The quantal theory of immunity

Kendall A Smith

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Cell Research (2006)16: 11-19 2006 IBCB, SIBS, CAS All rights reserved 1001-0602/06 $ 30.00

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REVIEW

www.nature.com/cr

The quantal theory of immunity

Kendall A Smith1

1The Division of Immunology, Department of Medicine, Weill Medical College, Cornell University, New York, NY 10021, USA

Exactly how the immune system discriminates between all environmental antigens to which it reacts vs. all self-antigens to which it does not, is a principal unanswered question in immunology. As set forth in this review, because of the advances in our understanding of the immune system that have occurred in the last 50 years, for the rst time it is possible to formulate a new theory, termed the Quantal Theory of Immunity, which reduces the problem from the immune system as a whole, to the individual cells comprising the system, and nally to a molecular explanation as to how the system behaves as it does.

Cell Research (2006) 16:11-19. doi:10.1038/sj.cr.7310003; published online 16 January 2006

Keywords: self:nonself recognition, immune system, interleukin-2 (IL2), T cell antigen receptor (TCR), quantal (all-or-none), macromolecular complex

Introduction

Almost fty years ago Sir MacFarlane Burnet proposed the Clonal Selection Theory to explain how the immune system functions [1]. Prior to Burnets theory, Neils Jerne had proposed a natural selection theory in attempt to explain antibody formation [2], and Burnets contribution was in part an extension of the concept of antigen determination of immunity. However, Burnet improved upon Jernes idea by giving the immune system a cellular basis, proposing that an individual cell is the source of each unique antibody. In addition, Burnet introduced the idea of clonal expansion through proliferation to explain how the immune system can mobilize a huge number of antigen reactive cells from very few antigen-reactive precursors. He also proposed that lymphocytes were the main cells making up the immune system, thereby correcting Jernes fallacious hypothesis that phagocytic cells ingest antigen-antibody complexes, and then use the ingested antibodies as templates for the formation of additional antibody molecules.

Now, 50 years later it is amazing that Burnets Clonal

Selection Theory has been experimentally tested, has held up and now is established as fact, so that it is now accepted as one of the natural Laws of biology. Moreover, in the past...