A biological context for the self-nonself discrimination and the regulation of effector class by the immune system.
An effective immune response to an antigen requires two sets of decisions: Decision 1, the sorting of the repertoire, and Decision 2, the regulation of effector class. The repertoire, because it is somatically generated, large, and random, must be sorted by a somatic mechanism that subtracts those specificities (anti-self) that, if expressed, would debilitate the host, leaving a residue (anti-nonself) that, if not expressed, would result in the death of the host by infection. The self-nonself discrimination is the metaphor used to describe Decision 1, the sorting of the repertoire. In order to be functional, the sorted repertoire must be coupled to a set of biodestructive and ridding effector functions, such that the response to each antigen is treated in a coherent and independent manner. Although a reasonably complete framework for Decision 1 exists, Decision 2 lacks conceptualization. The questions that must be considered to arrive at a proper framework are posed. It should be emphasized that manipulation at the level of Decision 2 is where clinical applications are likely to be found.
Cohn
Melvin
M
The Salk Institute for Biological Studies, Conceptual Immunology Group, La Jolla, CA 92037, USA. cohn@salk.edu
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D000941:Antigens / Q000276:immunology; D006801:Humans; D007107:Immune System / Q000276:immunology* / Q000378:metabolism; D017634:Self Tolerance / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism
D000941:Antigens