Mechanisms of transplant rejection Flashcards
What two things do you try and match in said organs transplants?
blood group and HLA.
What other things might be better matched regarding chronic rejection?
minor histocompatibility antigens.
What assay is done to test for allorecognition?
mixed lymphocyte reaction
Direct allorecognition and indirect allorecognition?
direct: donor DCs travel to host LN and alloreactive T cells recognise mismatched HLA and become activated. Can go and cause damage in the graft.
Indirect: host APCs will pick up host peptides (could be from mismatched HLA) and present it to T cells. Unlikely T cells can do direct damage but they can stimulate macrophages and antibodies.
What happens in hyperacute rejection?
Ab against donor-derived antigens, normally ABO antigens (or HLA?), causes complement activation and coagulation- vessel occlusion.
What things can increase the chances of having antibodies against donor antigens for hyperacute rejection?
xenograftss, pregnancy, transplants, transfusions.
How might NK cells help in rejection?
MIC upregulated in stressed graft and the NK cells with NKGD can attack.
Azathioprine name and effect?
6-mercaptopurine will inhibit purine metabolism nd stop cell cycle.
What does mycophenolate do?
inhibits purine synthesis and cell cycle via monophosphate dehydrogenase inhibition.
Especially in salvage pathway in lymphocytes.
What are CD154 and CD152
CD154 is CD40L and
CD152 is CTLA-4
Normal course of induction therapy for transplants?
depleting biologic alongside some of the other immunosuppressive drugs.
not using sirolimus because of ineffecitve healing with it.
What for maintenance therapy?
Immunosuppressive drugs, but not biologics.
how does sirolimus work?
binds FKBP and inhitbis mTOR.
How do tacrolimus and cyclosporine work?
cyclosporin binds cyclophilin and tacrolimus bind FKBP12 which inhibits calcineurin activation of NFAT.
Which immunosuppressives have renal toxicity?
sirolimus and calcineurin inhibitors.
