Graft quality and immunogenicity are key determinants of successful transplant outcome. While much of transplant immunology focuses on recognition of foreign donor antigen by the adaptive immune system, the intensity of host alloimmune response after engraftment is strongly influenced by contextual signals provided through innate mechanisms. Innate immunity priming is initiated during the donor injury and likely further magnified by the procurement process and ischemia/reperfusion injury. In addition, during inflammation and injury all cell types are capable of acting to trigger T cell action, co-stimulate immune responses, and produce inflammatory cytokines that can further escalate the immunogenicity. Under these inflammatory conditions, the graft is not only the target, but also directly activates the recipient adaptive immune response. Our research will investigates the effect of normothermic machine perfusion on sequential changes that occur as a result of the multiple injurious insults during the process of organ donation and procurement. Potential mechanisms include cytokine production, expression of TLRs and activation of other DAMP pathways, changes in barrier function and cell trafficking, and alteration in MHC molecule expression and antigen processing by inflamed tissue.