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Microbiology and Immunology > Transplantation > Flashcards

Flashcards in Transplantation Deck (17):
1

What is an allograft?

between different members of the same species

2

What is an autograft?

from one part of the body to another eg skin

3

What is an isograft?

between genetically identical individuals eg monozygotic twins

4

What is a xenograft?

between members of different species eg porcine valves

5

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

6

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

7

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

8

What is the major transplant antigen?

non-self MHC molecules

9

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

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10

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

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11

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

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12

How is allograft rejection prevented?

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

13

Immunosuppressive drugs target

T-cells

14

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

15

What are the commonly used immunosuppressive drugs?

cocktail of:

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

16

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

17

What are the downsides of calcineurin inhibitors?

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