transplants Flashcards
autograft
one part of the body to another, same person
ex- skin graft
isograft
between genetically identical individuals (MZ twins)
allograft
between different members of the same species
xenograft
between different species
what mediates tissue rejection?
immune system, specifically lymphocytes
MHC compatibility and graft survival
increased compatibility = increased survival
graft that differ at multiple loci rejected as quickly as those that only differ at MHC H2
direct allorecognition
host T cell recognizes graft MHC as foreign
indirect allorecognition
host APC processes graft antigen and presents to host T cells
hyperacute rejection
- due to preformed antibodies reacting to allogenic endothelium
- results in activation of complement and rapid intravascular thrombosis/necrosis
acute rejection
cellular= CD8 T cells react to alloantigens
humoral= antibodies are reactive as well
overall- parenchymal cell damage, interstitial and endothelial inflammation
chronic rejection
T cells produce cytokines that cause inflammation and proliferation of vascular smooth mm = occlusion
which type of rejection is the m/c cause of graft failure?
chronic
which organ has the highest 1 and 5 year survival rates?
kidney
which organ has the highest 10 yr survival?
liver
MOA of cyclosporin, tacrolimus
calcineurin inhibitors that block activation of NFAT
MOA of mycophenolate
inhibit guanine nucleotide synthesis (inhibit DNA synthesis)
MOA of rapamycin
inhibit mTOR and IL-2 signaling
MOA of antithymocyte globulin
binds/depletes T cells by phagocytosis or complement activation
MOA of Anti-IL-2R antibody
blocks Il-2 binding to receptor, may also be opsonin and help eliminate cells expressing IL-2R
MOA of CTLA-4 Ig
blocks CD28 from binding to B7 (blocks costimulation)
MOA of Anti-CD52
promotes complement mediated lysis of lymphs
which medication is used to treat acute rejection?
antithymocyte globulin
MOAs of corticosteroids (5)
- decreased NOS
- decreased adhesion molecules
- increased endonucleases
- decreased PL-A, COX2/increased annexin-1
- decreased IL-1, TNFa, GM-CSF, IL-3, IL-4, IL-5, CXCL8 (decreased inflammation)
when does GVHD occur?
when allogenic bone marrow transplants are contaminated with mature T cells