Inmunidad innata

The Ne w E n g l a nd Jo u r n a l o f Me d ic i ne

Review Articles

Advances in Immunology
IAN MACKAY, M.D.,
AND FRED S. ROSEN, M.D., Editors

I NNATE I MMUNITY
AND

beginning to emerge, and we expect them to contribute in important ways to our understanding of the body’s defense against bacteria, the way in which the adaptive immune system establishes long-lasting antimicrobialprotection, and some of the mechanisms used to avoid producing autoimmunity.
STRATEGIES OF INNATE AND ADAPTIVE IMMUNE RECOGNITION

RUSLAN MEDZHITOV, PH.D., CHARLES JANEWAY, JR., M.D.

T

HE immune system has traditionally been divided into innate and adaptive components, each with a different function and role. The adaptive component is organized around two classes of specialized cells, T cellsand B cells. Since each lymphocyte displays a single kind of structurally unique receptor, the repertoire of antigen receptors in the entire population of lymphocytes is very large and extremely diverse. The size and diversity of this repertoire increase the probability that an individual lymphocyte will encounter an antigen that binds to its receptor, thereby triggering activation andproliferation of the cell. This process, termed clonal selection, accounts for most of the basic properties of the adaptive immune system. Clonal expansion of lymphocytes in response to infection is absolutely necessary for the generation of an efficient immune response. However, it takes three to five days for sufficient numbers of clones to be produced and to differentiate into effector cells, whichallows more than enough time for most pathogens to damage the host. In contrast, the effector mechanisms of innate immunity, which include antimicrobial peptides, phagocytes, and the alternative complement pathway, are activated immediately after infection and rapidly control the replication of the infecting pathogen. For this reason, containing the infection until the lymphocytes can begin to dealwith it has long been considered the main function of innate immunity. However, it has become increasingly clear that the innate immune system has a much more important and fundamental role in host defense. In this article we will outline the ways in which the innate immune system interacts with and controls adaptive immune responses. The clinical implications of these discoveries are just

Fromthe Section of Immunobiology, Yale University School of Medicine, New Haven, Conn. Address reprint requests to Dr. Janeway at the Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, or to Dr. Medzhitov at ruslan@yale.edu. ©2000, Massachusetts Medical Society.

The main distinction between the innate and the adaptive immune systems lies in the mechanisms and receptorsused for the immune recognition. In the adaptive immune system, the T-cell receptor and the B-cell receptor are generated somatically, during the development of T and B cells, in a way that endows each lymphocyte with a structurally unique receptor. Since these receptors are not encoded in the germ line, they are not predestined to recognize any particular antigen. Rather, an extremely diverserepertoire of receptors is generated randomly, and lymphocytes bearing useful receptors (i.e., receptors specific for pathogens) are subsequently selected for clonal expansion by encountering the antigens for which they happen to be specific. These useful receptors, moreover, cannot be passed on to the next generation, even though they might give one’s progeny a survival advantage. No matter howbeneficial they may be, antigen receptors for common environmental pathogens have to be reinvented by every generation. Since the binding sites of antigen receptors arise as a result of random genetic mechanisms, the receptor repertoire contains binding sites that can react not only with infectious microorganisms but also with innocuous environmental antigens and self antigens. Activation of the...