MICR2221 Transplantation

autograft

graft of one site to another in same individual (autologous/syngeneic tissue)

allograft

transplant from unrelated individual of same species (aka. homograft)

(allogeneic tissue)

xenograft

tranplant using tissue of diff species (xenogeneic tissue)

acute rejection

rejection within 14 days e.g. allograft w/o immunosuppressive drugs

chronic rejection

rejection after months (allograft when use immunosuppression)

what graphs is hyperacute rejection observed (within hours)

xenografts

is a second allograft rejected even quicker

yes

if give mouse t cells and it enhances rejection is true?

yes

what mediates accute rejection

MHC and t cells

what are nude mice

those that lack t cells

what are alloantigens

antigens that differ between a species (generate an alloreactive response)

what is the major souce of alloantigens and why

the mhc locus, are the most polymorphic

polygenic vs polymorphic

affected by multiple genes, multiple structures observed

are mhc alleles co-dominant

yes(both alleles expressed e.g. mother and father mhc)

direct allorecognition

APCs present in the grafted tissue migrate out of the graft and into reciprient lymph nodes where they engage with reciprient t cells (allo-MHC-recipient t cell interaction)

so host attacks graft

indirect allorejection

allogenic mols are processed directly by the reciprient APC and pres to reciprient t cells

t cells cant attack graft directly

t cells instead activate recipient macrophage (pres graft peptides) which then cause inflamm, tissue damage and pot ab response (alloantibodies)

how damage graft

CD8 from direct recognit attack

Cd4 from indirect stim b cells to prod ab (therefore complement and adcc) and help macrophage become activated

when does direct and indirect allorecognition occur

if t cells recognise foreign mhc on APCs in graft then direct

if they dont, then indirect, where host cells pres foreign peptides to t cells, but t cells arent comp so cant bind so have to sim b cells that can prod ab against graft.

why may some foreign mhc be recognised

specific shape of mhc req recognis may be partly formed by the peptide it presents, which might look like host mhc, so t cells can recognise it

what do immunosuppressive drugs target

key steps in t cell activation

used to deplete grafts of immune cells