Mechanisms of Allograft Rejection and Tolerance/Immunosenescence

All transplanted allografts undergo immune-mediated rejection unless the recipient immune response is modified in some way. Induction of immune tolerance is an oft-touted goal in the field of organ transplantation. This chapter highlights the mechanisms of rejection after organ transplantation and provides an overview of the predominant mechanisms by which tolerance is induced and maintained. Also, it sheds some light on the differences in operational tolerance among various organs, highlighting emerging knowledge from heart and lung transplantation. Different organ allografts have different propensities to be spontaneously accepted without any treatment. Also, intrinsic and extrinsic factors of every organ can play a role in spontaneous tolerance. Recent studies have highlighted that rejection after lung transplantation may start with the activation of innate immune pathways in response to early graft injury. Understanding the mechanisms that underlie the organ-specific differences in transplant tolerance has important clinical relevance.