Transplant Immunology Flashcards
Isograft
Identical to self
Allograft
Between individuals of the same species
Xenograft
Between species
First phase of the alloimmune response
Inflammation caused by reperfusion injury and surgical trauma. These things contribute to free radical formation, which causes release of DAMPS, activating complement and TLRs. Innate immune response. Also promote transmigration of T cells.
Are MHC’s the targets of transplant immunity?
Yes
Alloreactive antibodies
Directed at the polymorphic regions of different MHC’s, can develop through transplant, pregnancy, cross reactivity. Mostly Th1 and IgG.
Alloreactive T Cells
Directly recognize donor MHC’s. Occur due to cross reactivity. Created from exposure to viral proteins that look like different MHC’s, can’t be direct, because T cells are already activated.
Direct Recognition By Alloreactive T cell
Recipient T cells directly recognize the donor APC, because they have been activated by cross reactivity.
Indirect Allorecognition
Recipient APC expresses donor peptide (from their digested HLA’s). Less frequent.
Does MHC matching prevent rejection?
No, there are minor histocompatibility proteins
Why can’t females respond to male donations?
Y chromosome minor histocompatibility proteins.
What do drugs in transplantation do?
They block costimulation and expansion of T cells.
CD62 hi CD44 lo T cells, vs CD62 lo CD44 hi T cells
In LN’s, in tissue.
Alloantibody effector function
Bind to donor HLA, cause compleent activation, cause microthrombi to form.
Hyperacute rejection
caused by ischemia secondary to antibody induced microthrombi
T Cell effector mechanisms
Cytokine production, delayed type hypersensitivity. Type IV, cause macrophage activation. Cytotoxicity.
How can acute rejection be monitored clinically?
Decrease in kidney function (rise in creatinine), caused by T cells responding via direct pathway.
Immunosuppression
is non specific, but primarily targets T cells, not b cells. Can cause kidney fibrosis and susceptibility to infection.
Tolerizing Mice Experiment
Fetal mice injected with cells from another strain of mouse didn’t reject the organ of the same mouse.
Acquired Transplant Tolerance in humans?
Give BM with graft, block costimulators, expand T regs.
