Flashcards in Organ Transplant Deck (25):
What organs can be transplanted?
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?
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
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
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?
1. Calcineurin inhibitor (tacrolimus or cyclosporine)
3. 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.
What is used as an induction agent to decrease the risk of acute rejection?
specific Ab against T and B cells.
antithymocyte globulin and OKT3- they specifically bind to T cells and tag them for destruction.
these are also used once a rejection occurs, and they are very very successful.
When is liver transplant indicated?
life-threatening or debilitating liver failure
early stage hepatocellular ca that is not resectable dt tumor location or underlying liver dz
How are livers allocated?
MELD formula- uses pt's creatinine, INR of PTT, and bilirubin.
Yields a number that directly correlates to mortality.
Livers given to pts with highest mortality (waiting time doesn't matter)
Extra points for certain early stg tumors
Liver transplant operation
need adequate blood, platelets, FFP; correct ABO type, IV abx, central monitoring
wide bilateral subcostal incision w midline extension
Dissect suprahepatic VC, isolate portal vein in porta hepatis, free liver from diaphragm above bare area.
T/F liver can be removed with the IVC
True. Can also be removed without it.
When is kidney transplant indicated?
end-stage renal dz in otherwise healthy pts
How are kidneys allocated?
formula incorporates kidney's degree of match, waiting time, if person has donated, recipient's age, recipient's degree of sensitization
T/F transplantation is superior to dialysis for quality of life but not for survival in elderly pts
Superior to dialysis in both QoL and survival, even in old ppl
Kidney txplant operation
Expose anterior rectus sheath and external oblique and go into retroperitoneal space.
Preserve spermatic cord
Dissect retroperitoneal space and allow renal vessels to be anastomosed to external iliac artery and vein
Anastamosis of ureter directly to the bladder