Transplantation Flashcards
5 pages, lecture 12
describe allogenic transplant reactions
may be from a cadaveric, living related, or living unrelated donor.
primes the immune system. if it is rejected and another transplant is made from the same donor, this results in a more repid, second-set reaction. caused by a memory immune reponse from clonally expanded and primed T cells.
3 mechanisms of rejection?
hyperacute, acute or chronic.
can be mediated by antibody or T cells. T cells through direct recognition of donor MHC or indirect recognition of antigen presented by self MHC.
describe hyperacute rejection
very rapidly, a few minutes or hours.
due to a preexisting antibody such as with ABO.
rejected rapidly as ABO are on the endothelium and the RBCs.
complemet activatin and leakage of fluids. platelet aggregation blocks microvasculature.
takes place with xenotransplants ie pigs as we mak IgM and IgG to modified sugars on pig tissue.
these transplants are termed DISCORDANT.
also the decay accelerating factor (DAF0 does not work on pig tissue hence complement is disinhibited.
describe generally acute graft rejection
the main immunological barrier to autotransplantation. caused by T cell recognition either direct recognition or indirect recognition. not an issue in blodd transplants as no MHC.
describe direct recognition of allo MHC in acute graft rejection
allogenic cells migrate from graft to lymph nodes and their MHC can activate T cells that are reactive to the allo-MHC. these are activated strongly and as they react to the allo MHC regardless of loaded peptides, they react strongly to the tissue, rejecting it.
describe INdirect recognition of allo MHC in acute graft rejection
uptake of allogenic proteins by recipient APCs, presentation by self MHC to T cells. these include minor/H antigens. these are proteins that vary in sequence and at least one of the allomorphs is found in a peptide which binds recipient MHC. MHC sharing between donor and recipient can increase reactivity as donor, as well as recipient, dendritic cells can prime the recipient T cells for these minor peptides.
This is slower than direct recognition but is additive, lost of minor difference increaes strength of response. example is male donor to female or vice versa. In human transplantation, recognition of male minor antigens can play an important role in haematopoietic stem cell transplants.
describe chronic rejection
can occur years after transplant. no improvement in its treatment over the last 30 years as the mechanism is obscure as its hard to research but may relate to immune response vs blood vessels - gradual ischaemia.
what are immunopriviliged sites?
no rejection. ie cornea
often due to no lymphatic drainage but sometimes also lack vascularisation.
sources of haematopoeitic stem cell trasnplants in order of decreasing mature T cell contamination
- peripheral blood (enriched via cytokine administration)
2 - bone marrow
3 - cord blood
many are autologous and exhibit no immunological problems
what’s the graft v host reaction
haematopeitic stme cell transplant. graft rejects host. useful in laukaemic patients - graft vs laukaemia
3 diferent examples of HLA matching on allograft survival?
1 - haematopoietic stem cells - very important
2 - significant - kidney, heart
3 - no effect - liver
is complete HLA matching common? how is it improved?
uncommon due to six polymorphic genes, 3 for each class, on each haplotype. each gene can exhibit one of different alleles.
- as theyre inherited in haplotypes however, the odds are improved with close relatives.
immunosuppression therapy for kidney transplants?
combination
1 - steroids - systemic, complex mechanism. prednisolone
2 - cytotoxic drugs - kill dividing T cells - azathioprine
3 - immunosuppressive - target lymphocyte cell signalling - cyclosporin
others - FK506, rapamycin.
immunosuppression must be lifelong or the organ will be damaged.
5 year graft survival of 6 tissues?
1 - lung - 35% 2 - liver - 45% 3 - heart and cornea - 70% 4 - bone marrow - 80% 5 - kidney - 85%
