Figure 1.

Mechanisms potentially involved in microvascular inflammation. HLA-DSAs can cause microvascular damage through activation of the complement system and recruitment of inflammatory cells such as NK cells and monocytes/macrophages via their crystallizable fragment (Fc) receptors, inducing antibody-dependent cell cytotoxicity. Many non-HLA allo- and autoantibodies have also been identified as players in allograft rejection. The exact mechanisms involved are still unclear but could be similar to those of HLA-DSA-associated processes. Recent studies have identified antibody-independent mechanisms involving the key role of innate immune cells distinguishing between self and non-self, leading to an alloimmune response: NK cell activation can render these cells apt to attack endothelial cells via a missing self-mechanism, while a SIRPα/CD47 mismatch between the donor and recipient can lead to monocyte allorecognition and monocyte-driven graft injury.