On occasion, the innate immune system is referred to as the "primitive" immune system. Perhaps this has dissuaded immu nologists from analyzing it as energetically as they have analyzed the adaptive immune system during the past two decades. But while its phylogenetic origins are indeed ancient, and though it is "of the first type", there is nothing crude, nothing unsophisti cated, and nothing "inferior" about innate immunity. On the contrary, the innate immune system has had time to achieve a level of refinement that is nothing short of dazzling, and a modicum of respect is at long last due. Any immune system has two cardinal functions. It must destroy a broad range of pathogens, and it must spare the host. The adaptive immune system has applied a modular solution to these problems. Each cell of the adaptive immune system is prescreened to eliminate those that would produce untoward interactions with self; each cell is pre-programmed to recognize a foreign epitope that the host might one day encounter. Hence, the duties of each individual lymphocyte are quite circumscribed.

This monograph deals with the impact of classical genetics in immunology, prov- ing examples of how large immunological questions were solved, and new fields opened to analysis through the study of phenotypes, either spontaneous or induced. As broad as biology has become, there are those who do not fully understand what the genetic approach is, and how it differs fundamentally from most of the methods available to natural scientists. They may hold the opinion that genetics has run its course since Mendel read his paper on peas in 1865. "Why bother with classical genetics," they may ask. "Won't all genes be knocked out soon anyway?" Or they are intimidated by genetics, with its heavy reliance on model organisms that seem so alien. "What has C. elegans to do with me?" the questioning might go. "It doesn't even have lymphocytes. " Such skeptics may be unaware that the mouse is fast becoming as tractable a model organism as the fly, and that humans may not be too far behind. So I would like to introduce the topic with a few words about the power of genetics, and why it has contributed so much to immunology, and to bi- ogy in general. Genetics, as the word is used here, is not merely the science of heredity, but much more than that. It is the science of exceptions: the science that takes note of heritable variation and seeks to explain it at the most fundamental level.