Flashcards in Transplantation Deck (19):
Is HLA matching important for solid organ transplants?
Before cyclosporine and other immune suppressive drugs it was but now it's not considered necessary for many types of organ transplants.
However, MHC matching is still important for HSCT.
What is an alloantigen?
genetically determined to be in some individuals of a species
When recipient T cells directly see alloantigens on donor APC
Responsible for acute graft rejection
When donor alloantigens are taken up and processed by recipient APC and presented to recipient T cells
Responsible for later stages of allograft rejection
Another individual of the same species
Mixture of donor and recipient cells
Major barrier to xenotransplantation, occurs within minutes
Complement activation, endothelial damage, inflammation and thrombosis
Can be cellular or humoral in nature; typically occurs within days to weeks in non-immune suppressed individuals or months-years in immune suppressed.
Parenchymal cell damage, interstitial inflammation
Major cause of graft failure (b/c of improvements in treatment for acute)
Occurs within months to years, vascular changes, interstitial fibrosis, loss of renal parenchyma; get renal ischemia due to loss of glomeruli, interstitial fibrosis and tubular atrophy.
Chronic inflammatory reaction in vessel wall, intimal smooth muscle cell proliferation, vessel occlusion.
Name some drugs that help prevent graft rejection.
Anti-IL-2 receptor antibody
What must a patient undergo before HSCT?
Chemotherapy and/or irradiation to eliminate malignant cells and make space for incoming cells
What are minor histocompatibility antigens (miHA)?
Less potent at inducing graft rejection; Cleaved and processed endogenous proteins that occupy the binding groove of MHC class-1 and class-2 molecules
Contain genetic polymorphism-- usually due to SNPs. Can be either MHC class-1 or class-2 restricted.
What is the mixed lymphocyte reaction?
A way in culture to measure alloreactivity and mimics what happens in vivo
Explain acute GVHD.
Results from reactivity of donor T cells against histocompatibility antigens of the recipient. In acute GVHD, mature T cells in donor graft recognize and react against host antigens, creating a potentially fatal immune response.
Explain chronic GVHD.
Late complication (>100d) with autoimmune-like features; thought to be from cytokine and T cell dysregulation.
Explain graft vs tumor effect.
Graft contains donor T lymphocytes that are beneficial for recipient because they eliminate residual host T cells or tumors. Develops after recognizing tumor-specific or recipient-specific alloantigens.