate and activate more T-cells


What are the downsides of calcineurin inhibitors?

  • leave pt susceptible to viral infection: CMV, HSV
  • major side effect of cyclosporin is nephrotoxicity