ABSTRACT
Through clonal selection, the immune system is able to prepare and respond to a multitude of diverse antigens. However, since the generation of diversity is a stochastic post-germline encoded event, a critical component of the immune response must subsequently be the ability to discern between harmful and innocuous antigens in a tolerance process. Early theories, (on which the foundation of modern immunology is based) described tolerance as the ability to distinguish self from nonself. In the beginning, Ehrlich and Morgenroth realized this important aspect of the system and coined the term “horror autotoxicus” to describe the consequences of tolerance being broken and the immune system unleashing its effector function on one’s own body. 1 Burnet proposed that this educational skewing toward the recognition of only nonself occurred during a critical developmental period that began in utero and lasted through the perinatal period. 2 During this time, autoreactive lymphocytes would recognize self antigens and be deleted. If indeed self was defined during a critical developmental period, then a prediction of such a model was that “foreign” antigens introduced during this period would induce tolerance. Experiments by Billingham demonstrated that if cells from A mice were injected into B mice during the fetal period, the B mice would accept A-strain skin grafts but reject third party C-strain grafts. 3 Inversely, Triplett was able to show that by removing the pituitary anlage from tree frog larvae and then replacing the adult animals with their own pituitaries, the frogs rejected the autografts. 4 Since the pituitary was not present during the critical self education period, it was seen as foreign in the adult animal and rejected.
