Innate pathways of immune activation in transplantation

Abstract

Studies of the immune mechanisms of allograft rejection have predominantly focused on the adaptive immune system that includes T cells and B cells. Recent investigations into the innate immune system, which recognizes foreign antigens through more evolutionarily primitive pathways, have demonstrated a critical role of the innate immune system in the regulation of the adaptive immune system. Innate immunity has been extensively studied in its role as the host's first-line defense against microbial pathogens; however, it is becoming increasingly recognized for its ability to also recognize host-derived molecules that result from tissue damage. The capacity of endogenous damage signals acting through the innate immune system to lower immune thresholds and promote immune recognition and rejection of transplant grafts is only beginning to be appreciated. An improved understanding of these pathways may reveal novel therapeutic targets to decrease graft alloreactivity and increase graft longevity.

Figure 1

Infection and cell injury result in the production of PAMPs and DAMPs that promote the inflammatory response via TLRs located on the cell membrane and within endosomes. Cytoplasmic PAMPs activate similar pathways by binding to NOD1 and NOD2.

Figure 2

Liver injury during transplantation can convert an immunologically quiescent organ to an inflammatory organ that promotes acute rejection.