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Days aer transplantaon role of ischemia reperfusion

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Unformatted text preview: D8+) as well as NK cells can mediate allogra; rejec#on •  Immunosuppressive therapy is required to maintain an allogra; working •  This medica#on act by different mechanisms: –  Decreasing number of blood cells (e.g. azathioprine) –  Inhibi#ng T cell ac#va#on by: •  Blocking NF- AT nuclear transloca#on (cyclosporine, tacrolimus) •  Blocking IL- 2 receptor signalling (sirolimus) •  Blocking cos#mula#on (B7 blockade) –  Blocking lymphocyte recircula#on (S1P antagonists) –  Blocking adhesion molecules –  Other mechanisms (steroids) 1 0.9655 0.9813 0.9532 0.9701 0.9178 0.9404 0.9 0.9072 0.8952 Survival Probability 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0 3 Months 1 Year 3 Years Quebec 5 Years Rest of Canada Source: J. Chin, Canadian Organ Replacement Register, 2011, CIHI 1 0.9495 0.9579 0.9264 0.9302 0.8854 0.9 0.8667 Survival Probability 0.8 0.8334 0.8014 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0 3 Months 1 Year 3 Years Quebec 5 Years Rest of Canada Source: J. Chin, Canadian Organ Replacement Register, 2011, CIHI •  Despite the increase in allogra; survival (>90% one year gra; survival), late loss of allogra;s a;er 6 months of transplant con#nues to be a problem (e.g., haf- life of kidney allogra;s ~ 8 yr) •  Why? Uncertain, likely mul#factorial (immune and non- immune): –  Ischemia- reperfusion injury caused by organ procurement: •  Cold ischemia = preserva#on of organ form extrac#on to implanta#on •  Warm ischemia = #me between implanta#on and ini#a#on of blood supply –  Accumulated vascular injury leading to hypoperfusion, ischemia, fibrosis and cell death, caused by: •  cumula#ve acute rejec#on episodes •  an#body- mediated injury (an#- class II IgG1/G3 an#bodies) •  drug toxicity –  Viral infec#ons –  Recurrence of disease –  Drug toxicity •  Tissue- dependent hLp://www.medscape.org/viewar#cle/449640 •  Due to chronic immunosuppression –  INFECTION: •  Exogenous infec#ons •  Reac#va#on of endogenous virus –  CANCER: •  Hematological malignancies •  Skin cancers •  •  •  •  38 yr old man 20 yr history of Type I Diabetes Mellitus Examina#on: end- stage renal failure Starts transplant ‘rou#ne’ •  What are the advantages/disadvantages of living vs. cadaveric kidney transplants? •  Why do transplant recipients need to take immunosuppressive drugs? •  What are the main complica#ons of organ transplanta#on? •  Mature T cells in the...
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This note was uploaded on 09/23/2013 for the course MIMM 314 taught by Professor Rogerpalfree during the Winter '11 term at McGill.

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