Regulation Of Immune Gene Expression

This book encompasses the proceedings of a conference held at Trinity College, Oxford on September 21-25, 1985 organized by a committee comprised of Drs. M. Crumpton, M. Feldmann, A. McMichael, and E. Simpson, and advised by many friends and colleagues. The immune response gene workshops that took place were based on the need to understand why certain experimental animal strains were high responders and others were low responders. It was assumed that identification of the immune response (Ir) genes and definition of their products would explain high and low responder status. Research in the ensuing years has identified the Ir gene products involved in antibody responses as the la antigens, or MHC Class II antigens. These proteins are now well defined as members of the immunoglobulin gene superfamily, and their domain structure is known. Epitopes have been defined by multiple mono clonal antibodies and regions of hypervariability identified. Their genes have been identified and cloned. The basic observation of high and low responsive ness to antigen is still not understood in mechanistic terms, however, at either the cellular or molecular level. This is because the rate of progress in immune regulation has been far slower than in the molecular biology of the MHC Class II antigens. This is not surprising, since immune regulation is a very complex field at the crossroads of many disciplines.

This book explores the major cytokines, such as IL-1 and IFN-γ, with respect to the regulation of their gene expression and protein production in specific immune cell types. It discusses both healthy physiological settings and in pathological situations in which the expression of some cytokines could be dysregulated, resulting in either immunodeficiency or exacerbated inflammatory sequelae in animal models as well as in human patients. Cytokines are important regulators of immune responses that require the highly coordinated participation and communication of multiple cell types. The expression of cytokines by various producer cell types is therefore carefully regulated in response to environmental cues at multiple levels: transcription, translation and posttranslational modification. Presenting cutting-edge advances in our understanding of the regulation of cytokine expression, this book is a valuable resource for anyone involved or interested in immune regulation.

This book explores existing and potential strategies for using the genome sequences of human, mouse, other vertebrates and human pathogens to solve key problems in the treatment of immunological diseases and chronic infections. The assembled genome sequences now provide important opportunities for solving these problems, but a major bottleneck is the identification of key sequences and circuits controlling the relevant immune reactions. This will require innovative, interdisciplinary and collaborative strategies of a scale and complexity we are only now beginning to comprehend. Specific problems addressed include the following: What kinds of information are we lacking to understand how the genome sequence specifies the differentiation and response of immune system cells, and system behaviour such as immunological memory and tolerance? Which genome sequences and cellular circuits cause or prevent pathological immune responses to foreign pathogens, allergens or self-tissues? Which host and pathogen genome sequences and cellular circuits explain the failure of sterilizing immune responses to sophisticated human pathogens such as the agents of tuberculosis, malaria, metazoan parasites and chronic viruses? Containing contributions from a range of leading experts in the field, this book provides an important new perspective for clinical immunologists and basic researchers alike.

Provides a dialogue on the nature of the membrane signals and intracytoplasmic events that provoke immunity. The debate ranges over biochemistry, physiology, molecular genetics, as well as classical cellular immunology. Input came from over 70 of the world's leading investigators.