by Kendall A Smith (Cornell University, USA)

This book explains how the immune system functions, namely, how individual cells of the immune system make the decision to respond or not to respond to foreign microbes and molecules, and how the critical molecules function to trigger the cellular reactions in an all-or-none (quantal) manner. To date, there has not been a complete description of the immune system and its cells and molecules, primarily because most of the information has accumulated only in the last 40 years and our understanding has been expanding rapidly only in the last 20 years. It is now clear that the cells have evolved a way to “count” the number of foreign antigenic molecular “hits”, and they only react when a critical number of events have accumulated. Subsequently, control over the reaction is transferred to a systemic lymphocytotrophic hormone system that determines the tempo, magnitude and duration of the immune reaction.

This book explains in detail how the immune system, cells and molecules work for the first time. With this understanding as a basis, the pathogenesis of autoimmunity can now be understood as a mutational usurpation of the genes encoding molecules that participate in a sensitive feedback regulatory control of the immune reaction. By comparison, malignant transformation is understood as a mutational usurpation of the genes encoding the molecules that control the quantal decision to proliferate, so that normal ligand/receptor cell growth control is circumvented. This molecular understanding of the immune system is especially important for the design of successful vaccines, and also explains why vaccines fail.

• Introduction: The Evolution of Our Understanding of the Immune System
• Molecular Immunology
• The Problem: Understanding How Molecules Direct the Behavior of Cells Compromising the Immune System
• The Quantal Theory of Immunity
• The VariabILity of Cell Cycle Progression and the Competence and Progression Phases of the Cell Cycle
• The Quantal Nature of IL-2-Promoted T Cell Cycle Progression
• The Molecular Basis for Quantal IL-2/IL-2R Signaling of Cell Cycle Progression: The IL-2/Receptor Interaction
• The Molecular Basis for Quantal IL-2/IL-2R Signaling of Cell Cycle Progression: IL-2 and IL-2 Receptor Metabolism
• The Molecular Basis for Quantal IL-2/IL-2R Signaling of Cell Cycle Progression: IL-2 Receptor Signaling via the JAK/STAT Pathway
• The Molecular Basis for Quantal IL-2/IL-2R Signaling of Cell Cycle Progression: IL-2 Receptor Signaling via Phosphorylation of IL-2R β Chain Y338
• The T Cell Antigen Receptor Complex and the Quantal Regulation of the IL-2 and IL-2R Genes
• Signaling via the T Cell Antigen Receptor Complex
• Negative Feedback Regulation of T Cell Antigen Receptor Complex Signaling: Attenuation of IL-2 Gene Expression