Lymphocyte Activation

The Janeway's Immunobiology CD-ROM, Immunobiology Interactive, is included with each book, and can be purchased separately. It contains animations and videos with voiceover narration, as well as the figures from the text for presentation purposes.

The ac ti vati on of Iymphocytes by physiologie ligands has become a central area of study for immunologists. Furthermore, Iymphocytes offer many advantages for the study of general aspects of receptor-mediated cellular activation. For these reasons, research on the cellular and molecular aspects of the activation of Iymphocytes by antigens, antigen analogues, Iymphokines and other growth factors has expanded enormously in the last several years. Aseries of conferences, "The International Conferences on Lymphocyte Activation", has been initiated to meet the growing need for a forum for the discussion of the topics that are included within the area of Iymphocyte activation. This volume represents the proceedings of the Second International Conference on Lymphocyte Activation and Immune Regulation, held on February 18-20, 1988 at Newport Beach, California. The proceedings comprise four major sections. The first deals with the T cell receptors and T cell activation. It includes a model for the T cell receptor interaction with a complex of MHC plus antigen, structure of y c'i T cell receptor and their distinct isotypic forms, the role of zeta chain in the expression and structure of T cell receptors and its role in transmembrane signalling. The use of somatic cell mutants in the study of signal transduction function of the T cell antigen receptors and the early and late steps of signal transduction via a / ß T cell antigen receptors are discussed.

Recent advances in the understanding of the major events that shape the immune recog nition system have been remarkable. The analysis of immunoglobulin (Ig) gene organization and Ig repertoire diversification in lower vertebrates has provided new insight into this process in mammals. Similarly, the understanding of the early development of lymphocytes and of the acquisition of immunological tolerance has been aided by elegant studies in quail/chicken chimeras, using the power of the distinctive markers of the constitutive cells of these birds. Great strides have been made in understanding the role played by major histocompatibility complex (MHC) molecules in antigen presentation and in repertoire selec tion within the thymus. The use of transgenic mice expressing specific T-cell receptor (TCR) genes has elucidated the process of both positive and negative selection. In parallel, there has been considerable progress in our understanding of tolerance, based in part on the use of markers for the V fJ genes of T-cell receptors and in part on the analysis of the behavior of long term T-cell lines. This has led to the realization that both clonal deletion and clonal anergy may play critical roles in the maintenance of unresponsiveness to self antigen. Molecular analysis of the requirements for expression of membrane immunoglobulin molecules has revealed the existence of a complex that appears to be of critical importance in mediating signalling through Ig receptors. In addition, major insights have been obtained into the regulation of expression of genes of immunologic interest.

T cells play a vital role mediating adaptive immunity, a specific acquired resistance to an infectious agent produced by the introduction of an antigen. There are a variety of T cell types with different functions. They are called T cells, because they are derived from the thymus gland. This volume discusses how T cells are regulated through the operation of signaling mechanisms. Topics covered include positive and negative selection, early events in T cell receptor engagement, and various T cell subsets.

During the past 5 years rapid progress has been made in the understanding of biochemical pathways for signal transduction in lymphocyte activation. Gene cloning technology has been instrumental in defining and making available in pure form of a number of growth and differentiation factors, in the characterization of their receptors, and in the delineation of genes for the T cell receptor. This book is divided into 6 sections. Section 1 deals with the molecular structure of the T cell receptor. Section 2 discusses the role of the T cell receptor, membrane ion channels and biochemical pathways of signal transduction in T cell activation. The molecular structures and biological and immunological effects of interleukin 1, interleukin 2 and interleukin 3 are presented in Section 3. This section also details the structure of interleukin 2 receptor and its use as a target for therapy for certain leukemias. Section 4 includes the biochemical events which occur following the delivery of the signal for B cell activation, proliferation, and differentiation by antigen, growth/differentiation factors. The molecular structure of B cell stimulating factors is also discussed. The role of oncogene expression in cellular activation and differentiation is included in Section 5. The cellular and molecular basis of natural killing and the molecular basis of cyc1osporin A-mediated immunosuppression are discussed in detail in Section 6. We hope this book will serve as a reference work on basic mechanisms of lymphocyte activation, proliferation, and differentiation for immunologists and molecular biologists.

In recent years rapid progress has been made in the areas of T cell and B cell biology, cell-cell and cell-matrix/stroma interactions. The use of isolated subunits of the T cell receptor invariant chains has been instrumental in defining their role in signal transduction and tyrosine phosphorylation. A role of src family phosphotyrosine kinases in T cell activation has been demonstrated and several phosphotyrosine kinase substrates have been identified and their functions characterized. Homologous recombinant techniques have led to the development of murine strains that lack CD4 or CD8 expression. These models are likely to be instrumental in studying the role of T cell subsets in autoimmune disorders, tissue transplant rejection and tumor rejection. A role of major histocompatibility complex I in the development of T cell subsets and NK cells has been defined. Recent data suggest a role of interaction between plasma membrane molecules of activated T helper cells and B cells, B cells primed with plasma membrane of activated T helper cells and cytokines, and interaction between bone marrow stromal cells and B cell progenitors and precursors, in the B cell development, proliferation, and differentiation. The structure and functions of adhesion molecules, especially with regard to signal transduction and homing events, are better defined.