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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.
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