Transplant Rejection and Immunosuppressants Flashcards
what kind of HSN (so what is causing) causes hyperacute transplant rejection; timeframe?
Type II (antibody mediated!!)--> preformed anti-donor Abs attack graft vessels = ischemia and necrosis * w/in minutes
what type of HSN causes Acute transplant rejection; timeframe
Type IV–> cytotoxic T cells react against foreign MHC I
*occurs weeks later, usually within 3 mo
Cause of chronic transplant rejection; timeframe
Months to years–> MHC I on donor tissues is perceived by host CTL as being a self- MHC I presenting foreign antigen when it isnt = obliterative vascular fibrosis and fibrosis of graft tissue
what two things mediate chronic transplant rejection
Abs AND T-cell
what type of transplant rejection is irreversible? reversible?
- Chronic is irreversible
2. Acute is irreversible with immunosuppresants
What causes graft vs host dz
Grafted T cells proliferate in the host and start reacting against all tissues (since it recognizes everything in host as foreign) –> severe organ dysfunction
T-cells causing, so is a Type IV hsn rxn
what two transplant can lead to GVH dz
- Bone marrow transplant
- Liver transplant
*both organs rich in lymphocytes
4 symptoms of GVH
- maculopapular rash (neck, shoulders, ears, palms)
- Hepatosplenomegaly
- hemolysis/ jaundice
- G.I. sx (N/V abdominal pain, diarrhea)
binds to cyclophilin and inhibits calcineurin
Cyclosporine
AE of cyclosporine
- nephrotoxicity –> due to vasoconstriction of afferent and efferent arterioles in kidney; this also leads to HTN
binds to FK-binding protein to inhibit calcineurin
Tacrolimus (FK-506)
AE of tacrolimus
like cyclosporine, can cause nephrotoxicity and HTN
what other two AEs do tacrolimus and cyclosporine share
- gingival hyperplasia
2. hirsutism
function of calcinuerin, why is blocking it helpful
transcription factor for IL-2–> no IL-2 = impaired T-cell proliferation and differentiation
binds FKBP-12 and inhibits mTOR
Sirolimus (rapamycin)
