Melvin Cohn and Rodney E. Langman

The Salk Institute, P.O. Box 85800, San Diego, California, 92186-5800

Received 8/15/96; Accepted 9/9/96; On-line 10/1/96

2. INTRODUCTION

All organisms need mechanisms that provide protection against infectious pathogens. Prokaryotes and invertebrate eukaryotes have a variety of such mechanisms, including restriction enzymes, lectins, lytic peptides, phagocytes, etc.(1). We refer to these as defense mechanisms. Vertebrates also have these defense mechanisms, but, in addition, they have an immune system. Both defense mechanisms and the immune system must make a self-nonself (S-NS) discrimination because they link a recognitive element to a destructive and ridding set of effector functions. Any host that allowed the destruction and ridding of the pathogen to entrain a significant measure of destruction and ridding of the host, would obviously self-destruct (i.e., be deleted by evolutionary selection). The self-nonself discrimination is germline encoded for defense mechanisms, but it is somatically learned for the immune system and this is the fundamental difference between the two. When referring to the defense mechanisms of vertebrates, immunologists like to use the term "innate immune systems" to describe the germline encoded class of defense mechanism.

The acquisition of a somatically learned S-NS discrimination during vertebrate evolution permitted the immune system to develop large recognitive repertoires compared to those of defense mechanisms. It is the seemingly boundless size of the immune repertoire that fascinates immunologists.

Recognition without any consequence would be evolutionarily unselectable. This indissoluble linkage is what drives the pathway of decisions that the immune system must make on encountering an antigen.