How the Immune System Discriminates Infectious Nonself from Noninfectious Self

Abstract

It is abundantly clear that the complex of host defense systems now known as the immune system arose in evolution to provide the host with defense against infectious agents. All host defense reactions involve three components. First, the foreign material must be recognized by some mechanism that discriminates it from self. Second, a response must be initiated. Third, that response must lead to the removal of the foreign material from the body. In this paper, I wish to make three points about the host system of defense. First, the removal or final effector system are the same for both innate and adaptive immune responses. Second, I argue that the adaptive immune response arose through the development of clonally distributed receptors encoded in rearranging genes and utilizes these receptors to regulate existing innate defense mechanisms. Third, I want to show that these two classes of responses are also linked at the recognition and response phase, in that adaptive immunity utilizes an older, nonclonal system of recognition to discriminate the infectious from the noninfectious, as well as its clonally distributed receptor to discriminate nonself from self. Thus, one can see that the immune response discriminates infectious nonself from noninfectious self. Without both of these types of recognition event, responses fail to occur. This has important consequences both for host defense and for the avoidance of autoreactivity [1].

Supported by Grants NIH Al-26810 and the Howard Hughes Medical Institute