Immunological principles of acute rejection
Issa FG., Goto R., Wood KJ.
© Cambridge University Press 2011. The immune system has evolved to clear the host of invading microorganisms and its own cells that have become altered in some way, such as infected cells or mutated tumorigenic cells. The immune system recognizes such cells as “foreign” and the molecules they express as antigens. When organs are transplanted between genetically disparate (allogeneic) individuals, the immune system recognizes and reacts with the foreign antigens of the other individual (alloantigens) on the transplant (allograft) to cause rejection. This rejection response is the result of interplay between the host innate and adaptive immune systems. The innate response is mediated by cells and molecules that include macrophages, dendritic cells (DCs), granulocytes (neutrophils, basophils, and eosinophils), natural killer (NK) cells, and the complement cascade, as well as proinflammatory cytokines and chemokines (chemoattractant cytokines). It represents a preformed defense that is immediately available until a specific response can be mounted by the adaptive immune system. The innate response is less specific than the adaptive response and will be induced even if a transplant has been performed between genetically identical individuals (isograft), simply as a result of implanting or transplanting the cells or organ. Adaptive immunity is mediated by lymphocytes (T and B cells) and displays slower kinetics than the innate response. However, the adaptive response is specific to foreign antigens (alloresponse) and is therefore not activated by isografts. Although the innate immune response is important for the initiation of the alloresponse and can initiate tissue damage, it cannot alone cause rejection (in other words, the complete destruction of the tissue). On the other hand, the adaptive immune response is more damaging and is essential to rejection. The importance of the adaptive response is reflected in the observation that animals experimentally depleted of T cells cannot reject allografts.