Transplant Immunology Flashcards
Two types of tests to perform before transplantation?
Compatibility (HLA)
Pathogens (HIV, Hep, Herpes, Syph)
What is an autograft?
Transplantation of self tissues to a different site on the body
What is a syngeneic transplant?
Transplant between genetically identical individuals
What is an allogenic transplant?
Transplant btw two genetically different individuals
What is a xenograft
Transplantation between different species
Cause of Allogenic immune responses?
Genetic Differences between how and recipient
Describe what happens in a hyperacute (immediate) reaction
Preexisting Abs to A/B antigen or MHC I/II in recipients bind endothelial cells of transplanted organs. Rejection.
What would cause a hyperacute reaction to MHC I/II?
Pregnancy, Blood Transfusion, or previous transplantation
A type A antigen ends in….
A type B antigen ends in…
A = GalNAc B = Gal
Name for the three rhesus factors we discussed?
C, D, E
Acute Rejection is…
Within Weeks
Effector CD4 TH1 Cells or CD8
Response to HLA differences between donor/recipient
How can acute rejection be prevented?
Immunosuppressive Drugs
anti-T cell antibodies
How does accelerated acute rejection (within days) happen?
Sensitized (memory) T cells from previous grafts/exposure
How does cross-reactive recognition for alloreactivity happen?
T cell recognizes an allogenic MHC molecule whose structure resembles the self MHC-foreign peptide complex.
Acute response to graft
Describe the process of T cell mediated graft rejection.
Donor Dendritic cells to the spleen
Activate recipient T cells
Graft Rejection
Describe the MLR (Mixed Lymphocyte Reaction) Test
Co-culture blood from donor and recipient. If theres a lot of proliferation or T cell mediated toxicity – its not a great match.
Describe chronic rejection
Months or Years after transplant
Thickening of BV walls –> Ischemia
Unclear Mech, Maybe Chronic DTH
In kidney transplant, it is especially important to match…
HLA A, B, DR
Describe the role of Minor Histocompatibility antigens in immune response
Minor HC are peptides are deriver from non-HLA I or II bodies. These are normally digested by the proteasome.
What three things must be true for GVHD to occur?
Graft must contain immunocompetent cells (T cells)
MHC Mismatch
The recipient must be incapable of rejecting the graft
How does GVHD happen?
Allogenic bone marrow transplant with mature T cells is transferred in. T cells circulate in the blood to secondary lymphoid tissues, where alloreactive T cells interact/proliferate. Effector CD4 and CD8 T cells enter tissues inflamed by the conditioning regimen.
Three potential cons of GVHD
- Donor-derived lymphocytes attack host tissues
- Non-functional T cells due to MHC mismatch
- Failed reconstitution
Alternative BMT sources to minimize GVHD.
Autologous BMT: Use self marrow obtained before radiation
Umbilical cord blood cells (w/ hematopoetic stem cells)
Isolated stem cells free of T cells
Explain how NK cells can mediate a graft versus leukemia response
Haploid transplant in which one of the two HLA-C ligands matches. Donor hematopoetic cells safe from NK cells, but recipient cells (including any spare leukemia) are killed by NK.
