Allograft Rejection Signaling

Allorecognition occurs when the host immune system detects same-species, non-self antigens; this is then the trigger for allograft rejection. Antigen presentation to the host immune system follows either the direct or indirect pathways.The direct pathway results from the recognition of foreign MHC molecules, intact, on the surface of donor cells. This activates host CD4+ or CD8+ T cells. If activated, CD8+ T cells progress to cytotoxic T lymphocytes (CTLs) which destroy donor cells. In contrast, CD4+ T cell activation leads to Th1 cells which then activate macrophages. Macrophages secrete cytotoxic molecules like TNF-α that destroy allograft cells.

Indirect allorecognition occurs when donor MHCs (and other proteins shed from the graft) are internalized, processed, and presented as peptides by host antigen presenting cells. This pathway predominantly activates CD4+ T cells which lead to Th2 cells. Cytokines secreted by Th2 cells activate B cells which secrete alloantibodies and destroy allograft cells via a complement mediated pathway.