Transplantation (Denzin) Flashcards
Syngeneic Transplant
Identical Twin donor-recipient
Allogeneic Transplant
Random person donor–>recipient
Xenogeneic Transplant
Animal–>human
First and Second Set Allogeneic Graft Rejection
If graft rejected (first set), within two weeks immune cell migration causes necrosis, thrombosis, damage blood vessels at site. In second set, if get another graft from same source, same rejection but faster and stronger
Alloantigens/Xenoantigens
Allograft/xenograft antigens recognized as foreign and rejected
Alloreactive/xenoreactive T/B-cells
T/B-cells that target allo/xenoantigens
MHC I Alleles
HLA-A, B, C
MHC II Alleles
DHQ, P, R
Why are donor MHC molecules responsible for graft rejection?
Donor MHC can resemble recipient MHC-foreign peptide complex, so T-cells cause necrosis
Direct Recognition of Alloantigens
Dendritic cells in grafted tissue migrate to lymph node, present alloantigens to T-cells, causing reactive T-cells to graft and kill it
Indirect Recognition of Alloantigens
Transplant cells’ MHC or other antigens ingested by recipient dendritic cells, expressed on self MHC-1, activates CD4 T-cells to cause inflammation and rejection
Hyperacute Graft Rejection (1)
- Reject within minutes
- Circulating antibodies recognize graft cell antigens
- Could be from blood type mismatch, Rh mismatch, etc.
- Uncommon (since we’re smart enough to match right)
Acute Graft Rejection (2)
- Reject within days/weeks
- Mediated by alloreactive T-cells or antibodies (either direct or indirect alloantigen recognition)
- Treat with immunosupression of alloreactive T-cells
Chronic Graft Rejection (3)
- Reject over months/years
- Graft fibrosis and arteriosclerosis (blood vessel narrowing)
- Caused by alloreactive T-cells secreting cytokines stimulating fibroblast and VSM cells in the graft
- Main cause of graft failure, haven’t solved
Cyclosporine and Tacrolimus
- Immunosuppressor
- Inhibit calcineurin, preventing NFAT transcription, preventing T-cell cytokine production and thus immunosuppressive
Mycophenolate Mofetil
- Immunosuppressor
- Blocks lymphocyte proliferation by inhibiting guanine nucleotide de novo synthesis (only affects lymphocytes since other cells have salvage pathway, they dont)
Rapamycin
- Immunosuppressor
- Inhibits mTOR/IL-2 signaling, preventing lymphocyte proliferation
Corticosteroids
- Immunosuppressive
- Act on multiple immune cell types to downregulate inflammatory pathway
Antithymocyte Globulin
- Immunosuppressor
- Binds/depletes T-cells
Anti IL-2 receptor (CD-25) antibody
- Immunosuppressor
- Prevents T-cell proliferation by inhibiting IL-2 signaling (normally causes T-cell growth)
Belatacept (CTLA4-Ig)
- Immunosuppressor
- Acts as exogenous CTLA4, binding up B7 preventing costimulation by CD-28 T-cell receptor
Graft Vs. Host Disease (GVHD)
If mature allogeneic T-cells transplanted as part of hematopoetic stem cell transplant, they attack the recipient’s tissue (reverse of graft rejection)
- Host immune system can usually overcome, unless prior immunosupressed
- Same deal if immunosuppressed person gets whole blood transfusion- donor T-cells can attack
Autologous Transplant
Self donor–>Self recipient
