Physiopathology of acute and chronic rejection

Abstract

Allograft rejection is defined as tissue injury produced by the effector mechanisms of the alloimmune response, leading to deterioration of graft function. There are two types of rejection: T-cell-mediated rejection (TCMR) and antibody-mediated rejection (AMR). Both types of rejection can be early or late, fulminant or indolent, as well as isolated or concomitant and can share pathologic features on biopsy. The immune response to an allograft is an ongoing dialogue between the innate and adaptive immune system, which if unresolved will lead to rejection of the transplanted cells, tissues, or organs. Activation of elements of the innate immune system, triggered by tissue injury sustained during cell isolation or organ retrieval and ischemia reperfusion, will initiate and amplify the adaptive response. T cells require a minimum of two signals for activation: antigen recognition and co-stimulation. Antibody-mediated rejection triggered by alloantibody binding and complement activation is increasingly recognized as a significant contribution to graft loss. Even though one component of the immune system may dominate and lead to rejection, this is usually multifactorial, resulting from the integration of multiple mechanisms. Identifying the molecular pathways that trigger rejection facilitates the identification of targets for the development of immunosuppressive drugs.