How the Immune System Discriminates Infectious Nonself from Noninfectious Self
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 .
KeywordsInfectious Agent Adaptive Immune Response Clonal Expansion Immunological Memory Howard Hughes Medical Institute
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- 2.Burnet FM (1959) The clonal selection theory of immunity. Vanderbilt University Press, NashvilleGoogle Scholar
- 4.Linsley PS, Brady W, Grosmaire L, Aruffo A, Damle NK, Ledbetter JA (1991) Binding of the B cells activation antigen B7 to CD28 costimulates T cell proliferation and IL-2 mRNA accumulation. J Exp Med (in press)Google Scholar
- 5.Liu Y, Janeway CA Jr (1991) Microbial induction of co-stimulatory activity for CD4 T cell growth. Int Immunol (in press)Google Scholar
- 6.Steinman RM, Metlay J, Bhardwaj N, Freudenthal P, Langhoff E, Crowley M, Lau L, Witmer-Pack M, Young JW, Pure E, Romani N, Inaba K (1989) Dentritic cells: nature’s adjuvant. In: Janeway CA et al. (eds) Immunogenicity. Liss, New YorkGoogle Scholar
- 9.Liu Y, Janeway CA Jr Clonal expansion of normal CD4 T cells requires expression of both ligand and co-stimulator on one cell. (submitted)Google Scholar
- 11.Kawabe Y, Ochi A (1990) Programmed cell death and extrathymic reduction of Vß8+, CD4+ T cells in Staphylococcus enterotoxin B-specific tolerance. Nature (in press)Google Scholar