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Flashcards in Transplants and Immunoactive drugs Deck (22):

hyperacute transplant rejection

occurs within minutes when recipient has pre-existing antibodies to donor tissue. type II rxn that activates compliment. leads to widespread thrombosis of graft vessels that causes ischemia and necrosis. graft must be removed.


acute transplant rejection

occurs weeks to months of transplant.
recipient develops immunity to donor tissue. may be cell mediated or humoral. cell mediated would be due to cytotoxic T cells activated against donor MHCs. causes vasculitis of graft vessels with dense interstitial lymphocytic infiltrate.
We can suppress/prevent this with immunosuppressants.


chronic transplant rejection: mechanism

complicated. irreversible.
basically, recipient T cells start to recognize donor MHC complexes as if they were their own. However, donor tissue makes different proteins, so the recipient T cells interpret this as viral infection (recipient T cells start to recognize donor antigens). Recipient T cells attack donor tissue. there are both cellular and humoral components.


What do we see in the heart with chronic transplant rejection? What about the lungs?

heart: atherosclerosis
lungs: bchonchiolitis obliterans (destruction of the bronchioles)


What is seen in chronic transplant rejection of the liver? Of the kidneys?

liver: vanishing bile ducts
kidney: vascular fibrosis, glomerulopathy


What is graft vs. host disease?

grafted immunocompetent T cells proliferate in the immunocompromised host and start destroying recipient tissue. can cause severe organ dysfunction and may manifest as maculopapular rash, jaundice, diarrhea, or hepatosplenomegaly. Or, can be good in bone marrow transplant for leukemia (graft-vs,tumor effect)


What is the MoA of cyclosporine?

calcineurin inhibitor that binds cyclophilin. cyclosporin blocks T cell activation by preventing IL-2 transcription


What is the use and toxicities of cyclosporine?

used in transplant rejection, psoriasis, and RA
Main toxicity is NEPHROTOXICITY
(can also cause HTN, hyperlipidemia, hyperglcemia, tremor, gingeval hyperplasia, hirusitism)


What is tacrolimus?

calcineurin inhibitor that binds FKBP. this also blocks T cell activation by prevening IL-2 transcription


What is the use and toxicity of tacrolimus?

NEPHROTOXICITY. Incr. risk of DM and neurotoxicity compared to cyclosporine (less gingival hyperplasia or hirsutism).
used for transplant rejection prophylaxis.


What is the sirolimus/rapamycin?

mTOR inhibitor that binds FKBP.
this blocks T cell activation and B cell differentiation by preventing IL-2 signal transduction.


What are the uses toxicities of sirolimus?

used for kidney transplant rejection prophylaxis and drug eluting stents
it is non-nephrotoxic
(may cause anemia, thrombocytopenia, leukopenia, insulin resistance, hyperlipidemia)


What is azathioprine?

antimetabolite precursor of 6-mercaptopurine. inhibits lymphocyte prolif by blocking nucleotide synthesis.


Uses and toxicities of azathiopurine?

used for transplant rejection, RA, Crohn, glomerulonephritis, others
toxicity increased by allopurinols. they include the 'penias:' leukopenia, anemai, thrombocytopenia


What is Basiliximab?

monoclonal ab agains IL-2 receptor. used for kidney transplant rejection prophylaxis. may see edema, HTN.


How do glucocorticoids work?

inhibit NF-kB. suppress B and T cell function by decreasing the transcription of many cytokines.


Target and use of bevacizumab?

anti-VEGF used for colorectal and renal cell carcinoma


Target and use of cetuximab?

target: EGFR. for stage IV colorectal CA, head and neck CA


Target and use of rituximab?

CD20. for B cell non-hodgkin lymphoma, RA ( with methotrexate), ITP


target and use of trastuzumab?

HER2/neu. used for breast CA, gastric cancer


Target and use if infliximab

used for IBD, RA, ankylosing spondylitis, psoriasis (PAIR)


Target and use of abciximab

target: glcyoprotein IIB/IIIa. used as an anti-platelet agent for prevention of ischemic complications in pts undergoing percutaneous coronary intervention.

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