The immune response is triggered by the interaction of an antigenic determinant with specific receptors on lymphocytes. It is calculated that there are several millions of different receptors in lymphocytes—1015–1018 on T cells and 1011 on B cells—sufficient to respond to a wide diversity of epitopes presented by microbial agents and potentially noxious ex-ogenous compounds. At the same time, the immune system has the capacity to generate lymphocytes with receptors able to interact with epitopes expressed by self antigens. Dur-ing embryonic differentiation and adult life the organism uses a variety of mechanisms to ensure that potentially autoreactive lymphocytes are eliminated or turned off. This lack of response to self antigens is known as tolerance to self.
When the immune system is exposed to exogenous compounds, it tends to develop a vigorous immune response. The discrimination between self and nonself is based the fact that the immune system has the ability to recognize a wide variety of structural differences on exogenous compounds. For example, infectious agents have marked differences in their chemical structure, easily recognizable by the immune system. Cells, proteins, and polysac-charides from animals of different species have differences in chemical constitution, which as a rule are directly related to the degree of phylogenetic divergence between species. Those also elicit potent immune responses. Finally, many polysaccharides and proteins from individuals of any given species show antigenic heterogeneity, reflecting the genetic diversity of individuals within a species. Those differences are usually minor (relative to differences between species) but can still be recognized by the immune system. Transfu-sion reactions, graft rejection, and hypersensitivity reactions to exogenous human proteins are clinical expressions of the recognition of this type of differences between individuals.