Organ Transplant Flashcards
What organs can be transplanted?
kidney heart liver lung pancreas small intestines
What is the MHC antigen in humans called? Where is it found?
HLA (human leukocyte antigen)
On short arm of Chr 6
How are HLA antigens classified?
Class I or Class II
Where are Class I MHC complexes located?
All nucleated cells in the body.
They are targets for cytotoxic T cells.
Where are Class II MHC complexes located?
B cells
Monocytes, macrophages
activated T cells
They’re imp in Ag presentation
What cells/components are involved in a rejection reaction with mismatched HLA antigens?
cytotoxic T cells activated helper T cells B lymphcytes activated macrophages antibodies. The reaction is cellular in nature and is T cell-dependent.
In a rejection reaction, what do Class I antigens do?
stimulate cytotoxic T cells, causing donor tsu destruction
In a rejection reaction, what do Class II antigens do?
activate helper T cells
helper T cells plus activated cytotoxic T cells make IL-1 and IL-2, which further activate macrophages and B cells (which rls Ab)
T/F Most rejections are cell-mediated
True.
But humoral rejections are also possible.
How do humoral rejections occur?
Immediately after transplant, dt pre-formed Ag against Class I Ag in the recipent.
Acquired via prev blood transfusions, pregnancies, transplants.
(this is hyperacute rejection)
How can you avoid hyperacute rejection?
crossmatch pt’s serum w donor lymphcytes to look for pre-existing Ab against donor tsu Ag’s.
What is a typical immunosuppresive regimen?
Three drugs:
- Calcineurin inhibitor (tacrolimus or cyclosporine)
- Steroids
- Antimetabolite (mycophenolate mofetil, MMF; can also use azathioprine or Cytoxan)
How do calcineurin inhibitors work?
Tacrolimus or Cyclosporine
They find to immunophilins and inhibit calcineurin activity, which is needed for the transcription of genes that activate T-cells, like IL-2, IL-3, IL-4, IFN
How do steroids work as part of an immunosuppresive regimen?
They alter the transcription and translation of genes responsible for cytokine synthesis
They inhibit T cell activation by blocking IL-1, IL-2, IL-6, IFN synthesis
THey have local anti-inflam effects
How do antimetabolites work as part of an immunosuppressive regimen?
MMF is rapidly converted to MPA (mycophenolic acid), which inhibits inosine monophosphate dehydrogenases, which blocks the proliferation of T and B lymphocytes (so Ab production is inhibited), and blocks cytotoxic T cells.
MPA also downregulates the expression of adhesion molecules on lymphocytes.
