Define allograft

• infiltrate of monocytes and lymphocytes
• T cells required (individuals deficient in T cells do not reject)
• immunosuppressed recipients have delayed or no rejection response

• first set- build up "memory" cells (takes 14 days) after first allograft
• second set- accelerated rejection that can be adaptively transferred (CD4 involved)
  • can transfer "memory" cells to different person

• direct- T cell recognized unprocessed allogeneic MHC molecule on graft APC
• indirect- present processed peptide on allogeneic MHC molecule bound to self MHC molecule

1. mix donor serum with recipient serium
2. look for Ab's to each other in cell
3. add trypan blue dye
   1. if uptake, cell membrane have been damaged
   2. if dye excluded, cell membrane in tact

• ABO bloodtype
• crossmatch
• HLA/MHC

• serologic
  • Ab to known MHC antigens
  • complement mediated cytotoxicity
  • detect mailny HLA-A, HLA-B, HLA-C and some HLA-DR and HLA-DQ
• cellular assay (MLC)
• DNA typing

1. put responder cells from MHC-A mouse with irradiated stimulator cells from MHC-A mouse in a test tube
2. see if they react (T cells do not react in this situation)
3. However, if the stimulator cells were from an MHC-B mouse, T cells would respond

1. cadaveric
   1. brain death
   2. heart beating vs. non-heart beating cadavers
2. live donor
   1. established (kidney)
   2. emerging (liver)
   3. investigational (lung)

hyperacute

acute

chronic

graft vs. host

How do you avoid hyperacute rejection?

Role of MHC in T cell response to alloantigens

Donor APC present antigen in nonself MHC to host immune cells, leading to MHC antigens on allograft acting like self-MHC binding to foreign antigen, which will activate T cells

Mechanism of action of chronic rejection

• narrow vasculature
• slow infiltration of immune cells
• takes months to years

• attack on host cells by immunocompetent cells in graft
• two to three wks after transplant

• active immune attack
• T cells + Ab's cause localized tissue injury and inflammation
• takes days to wks
• repeat episodes are common

• calcineurin inhibitors (ex: cyclosporin) along with anti-proliferative and steroids
• better off treating the prevention of rejection rather than treating once rejection occurs
• significant variation by organ and center

• calcineurin inhibitors
  • cyclosporin
  • tacrolimus
• antimetabolites
  • Azathioprine
  • Mycophenolate mofetil
• glucocorticosteroids
• TOR inhbitors
  • sirolimus