The immunology of transplantation

Solid organ transplantation represents a life-saving or prolonging therapy for hundreds of thousands of patients worldwide. Placement of an immunologically foreign graft into the recipient inevitably provokes an immune response, as donor-specific antigens are recognized by the host adaptive immune system. In addition, during the transplant procedure, the organ is rendered temporarily hypoxic, with attendant cellular damage, resulting in activation of the innate immune system by damage-associated signals. Here, we provide an overview of innate and adaptive immune responses to the allograft, including the cells and receptors required to respond to danger signals or graft antigens, and the molecular processes involved in generating alloantigen-specific B and T cells. We will also discuss the effector mechanisms by which cellular and humoral alloimmune responses damage the allograft and consider how transplant tolerance may be achieved. Finally, we describe emerging data implicating factors beyond the graft, including the microbiome, in susceptibility to rejection.