Theoretical Immunology, Part One PDF

Foreword

Immunology is one of the most exciting branches of biology. Advances are being made almost daily in a broad range of experimental areas. The current notariety of AIDS has made us all keenly aware, even in this age of modern medicine and miracle drugs, of the absolute necessity of a functioning immune system. Our inability to cure HIV infection or even to design therapies that eliminate its symptoms points out our lack of detailed understanding about the operation of the immune system.

The immune system is complex system of cells and molecules distributed throughout our bodies. Analogies have been drawn between the immune system and the nervous sytstem. Like the nervous system, the immune system performs pattern recognition tasks, learns and retains a memory of the antigens that it has fought. Many of the "players" in the immune system, the specific cells and molecules whose coordinate activity produce the phenomena of immunology, have been identified. The interactions between these cells and molecules are slowly being elucidated. The mechanisms that actually regulate the immune system are by and large still unknown.

Unlike many areas of biology, theoretical ideas have played a major role in the development of the field. Controversies such as instructive vs. selective theories of antibody formation, germ-line vs. somatic mutation models for the generation of antibody diversity, and regulatory circuits vs. idiotypic networks have dominated both the intellectual development of the field and determined the direction of much experimental effort. Quantitative theories, while playing a role in the design and interpretation of various assay systems (e.g., complement fixation, the precipitin reaction, the hemolytic plaque assay) have to date not been significant in the intellectual development of the field. This may be changing as the field addresses more quantitative issues such as the role of somatic hypermutation in the generation of antibody diversity, the role of receptor clusters in cell stimulation and desensitization, the effects of competition between solution phase antibodies and cell surface receptors of the same specificity for binding various ligands including anti-idiotypic antibodies, the effects of different concentrations of growth factors and of changes in receptor affinity and receptor number on cell stimulation, cell proliferation and cell differentiation, etc. Quantitative theories will also be essential for the development of global models of the immune system in which both the spatial and temporal aspects of humoral and cell-mediated responses are integrated into a single model, and may well be needed in order to understand the role of idiotypic networks in immune regulation. 

Author: Alan S. Perelson