This is often via direct antigen presentation of donor HLA via donor APC to recipient CD4+ T-cells also via CD8+ cells recognising foreign HLA
- APC secrete IL-12 to cause Th1 proliferation IL-2 to ^ NK cells, IL-3 to ^ HSC, INF-y to inhibit Th1 production, ^ MHC and activate NK cells
- APC secrete IL-10 to cause Th2 proliferation, these produce IL-3 to ^ HSC, IL-4 ^ IgE, IgE antibodiy switching in B-cells, ^ T-cell growth, ^ mast cells, IL-5 to ^ Eosinophils and activate B-cells
- CD8+ secretes INF-y to ^ MHC, activate NK, Inhibit Th2, TNF-a causes macrophages to induce apoptosis by increasing NO synthesis, perforin causes cell lysis
This occurs longer term and is via in-direct antigen presentation of donor shed HLA via recpient APC to CD4+ T-cells.
Normally a thickening of interlobular arteries (lipid laden macrophages, odema).
- Blood type (Checking donor and recipient)
- HLA compatibility (ELISA, cross-match in serum+complement, flow cytometry)
- Rituzimab, Plasmaphoresis, High dose IgG (remove antibodies in sensitized patients)
- Cyclosporine inhibits calcineurin and therefore T-cell activation is suppressed
- Azathiorpine prevents proliferation of T-cells
- Rapamycin inhibits cell cycle
- Mabs prevents activation of T-cells via IL-2 receptor
Risks: Tissue Ischemia, more chance of perfusion injury when blood supply and oxygen restored. Also cutting may induce inflammatory response (neutrophils - proinflammatory cytokines)