LMP299Y1 Lecture Notes - Lecture 6: Allotransplantation, Autotransplantation, Endothelium

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Published on 3 Jun 2013
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2/13/2013 8:07:00 AM
T regulatory cells clinical transplantation
Autograft self isograft genetically identical individual
Allograft different members of the same species
Shortage of graft donors waiting list patients die
Living donors: liver (regenerates fast), kidney
Increase the utility harvest lung from dead donor, damaged in process
Increase the utility of available organs
Criteria for organ donation
Brain death organ function virus infection no malignancy immunosuppression
and cancer
Resect cancer then transplant?
Minor histocompatibility eg male to female, female can recognize
Others: blood group antigens, Tissue sp
Donor APC is direct
Recipient APC
Cd4
Acute vascular rejection or acute cellular rejection
most often in clinic
cells of the graft blood vessel
mediated by abs to alloantigens on endothelial cells
direct lysis of endothelial
necrosis of parenchymal cells
t cell mediated cytotoxicity
immunosuppress chronic graft failure antibody and t cell mediated
fibrosis
irreversible
kidney allograft artery blocked near obliteration of the vessel lumen
reduce immunogenicity ABO HLA matching
suppress the immune response recipients w drugs
induce tolerance in recipients
corticosteroids side effects hyperlipidemia diabetes
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rapamycin
cyclosporine A side effects nephrotoxicity
disadvantages toxicity infection malignancy still can’t prevent chronic
rejection
Goals:
immune competent host
no maintenance immunosuppression: costs, side effects
prevention of acute rejection
moving towards tolerance
unresponsiveness to graft but not other antigens
complication free aceeptance of graft
specifically to donor antigens
central and peripheral tolerance
wipe out bone marrow then reconstitute with donor cells
recipient becomes chimera
central tolerance neonatal tolerance induction of chimeras
harsh treatment
peripheral tolerance prevent activation eliminate anti donor tcells
memory tcell depletion
block signal 1
signal 2 costimulatory blockade cd154-cd40
b cell depletion block ab production
lymphocyte trafficking to the organ
anti LFA
strategies
ctla4 Ig fusion which will bind B72
but in humans belatcept CTLA2 Ig vs cyclosporine
similar graft marginal improvement
treg
inhibit immune responses mediated by other lymphocytes
in diseases: hypersensitivity and allergy
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