Transplantation and Transfusion Reactions Flashcards
what is an autograft
self tissue transferred from one body site to another in an individual
what is an isograft? (syngeneic graft)
tissue transfer between genetically identical individuals
what is an allograft?
allogeneic graft, tissue transfer between genetically different members of the same species
what is a xenograft?
tissue transfer between members of different species
what does rejection time depend on?
tissue involved – skin grafts occur faster and more often than others
describe the basic steps of rejection?
- revascularization followed by immune cell tissue infiltration by lymph, PMN, monocytes
- decreased vascularization as a result of the immune activity
- tissue necrosis within 2 weeks, rapid rejection occurs if 2nd transplant attempted (memory)
what type of reaction is a hyperacute rejection?
type II
what mediates hyperacute rejections?
preexisting, circulating antibodies that bind to blood group Ag within capillaries of the grafts
what category does ABO reaction fall into?
hyperacute reaction - type II
why is blood typing important for organ transplants?
ABO blood group Ag are present on RBC AND endothelial cells of donor organs, and Ig against these Ag can destroy the organ
what is the mechanism of hyperacute rejection?
IgG binding recruits C1q for complement activation and fixation. C3a/C5a recruit neutrophils and macrophages which promote inflammation. macrophage releases platelet activation factor which causes platelet aggregation, and blood clots form. clots prevent vascularization of the graft and ischemic necrosis develops.
how are pre-existing Ig against alloAg made?
blood transfusions or previous organ transplant can induce Ig against HLA of donor cells
how are MHC possible alloantigens?
each person expresses MHC proteins that can seem foreign due to MHC restriction in the thymus. (T cells are trained to recognize Ags displayed only on the person’s specific MHC mol, other MHC = alloAg
which MHC types are most likely to be recognized as alloantigens
HLA-A, HLA-B, HLA-DR
other than MHC, what other protein is targeted in rejection?
minor histocompatibility Ag (mHA) aka non-MHC antigens
could be glycoproteins
what is an example of mHA rejection reaction?
blood transfusion mismatches
what is the first step of acute rejection>
direct recognition of alloantigens by alloreactive T cells (CD4 and CD8) reacting to allogenic APC with allogeneic MHC
what is normal t cell activation
TCR recognition of self MHC and peptide leading to normal T cell activation (MHC and peptide both fit normally)
what the 1st option for recipient T cell activation to graft
T cell recognizes allogeneic MHC molecule whose structure resembles the self-MHC foreign peptide complex. the TCR has actually bound the MHC structure itself, not the peptide. recognizes graft MHC directly
2nd option for recipient T cell activation to graft?
T cell recognizes a structure formed by both allogeneic MHC molecule and bound peptide. TCR recognizes both the graft MHC itself and the peptide.
what type of reaction is acute rejection?
type II and IV
when does acute rejection occur?
first few weeks after transplantation
what mediates acute rejection?
B and T cells
what is the principle cause of early graft failure?
immunosuppressive drugs given before and after transplant