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Flashcards in Transplant Deck (20)

MHC and transplant

-there is MHC class I- HLA-A, B, C, D, E, F, G
-there is MHC class I- HLA-DM, DO, DP, DQ, DR
-some are highly polymorphic, some aren't as much, some are harder/easier to match


Blood Group Antigens

-blood in the most common transplant
-blood groups are antigens of the surface of most cells of the body. Most people have "natural" antibodies against other blood groups
-they differ by one carbohydrate
-O has anti-A, and anti-B antibodies
-A has anti-B, B has anti-A, AB- no antibodies
-also have to deal with Rh
-ABO method agglutionation


Hyperacute rejection

-the most severe and immediate type
-caused by preformed antibodies
-most common is blood group antigen
-also could have pre-existing HLAs-
-antibodies against donor blood group antigens bind vascular endothelium of graft, initating an inflammatory response occlude blood vessels -> graft is engorged and purple because of hemorrhage


Cross Match

-antibodies to HLA
-IgG antibodies
-from previous transplant
-a lot of blood transfusions
-women give birth


Panel Reactive Antibody

-the serum of a recipient is tested against a panel of leukocytes from many individuals- how many wells do they have reaction
-detection of the presence of antibodies to HLA
-presented as percentage-0-100%, low value less likely to react


Acute rejection

-T cells from recipient become reactive against the transplant
-takes to week
-stronger response to donor cells expressing MHC II- present in graft and elicit a strong immune response
-second is indirect with presentation of dead donor cell by host APCs
-most immune suppression therapies are directed towards inhibiting acute rejection


Chronic rejection

-takes months or years and is primarily the result of indirect recognition of the transplant.
-it may be to MHC molecules or towards other minor transplantation antigens
-associated with the presence of antibodies to HLA-class 1 antigens in the graft which seem to act on the vasculature of the graft


Matching HLA

-not critical to survival
-when possible matching is done, when critical blood type matching will suffice
-0 mismatches- 13.4 half life, 6 misses- 8.9 halflife


Testing at transplantation

-Repeat ABO on donor
-HLA I and II on donor
-find match on computer net
-cross match on all positive sera from antibody screening


Workup for transplantation- HLA I

-HLA Type I
-should find 6 type I antigens unless there is homozygosity
-2A loci, 2B loci, 2C loci


Workup for transplantation- HLA II

-panal reactive antibody
-mixed lymphocyte reaction
-molecular techniques


Anti-ABC antibody testing

-Anti-HLA-ABC testing done monthly
-presensitization by graft, transfusion, pregnancy
-used for cross-matching against donor lymphocytes



-these relatives of cortisol interfere with a transcription factor needed to turn on the genes for T cells to become activated
-knock out T cells
-prednisone and prednisolone
-decrease IL-1, 3, 4,5 CXCL8- decrease inflammation, also decrease adhesion molecules etc


Cytotoxic drugs

-interfere with DNA synthesis
-interfere with the rapid cell proliferation needed for immune responses
-Azathrioprine- purine analog


FK506 and cyclosporine

-natural product isolated from microbial cultures
-inhibit signaling pathway used by T cells to turn on their genes for activation, IL-2 secretion
-FK506 is known as tacrolimus, cyclosporine is Neoral


Antilymphocyte (thymocyte) globulin

-contains antibodies raised in rabbits or horses directed against T cells


Monoclonal antibodies

-several preparations
-Muromonab-CD3 (OKT3) and humanized anti-CD3 monoclonals, which can bind to the CD3 molecule on the surface of T cells
-Daclizumab and basiliximab both target the IL-2 receptor and thus inhibit only activated T cells


new stuff-CTLA-4-IG

-protein produced by recombinant DNA technology that combines
-the extracellular portion of CTLA-4 one of the ligands for B7 with the Fc region of human IgG1
-it blocks co-stimulation of T cells- as effective and less toxic than cyclosporine


Downside of Transplantation rejection Therapies

-Infections: bacterial, fungal, viral, parasitic
-transplant rejection: recipient's T cells attack the transplant
-when bone marrow is transplanted the T cells in the transplant attach the recipient's tissue: graft vs host disease


Graft vs host

-allogenic bone marrow transplant contains mature and memory T cells
-T cells circulate in blood to secondary lymphoid tissues
-alloreactive cells interact with dendritic cells and proliferate
-effector CD4 and CD8 T cells enter tissues inflamed by the conditioning regiment and cause further tissue damage
-you could remove T cells from transplant
-sometimes GVH not bad- kills residual tumor, small amount good for aiding engraftment