The First International Workshop on Mechanisms in Cell-Mediated Cytoxicity was held at Carry-Ie-Rouet, France, September 14-16, 1981. The Workshop brought together for the first time leading investiga tors in each of the principal areas of cell-mediated cytotoxicity, as well as experts in the area of complement-mediated cytoxicity. Formal research presentations were held to a minimum, the emphasis being on open discussion of current knowledge about mechanisms of cytoxicity in each of the systems under consideration. The major objectives of the Workshop were 1) to compare and integrate what is known about the mechanism(s) of cytoxicity in each system; 2) to determine whether, on the basis of information in hand, it seems likely that the mechanisms of cytotoxicity in the various systems are the same or are unique; and 3) to stimulate thinking about new approaches to elucidating the fundamental mechanisms by which certain cells are able to kill other cells.

This book is derived from contributions to the Second International Workshop on Mechanisms in Cell-Mediated Cytotoxicity, held in Annopolis, Maryland, June 10-13, 1984. This workshop was organized by an international committee of immunologists interested in lymphocyte cytotoxic mechanisms (G. Berke, W.R. Clark, P. Golstein, M. Hanna, P. Henkart, R. Herberman, H.R. MacDonald, E. Martz, and C. Nathan), who strove to invite participants who have made major contributions to this field. The Workshop was a follow-up to the highly successful 1981 Workshop, whose proceedings Workshop were published by Plenum as Mechanisms in Cell-Mediated Cytotoxicity, edited by W.R. Clark and P. Golstein. That volume has been much appreciated by researchers and students since it contains accounts of most of the current approaches to understanding cytotoxic lymphocyte mechanisms all in one volume. The present book may be viewed as a follow-up to the first one, and in our opinion fairly summarizes the varying current viewpoints on lymphocyte cytotoxic mechanism. It should be noted that the discussions have been transcribed directly by us, and the participants have not had an opportunity to edit their remarks. We have tried to maintain some of the style of the actual discussion in these transcripts. In some cases technical problems prevented usable transcriptions from being made, and hence not all of the actual discussion at the workshop is reproduced here.

This book is derived from contributions to the Second International Workshop on Mechanisms in Cell-Mediated Cytotoxicity, held in Annopolis, Maryland, June 10-13, 1984. This workshop was organized by an international committee of immunologists interested in lymphocyte cytotoxic mechanisms (G. Berke, W.R. Clark, P. Golstein, M. Hanna, P. Henkart, R. Herberman, H.R. MacDonald, E. Martz, and C. Nathan), who strove to invite participants who have made major contributions to this field. The Workshop was a follow-up to the highly successful 1981 Workshop, whose proceedings Workshop were published by Plenum as Mechanisms in Cell-Mediated Cytotoxicity, edited by W.R. Clark and P. Golstein. That volume has been much appreciated by researchers and students since it contains accounts of most of the current approaches to understanding cytotoxic lymphocyte mechanisms all in one volume. The present book may be viewed as a follow-up to the first one, and in our opinion fairly summarizes the varying current viewpoints on lymphocyte cytotoxic mechanism. It should be noted that the discussions have been transcribed directly by us, and the participants have not had an opportunity to edit their remarks. We have tried to maintain some of the style of the actual discussion in these transcripts. In some cases technical problems prevented usable transcriptions from being made, and hence not all of the actual discussion at the workshop is reproduced here.

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.

This volume synthesizes recent groundbreaking advances in our knowledge of the molecular mechanisms, biological roles, and medical applications of cytotoxic lymphocytes. Leading investigators examine current concepts on the recognition of antigen by T-cell receptors; the molecules mediating target recognition by natural killer cells; the intracellular signalling cascades triggered by these molecules; and the effector molecules that damage target cells. The contributors present new insights into the roles of cytotoxic lymphocytes in vivo in immune regulation, autoimmunity, antiviral resistance, and tumor surveillance. Several chapters explore potential medical applications of cytotoxic lymphocytes, including vaccines, tumor therapy, and treatment of HIV infection.

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Our motivation for putting together this book was the need for a single source reference that could be used as an introduction to cell-mediated cytotoxicity for newcomers to this field, such as students and fellows beginning work in our laboratories. At present no such book is available, and we felt that it would be useful as a teaching tool and as a way of conveying our enthusiasm about recent progress in the cytotoxicity field to our colleagues in allied areas. It was with some hesitation that we approached our colleagues with the proposal for this book, and we were pleased to find them very supportive of the idea and willing to participate. We thought it important to broaden the scope of the book to include historical, molecular, cell biological, and clinical aspects of cell-mediated cytotoxicity. To our knowledge this is the first book on cell-mediated cytotoxicity with such a broad scope. Historically, studies on cellular cytotoxicity were part of cellular immunology from its origin. One development of tremendous import was the advent of the 51 Cr assay, which allowed this arm of the immune response to be measured easily and quantitatively. Thus, a readout of this effector pathway is available within a few hours; other immune effector functions can take days or even longer to assay, and the assays are often less quantitative.

Since programmed cell death was first described in insects in 1964 and apoptosis was described in 1972, rapid progress has been made in understanding the basic mechanisms and genes regulating programmed cell death and apoptosis. In addition, defects in various genes regulating programmed cell death have been delineated in several experimental models of human diseases. This volume surveys various aspects of these rapidly developing areas of research in programmed cell death/apoptosis. This volume should be of interest to basic immunologists and molecular biologists. The volume begins with a historical perspective of cell death. The remainder of the volume is divided into four different parts. Part I deals with the signaling pathways in apoptosis, including cell cycle control of apoptosis, role of ceramide in apoptosis, role of antibody signaling, and biochemical regulation of apoptosis. The mechanisms for recognition of apoptotic lymphocytes by macrophages are also reviewed. Part II examines the role of various genes that regulate apoptosis, including the role ofFas, FasL, and other TNF family members in apoptosis and homeostatic regulation of immune response. Recently described splice variants and their influence on apoptosis are also reviewed, and the role of the members of the Bcl-2 family in apoptosis is discussed in detail. Part III reviews various aspects of apoptosis in B lymphocytes, including mechanisms that regulate apoptosis/survival of B lymphocytes and the regulation of Fas-mediated apoptosis in B lymphocytes.