Contemporary Immunology – serie

The initial impetus to create a work combining aspects of cel- lular immunology with their clinical applications grew from the ed- itors' discussions of the area's needs with many of the leaders in the field over a period of time. From the nucleus of ideas that emerged, we have here attempted to create a unified and inte- grated coverage of the rapidly growing field of cellular immunology research and to trace out-from what seems at times a genuine plethora of important new findings-the many and often impor- tant clinical implications. Because of this approach, the chapters of Clinical Cellular Im- munology attempt to be more than critical reviews of research and clinical data, going beyond analysis to synthesize working hypotheses about the functional meaning of cellular immunological phenomena and their likely clinical significance. To accomplish this undertaking, the text begins first with a consid- eration of the molecular aspects of antigen recognition (Luderer and Harvey) and of the ensuing regulatory program initiation (Fathman).Then, the functional subsets oflymphocytes as they in- teract to produce and control the developing immune response are explored in detail (Sigel et a1.), followed by a unique analytical dis- section of the action of immunosuppressive agents on the sundry inductive and regulatory immunologic pathways (Sigel et al.). A majority of the data and conclusions drawn by the authors in the previous chapters arise from work on murine systems, al- though wherever appropriate, human data has been introduced.

The immune system can deal effectively with the majority of viruses and bacteria, less effectively with parasites, and very poorly with cancer. Why is this so? Why are McFarlane Burnet's and Lewis Thomas' predictions that the immune system is in­ volved in ridding the body of cancer cells, encapsulated in the catchy phrase "immunologic surveillance," so difficult to experi­ mentally establish? Cancer differs from infectious agents in being derived from the host. Hence, it has been postulated that cancer cells lack anti­ gens that the immune system can recognize. They are not "im­ munogenic. " However, this argument is seriously weakened by the existence of numerous human autoimmune diseases, in which the immune system effectively recognizes and attacks a va­ riety of self tissues. Thus, the potential clearly exists for recogni­ tion of the surfaces of tumor cells. Professor Naor and his colleagues have written a book that explores another possible reason: cancer cells are recognized by the immune system-but is it possible that the consequence of recognition is inhibition of the immune system-by suppressor T cells or macrophages? The evolution of the malignant state may only occur in individuals who develop this suppression. This book reviews the evidence that suppressor cells, poorly characterized and difficult to study, may be of fundamental im­ portance in cancer. In fact, our incapacity to understand the na­ ture of suppressor cells and their mode of action is one of the ma­ jor problems in immunology research today.

This cutting-edge review of the current status of research on the early development of lymphocytes emphasizes molecular mechanisms controlling lineage commitment and selection. The reviews explore cellular and molecular aspects of the microenvironment in regulating lymphoid development, discuss ligands and receptors that mediate interactions between progenitor and cells comprising the stromal microenvironment, and demonstrate which are the triggering receptors, signaling pathways, and the developmental checkpoints controlling correct development of B- and T-cells. There is also a comparison of the vital roles of transcription factor combinations in establishing cell identity in the erythroid, myeloid, B, and T lineages. By juxtaposing the insights and approaches normally confined to either immunology or hematology, this important book will help spark the growth of new research initiatives at the intersection of these two fields.

Autoimmune Reactions tackles fundamental questions about how the immune system can destroy invading microbial pathogens without causing damage to itself and other "self" systems. The authoritative experts writing here explore the mechanistic aspects of such autoimmune diseases as lupus, rheumatoid arthritis, diabetes, and autoimmune thyroid disease, and where possible delineate how malfunctioning immunological mechanisms can lead to clinical symptoms. They also discusses possible general mechanisms of autoimmune disease - e.g., molecular mimicry and dysfunctional antigen presentation - and their current limitations as unifying explanations of the diseases described. The book illustrates the type of thinking and research that should eventually permit development of palliatives and cures for autoimmune diseases.

Leading basic and clinical investigators from around the world summarize the most recent research on the molecular and cellular origins of lupus. Their cutting-edge articles review the mechanisms underlying abnormal immunity and introduce the powerful new concept that a disorder of multiple genes underlies the abnormal immune response, leading directly to the development of lupus. This pathophysiology is shown to involve a wide variety of cell types, including T cells, B cells, natural killer cells, macrophages/monocytes, and endothelial cells. Over time, the resulting long-term inflammation causes irreversible cell destruction and, ultimately, organ failure. Lupus: Molecular and Cellular Pathogenesis is a masterful new synthesis of all the new knowledge emerging today about lupus. Its new perspectives will sharpen the focus of research and ultimately lead to better and more effective treatment.

A team of expert investigators and clinical researchers comprehensively review complement's basic biology, its role in disease, methods to measure its activity, and strategies for its inhibition in patients. Each chapter focuses on a specific area of basic and applied complement biology, spelling out the activation pathways and complement receptors. Informative animal models are discussed in detail, including the relative values of each model and the important interspecies differences that can distort the interpretation of preclinical studies. The emphasis throughout is on the pros and cons of the therapeutic use of recombinant complement inhibitors in specific diseases. Cutting-edge and innovative, Therapeutic Interventions in the Complement System highlights for today's researcher and biotechnologist effective strategies of drug discovery and development that are producing valuable new complement inhibitors for the treatment of a wide variety of clinically important diseases.

Caroline Hebert and a panel of key experimentalists and clinical investigators comprehensively review the state-of-the-art in the chemokine field, ranging from the effects of chemokines and their receptors in retroviral infections, to their role in inflammation, angiogenesis/angiostasis, and tumor cell biology. The book examines in detail fifteen recently identified chemokines and elucidates the role of chemokine function in vivo from animal experiments. Animal models are also used to explore how chemokines operate in a variety of chronic and acute inflammatory diseases and in noninflammatory processes. A detailed review of the emerging role of chemokines in viral biology is also presented, with emphasis on HIV biology and novel therapeutic possibilities. Chemokines in Disease: Biology and Clinical Research summarizes the rapidly expanding knowledge of a dazzling array of chemokines and provides fresh insights into the development of powerful new drugs for treating a wide spectrum of diseases.

The initial impetus to create a work combining aspects of cel- lular immunology with their clinical applications grew from the ed- itors' discussions of the area's needs with many of the leaders in the field over a period of time. From the nucleus of ideas that emerged, we have here attempted to create a unified and inte- grated coverage of the rapidly growing field of cellular immunology research and to trace out-from what seems at times a genuine plethora of important new findings-the many and often impor- tant clinical implications. Because of this approach, the chapters of Clinical Cellular Im- munology attempt to be more than critical reviews of research and clinical data, going beyond analysis to synthesize working hypotheses about the functional meaning of cellular immunological phenomena and their likely clinical significance. To accomplish this undertaking, the text begins first with a consid- eration of the molecular aspects of antigen recognition (Luderer and Harvey) and of the ensuing regulatory program initiation (Fathman).Then, the functional subsets oflymphocytes as they in- teract to produce and control the developing immune response are explored in detail (Sigel et a1.), followed by a unique analytical dis- section of the action of immunosuppressive agents on the sundry inductive and regulatory immunologic pathways (Sigel et al.). A majority of the data and conclusions drawn by the authors in the previous chapters arise from work on murine systems, al- though wherever appropriate, human data has been introduced.

The authoritative experts writing here explore the mechanistic aspects of such autoimmune diseases as lupus, rheumatoid arthritis, diabetes, and autoimmune thyroid disease, and where possible delineate how malfunctioning immunological mechanisms can lead to clinical symptoms.

The immune system can deal effectively with the majority of viruses and bacteria, less effectively with parasites, and very poorly with cancer. Why is this so? Why are McFarlane Burnet's and Lewis Thomas' predictions that the immune system is in­ volved in ridding the body of cancer cells, encapsulated in the catchy phrase "immunologic surveillance," so difficult to experi­ mentally establish? Cancer differs from infectious agents in being derived from the host. Hence, it has been postulated that cancer cells lack anti­ gens that the immune system can recognize. They are not "im­ munogenic. " However, this argument is seriously weakened by the existence of numerous human autoimmune diseases, in which the immune system effectively recognizes and attacks a va­ riety of self tissues. Thus, the potential clearly exists for recogni­ tion of the surfaces of tumor cells. Professor Naor and his colleagues have written a book that explores another possible reason: cancer cells are recognized by the immune system-but is it possible that the consequence of recognition is inhibition of the immune system-by suppressor T cells or macrophages? The evolution of the malignant state may only occur in individuals who develop this suppression. This book reviews the evidence that suppressor cells, poorly characterized and difficult to study, may be of fundamental im­ portance in cancer. In fact, our incapacity to understand the na­ ture of suppressor cells and their mode of action is one of the ma­ jor problems in immunology research today.

A team of expert investigators and clinical researchers comprehensively review complement's basic biology, its role in disease, methods to measure its activity, and strategies for its inhibition in patients. Each chapter focuses on a specific area of basic and applied complement biology, spelling out the activation pathways and complement receptors. Informative animal models are discussed in detail, including the relative values of each model and the important interspecies differences that can distort the interpretation of preclinical studies. The emphasis throughout is on the pros and cons of the therapeutic use of recombinant complement inhibitors in specific diseases. Cutting-edge and innovative, Therapeutic Interventions in the Complement System highlights for today's researcher and biotechnologist effective strategies of drug discovery and development that are producing valuable new complement inhibitors for the treatment of a wide variety of clinically important diseases.

Caroline Hébert and a panel of key experimentalists and clinical investigators comprehensively review the state-of-the-art in the chemokine field, ranging from the effects of chemokines and their receptors in retroviral infections, to their role in inflammation, angiogenesis/angiostasis, and tumor cell biology. The book examines in detail fifteen recently identified chemokines and elucidates the role of chemokine function in vivo from animal experiments. Animal models are also used to explore how chemokines operate in a variety of chronic and acute inflammatory diseases and in noninflammatory processes. A detailed review of the emerging role of chemokines in viral biology is also presented, with emphasis on HIV biology and novel therapeutic possibilities. Chemokines in Disease: Biology and Clinical Research summarizes the rapidly expanding knowledge of a dazzling array of chemokines and provides fresh insights into the development of powerful new drugs for treating a wide spectrum of diseases.

Leading basic and clinical investigators from around the world summarize the most recent research on the molecular and cellular origins of lupus. Their cutting-edge articles review the mechanisms underlying abnormal immunity and introduce the powerful new concept that a disorder of multiple genes underlies the abnormal immune response, leading directly to the development of lupus. This pathophysiology is shown to involve a wide variety of cell types, including T cells, B cells, natural killer cells, macrophages/monocytes, and endothelial cells. Over time, the resulting long-term inflammation causes irreversible cell destruction and, ultimately, organ failure. Lupus: Molecular and Cellular Pathogenesis is a masterful new synthesis of all the new knowledge emerging today about lupus. Its new perspectives will sharpen the focus of research and ultimately lead to better and more effective treatment.

Carrying on the high standards of the much praised first edition (Durum and Muegge, Cytokine Knockouts, 1998), Giamila Fantuzzi and a panel of experts have generated completely new chapters to reflect the use of many novel mouse strains and the hundreds of recent studies on cytokine physiology.

A critical review of the classic, as wells as most recent-and quite seminal-findings concerning the phenotypic and molecular characteristics of both fetal and neonatal B and T cells, the cells that mediate antibody and cellular immune responses in newborns and infants. Dr. Bona shows how the antibody response of neonates is modulated by maternal antibodies and how, in certain cases, this can cause transient or life-threatening neonatal autoimmune disease. He also describes the characteristics of neonatal tolerance induced by foreign allo- and self-antigens, which are the basis for understanding impaired infant immune response and which provide a rationale for the development of efficient neonatal vaccines. By making clear the characteristics and differences between the immune system and the immune responses of both newborns and infants, compared to those of adults, Dr. Bona offers insights and challenging hypotheses that promise to help overcome the poor responses of neonates to various antigens.

Discovery of the BLyS (also known as BAFF) family of ligands and receptors has yielded a paradigm shift in our view of B-lymphocyte selection, survival, activation, and homeostasis. Previously, the B-cell antigen receptor (BCR) was viewed as the sole mediator of these parameters, in which BCR signals were not only dominant but were also linearly related to consequent outcomes. However, appreciating that BLyS signaling is an equal partner in establishing and maintaining B-cell pools in- cated that additional regulatory complexity – apparently based on population density and homeostatic demands – had to be included in models of B-cell behavior. This mounting interest was ampli?ed by evidence of a clear relationship to autoim- nity. The resulting ?urry of research activity has yielded a wealth of information and insights, impacting basic concepts in B-cell tolerance and activation as well as revealing novel translational strategies for autoimmunity, neoplasia, and transplant tolerance. This book includes 12 chapters that together yield an overview of these advances and ideas. The initial excitement generated by associations with humoral autoimmunity, coupled with profound B lineage phenotypes in knockout mouse models, prompted immediate questions: What do these receptors and cytokines look like, how do they interact, what cells express them, and how does this inform our understating of their biology? Indeed, probing the structural features of BLyS family ligands and rec- tors has afforded substantial insight, as have studies directed toward understanding the basic biological actions of these molecules.

Despite the tremendous diversity of the cells of the hematopoietic system, they are all derived from common precursor cells that are generated in the fetus and persist into adult life. In this regard, Band T lymphocytes, which comprise the two arms of the antigen-specific and inducible immune system, though functionally very different, are descendants of the same stem cell precursor. In the past several years, we have witnessed an explosion of information regarding the process by which differentiation of B-and T-cells from stem cells occurs. This information, like the answers to most important biological questions, has come from multiple and diverse directions. Because all hematopoietic cells arise from common precursors, complex regulatory processes must be involved in determining commitment to various lineages. Understanding commitment to the B- or T-cell lineage remains incomplete; however, identification of transcription factors necessary for progression along specific B-and T-cell pathways suggests that we are on the verge of understanding the molecules involved in the initial fate-determining steps. Studies of this type previously could be accomplished only in nonmammalian systems that are more amenable to genetic approaches. However, new technologies allow increasingly elegant and informative studies in mammalian systems, particularly for cells of the hematopoietic system.

Carrying on the high standards of the much praised first edition (Durum and Muegge, Cytokine Knockouts, 1998), Giamila Fantuzzi and a panel of experts have generated completely new chapters to reflect the use of many novel mouse strains and the hundreds of recent studies on cytokine physiology. Comprehensive reviews of the numerous often-surprising results obtained using cytokine knockout mice are provided, along with much important information about cytokine biology and physiology. For those not familiar with cytokine research, the authors present a critical discussion of the advantages and disadvantages of using cytokine knockout mice in various fields of research.

A critical review of the classic, as wells as most recent-and quite seminal-findings concerning the phenotypic and molecular characteristics of both fetal and neonatal B and T cells, the cells that mediate antibody and cellular immune responses in newborns and infants. Dr. Bona shows how the antibody response of neonates is modulated by maternal antibodies and how, in certain cases, this can cause transient or life-threatening neonatal autoimmune disease. He also describes the characteristics of neonatal tolerance induced by foreign allo- and self-antigens, which are the basis for understanding impaired infant immune response and which provide a rationale for the development of efficient neonatal vaccines. By making clear the characteristics and differences between the immune system and the immune responses of both newborns and infants, compared to those of adults, Dr. Bona offers insights and challenging hypotheses that promise to help overcome the poor responses of neonates to various antigens.