Figure 2.

Involvement of innate and adaptive immunity in development of damage to the transplant. Ischemia reperfusion injury (IRI) leads to induction of necrosis of tubular cells and release of damage associated molecular patterns (DAMPs), which are normally hidden within intact cells. DAMPs bind to Toll-like receptors (TLRs) on dendritic cells (DC) and induce their activation and maturation. The matured DC present donor-derived HLA antigens and co-stimulatory molecules to naïve T cells, which drives T cell differentiation into IFNγ producing TH1 cells. IFNγ can stimulate maturation of other DCs, induce macrophage activation and recruitment, and direct differentiation of CD8⁺ T cells. The recipient DCs are also able to capture and present donor HLA antigens, and thereby stimulate recipient CD8⁺ T cells. IRI can lead to induction of a local increase of complement component 3 (C3). Cleavage of C3 by the alterative pathway results in C3b deposition on the cell membrane and complement cascade activation. The small fragments C3a and C5a, released during complement activation, have pro-inflammatory effects. The formation of membrane attack complex (MAC) leads to target cell lysis and release of DAMPs.