Transplantation Stuff Flashcards
Hyperacute (immediate) rejection reaction
caused by preexisting antibodies to ABO antigens and/or MHC molecules expressed by endothelial cells of transplanted organs
complement activation, endothelial damage, inflammation and thrombosis
Acute rejection (days)
caused by effector CD4+ Th1 cells or CD8 T cells that respond to different HLA differences between donors and recipients (similar to Type IV hypersensitivity)
minor histocompatibility leads to slower acute rejection
can be prevented by immunosuppressive drugs or anti-T cell antibodies
Chronic rejection (months/years)
thickening of blood vessel walls leads to ischemia
localized tissue anemia due to obstruction of arterial blood flow
chronic DTH reaction in vessel wall, intimal SM proliferation, vessel occlusion
GVHD (graft versus host disease)
caused by donor T cells in the graft (bone marrow) in immunocompromized hosts
T cells are reactive against recipient’s self antigens and attack recipient’s tissues
Cyclosporin A and Tacrolimus (FK506)
inactivate calcineurin (calcium binding protein)
prevents IL-2 transcription
leads to the suppression of T, B and granulocyte activation
high nephrotoxic
Corticosteroids: Prednisolone
binds to steroid receptor complex and induces expression of many genes (including IkB-alpha)
IkB-alpha inhibits NF-kB activation
side effects: fluid retention, weight gain, diabetes, loss of bone mineral, thinning of skin
Cytotoxic drugs
kill dividing drugs (specificity issues)
Azathioprine
inhibits DNA replication
kills lymphocytes but also all dividing cells in body
Cyclophosphamide
cross-links DNA
side effects includes damage to bladder
Methotrexate
prevents DNA replication by inhibiting thymidine synthesis
Anti-CD3 and mAB
prevents first signal from TCR-CD3::MHC:peptide complex
Belatacept
prevents second signal from CD28::B7
Basiliximab
prevents IL-2 from generating a T cell signal to proliferate
autograft
from self
syngeneic graft
from identical twin or clone
