Transplantation Flashcards
What are the 3 phases of immune response to transplanted graft
• Phase 1: recognition of foreign antigens
• Phase 2: activation of antigen-specific
lymphocytes
• Phase 3: effector phase of graft rejection
which components does the body recognise as foreign
Most relevant protein variations in clinical transplantation
– 1. ABO blood group (for ABO-incompatible transplantation)
– 2. HLA (human leukocyte antigens)
• Some other determinants – minor histocompatibility
genes
what are the two major components of rejection
• Two major components to rejection:
– T cell-mediated rejection
– Antibody-mediated rejection (B cells)
what is HLA class I and II
HLA Class I (A,B,C)– expressed on all cells • HLA Class II (DR, DQ, DP) – expressed on antigenpresenting cells but also can be upregulated on other cells under stress
How does HLA disparity cause rejection
T cell mediated
antibody mediated
and b cell mediated
what are the phases of t cell mediated rejection
Phase 1 - presentation of donor HLA by a professional
antigen presenting cell (APC), in the context of
recipient HLA
Phase 2 – T cell activation, inflammatory cell
recruitment
Phase 3 – effector phase (organ damage by cytotoxic t cells or monocytes/macrophages
what are the mechanisms of antibody mediated rejection
Phase 1 – B cells recognise foreign HLA
Phase 2 - proliferation and maturation of B
cells with anti-HLA antibody production
Phase 3 – effector phase; antibodies bind to
graft endothelium = intra-vascular diseas
how does cytotoxicity assays work
if there is antibody binding and complement mediated cytotoxicity the stain will stain orange (ethidium bromide)
how does flow cytometry work
does the recipient’s serum bind to the donor’s lymphocytes
(bound antibody detected by fluorescently-labelled anti-human - ditection of labelled antigen
how does solid phase assays work
does the recipient’s serum bind to recombinant single HLA molecules attached to a solid support such as beads (bound antibody detected by fluorescently-labelled anti-human Ig)
how is rejection detected
• Detect rejection: monitor transplant function (creatinine) + screen
for antibodies
– If creatinine goes up: take a biopsy to confirm and classify rejection
how is rejection prevented
Prevent rejection with baseline immunosuppression
– Induction agent
• T-cell depleting: OKT3/ATG, anti-CD52
• Other: anti-CD25 (anti-IL2R)
– Base-line immunosuppression: CNI inhibitor + MMF or Aza, with or without
steroids
how is rejection treated
Treatment of rejection:
– T-cell: steroids (MP IV 3x 60mg/kg then oral), ATG/OKT3
– Antibody-mediated: IVIG, plasma exchange, anti-C5, anti-CD2
