The topic of biological response modifiers has attracted the attention of many biomedical investigators, including immunologists, oncologists, pharmacologists, microbiologists, and biochemists, as well as clinical practitioners of medicine. This has occurred mainly because of the realization that the complex system of cellular and humoral interactions culminating in a productive immune response is under exquisite regulatory control for normal immune responses and that loss of control may markedly influence the capability of a host to respond in a productive manner to the numerous immunologic "insults" encountered in the environment. Furthermore, biological response modification is considered by many to be a natural offshoot of the relatively new application of "immunotherapy" to cancer. It is widely recognized that "immunotherapy" was practiced at the end of the last century and the beginning of this century when it was recognized that microbial infections were caused by distinct species of bacteria and that passive administration of serum con taining antibody to these microbes or their products could, in many cases, favorably influence the outcome of an infectious process."

Apoptosis is a fascinating concept for the basic scientist. This is not only because of the multifaceted variety of proposed and discovered mechanisms, but because apoptosis represents a fundamental pathway for cell renewal. The study of apoptosis has resulted in an array of discoveries on signal transduc tion and downstream effects that have facilitated and advanced many fields in biology, including research on cancer and other diseases. Thus, the apoptotic process can be viewed as the largest effort of the scientific community to understand how cells work and tissues assemble or remodel. The most direct consequence of this accumulated knowledge is a greater understanding of disease and pathological mechanisms. The end result of these efforts will be significant contributions to health and the adoption of new, never anticipated, therapeutic approaches. This book represents the summation of considerable effort from a significant group of contributors from all over the world as well as from its editors. In this fashion, many viewpoints have been collected and SUbjected to thorough academic discussion. The concepts contained in this medically important volume will stimulate and renew the ideas of scientists and indeed, will generate additional work to advance biological knowledge even further. The emphasis of this volume cements what has been established, adds what has not been explored fully, and creates a fertile ground for further hypotheses that will lead to a more complete understanding of the apoptotic process."

The human immune system, despite having its own sophisticated defence mecha nisms, is inferior to bacteria and viruses with respect to adaptability. Furthermore, our immune system is increasingly exposed to detrimental effects, that is immuno suppressive environmental consequences, unhealthy living, and chronic illnesses. Excessive chemotherapy threatens our immune system even further. This situation demands compensatory prophylactic therapeutic regimes. One of these - specific immunostimulation - is more difficult to achieve than the immunosuppression cur rently used in transplantation surgery and the medical treatment of autoimmune dis eases. The earliest attempts to develop suitable medication for immunostimulation were based on traditional remedies which embodied the accumulated experience of several centuries. Medicinal plants are already being used prophylactically as stan dardized and efficacy-optimized preparations for the treatment of various recur rent infections, or in combination with chemotherapeutics in standard medical practice. In order to rationally apply immunostimulants of plant origin, however, it is necessary to search for the active principles of these substances and to produce them in a pure form. Because suitable screening methods have become available only recently, research in this field is in its very beginning. Further progress can be expected from systematic basic research on the mechanisms underlying immunomodulation. This also applies to verification of clinical efficacy, which is a prerequisite for the acceptance of medications with purported immunostimulatory properties."

It has been clear for a long time that after transplantation of a lymphoid organ, hematopoietic stem cells can regenerate the compartments of the organ, provided that the rest of its architecture - the strome, the epithelia and the vessels - is intact. Ahead lies the even greater challenge to assemble also these other architectural elements of a lymphoid organ by transplanting stem cells. The workshop on lymphoid organogenesis was convened to review current knowledge of and experimental skills involved in this grand project to build a lymphoid organ from its individual cellular components.

''An exciting glance at key issues in contemporary hematopoiesis.'' -The Quarterly Review of Biology

Seventeen years after its initial description, nuclear factor-KB (NF-KB) endures as one of the most studied transcription factors. NF-KB has attracted widespread interest based on the variety of stimuli that activate it, the diverse genes and bio logical responses that it controls, the striking evolutionary conservation of struc ture and function among species, and its involvement in a variety of human diseases. The biochemical basis by which several stimuli converge to activate NF-KB has been largely elucidated during recent years. While first discovered as a key regulatory factor of the immune system, NF-KB is now recognized as an important player in the functioning of many organs and cell types. The ongoing examination of NF-KB signaling has revealed its ever expanding role in immune and inflammatory responses, but also in cancer and development. For this reason, numerous efforts are underway to develop safe inhibitors of NF-KB to be used in the treatment of both chronic and acute disease situations. The present book is the first to review and synthesize our knowledge of this interesting transcription factor. As such, the choice of subjects to review was daunting. To set the stage, an introductory chapter on activators and target genes, as well as the role they play in several responses, has been included."

Based on the assumption that invertebrates as well as vertebrates possess factors regulating hematopoiesis, response to infection or wounding, studies dealing with the evolution of immunity have focused on the isolation and characterization of putative cytokine-related molecules from invertebrates. Until recently, most of our knowledge of cytokine- and cytokine receptor-like molecules in invertebrates has relied on functional assays and similarities at the physicochemical level. As such, a phylogenetic relationship between invertebrate cytokine-like molecules and invertebrate counterparts could not be convincingly demonstrated.
In the present book, recent studies demonstrating cytokine-like activities and related signaling pathways in invertebrates are critically reviewed, focusing on findings from molecular biology and taking advantage of the completion of the genome from the fly Drosophila and the worm Caenorhabditis elegans.

Until recently the only biomedical use of erythrocytes was in transfusion medicine to restore a normal oxygen delivery. The development of a technology that permits one to open and reseal erythrocytes has dramatically changed this perspective. Currently, a number of teams have shown that engineered erythrocytes can behave as circulating bioreactors for the degradation of toxic metabolites or the inactivation of xenobiotics, as drug delivery systems, as carriers of antigens of vaccinal interest, and in many others biomedical applications. The technology of opening and resealing the erythrocytes has also been used successfully to investigate several basic aspects of erythrocyte metabolism, survival, pathology, etc. Thus, researchers in this field have an extraordinary opportunity to specifically modify the erythrocytes by the introduction of enzymes that generate new metabolic abilities, antibodies that inactivate single metabolic steps, or metabolites that can influence oxygen delivery and/or other cell properties. Furthermore, the pharmacokinetics of any drug can be potentially manipulated by using the erythrocytes as a delivery system. This book, The Use of Resealed Erythrocytes, is based on the fourth meeting of the "International Society for the Use of Resealed Erythrocytes as Carriers and Bioreactors" (I. S. U. R. E. ), held in Urbino, Italy, in 1991, and examines the most recent applications and developments of this technology.

For years, toxoplasmosis has been known as disease mostly affecting newborns. Since immunocompromised patients (AIDS) present a high risk of reactivation of chronic toxoplasmosis this parasitic disease has gained increasing interest. Besides presenting clinical and therapeutical concepts, this volume provides current knowledge about genetics and immunology of T. gondii and the interaction with its 'host'. Since in vivo and in vitro models of toxoplasmosis exist, and genetic manipulation has become possible, this protozoan parasite has recently been accepted as a model for understanding the pathogenesis and persistance of other intracellular parasites. The articles of the book compromise both reviewing current concepts and reporting on yet unpublished results of leading scientists in this field.

This book contains the proceedings of the first meeting on invertebrate immunity ever sponsored as a summer research conference by the Federation of American Societies for Experimental Biology (FASEB). The conference was held in Copper Mountain, CO from July 11-16, 1999. It was a an extension of a New York Academy of Sciences meeting entitled "Primordial Immunity: Foundations for the Vertebrate Immune System" held on May 2-5,1993 at the Marine Biological Laboratories in Woods Hole, MA. The proceedings of that meeting were published in The Annals of the New York Academy of Sciences (volume 712). At that meeting all the attendes agreed that this type of conference (a relatively small focused gathering) allowed for participation by investigators at all levels of their careers. We further agreed that we should search for a forum that would allow this meeting to continue. The FASEB Summer Research Conference was an excellent vehicle for this type of meeting. Furthermore, this year's participants decided to continue this meeting as a regularly scheduled FASEB sponsored event. This was a unique conference in the sense that it focused upon mechanisms of development and defense in protostome and deuterostome invertebrates and lower vertebrates. There was a strong emphasis on evolutionary cell biology, phylogenetic inferences and the evolution of recognition and regulatory systems.

The book appeared in two previous Slovak editions for university students in Czechoslovakia. This edition presents a completely new version updated according to recent advances not only in immunochemistry and essential immunology but also in molecular biology, biochemistry and molecular genetics. The scope of the book is considerable since the goal was to cover the field of immunochemistry from the widest point of view including both the topic and methods of contemporary immunochemistry. Each chapter provides basic information on a specific subtopic, clearly and understandab ly, and presents principles of individual immunochemical methods. I am confident that the book will fill the gap between the books on essential immunology and highly specialised books on individual areas of immunoche mistry (e. g. on antibodies, antigens, numerous immunochemical techniques, etc. ). It may also prove useful for beginning investigators from different biological and medical fields as it supplies basic information needed for solving their scientific problems by immunochemical approaches. I do hope that readers will find the text stimulatory and pleasury to read. I wish to thank all colleagues and friends for supplying their own results, suggestions and for their encouraging comments. My thanks go also to the editors and publishers for their valuable contribution to the preparation of the book. 1 Introduction The term immunochemistry was coined by the Swedish chemist ARRHENIUS who used it for the first time in his lectures in 1907."

Rheumatology is a branch of medicine studying abnormalities and diseases of the musculoskeletal system: Joints, muscles, and connective tissues. Immunology is a branch of medicine studying abnormalities and diseases of our immune system. Immune diseases are either due to deficiency of the immune system leading to "immunodeficiency" or due to failure of recognizing the "self" from "non-se'f" and attacking the own system, leading to "autoimmune disease," or due to hypersensitivity diseases such as allergic rhinitis. Rheumatic and Immunologic diseases are closely related because the underlying etiology of certain rheumatic diseases is abnormality of the immune system. Understanding the immune system is the key factor in recognizing the abnormalities in rheumatic diseases. Therefore, clinical immunologists and rheumatologist may occasionally see and treat similar conditions. In fact some specialists are dually trained in Allergy/Immunology and Rheumatology. What makes these two branches of medicine different is their uniqueness. Rheumatologists for example evaluate and treat arthritis (diseases of the joints) such as rheumatoid arthritis, osteoarthritis, and fibromyalgia, to name a few. Allergists and clinical Immunologists treat hypersensitivities such as allergic rhinitis, bee sting allergy, and allergic asthma, and immunological diseases such as immunodeficiencies among others. Both specialists, however deal with autoimmune diseases. Why a Book in Immunology and Rheumatology? Our musculoskeletal structure holds and protects our internal organs. Any insult to such structure, excluding acute bone fractures, results in various conditions known as rheumatic diseases. Whether the involved area is a joint, a cartilage, or a muscle, the understanding of the immune system helps to elucidate the mechanisms of such diseases. As the population ages in the 21st century, the role of rheumatology and Immunology becomes more apparent and appreciated. Approaching a patient with multiple rheumatic diseases is not an easy task. In fact our immense system is perhaps the most complicated system of the human body; this is due to presence and interactions of myriad of cells and chemical mediators that participate in complex pathways such as the inflammatory response and others to defend the body and respond to pathogens. In addition, our immune system protects us against further exposure to harmful substances. Although there are several books on the subjects of immunology and rheumatology, this case-based study of these two subjects is a unique way of reviewing and discussing such complicated areas of medicine. The Book Format: This book will be divided into 6 parts and 16 chapters. The Estimated length: 300-350 manuscript pages. As with the previous titles I have edited (and which have received very favorable reviews), each chapter will consist of 2 or more cases with discussion, and 5 multiple choice questions per case. This title will be similar to Challenging Cases in Pulmonology (Springer 2011), and Challenging Cases in Allergic and Immunologic Diseases of the Skin (Springer, 2010), Challenging Cases in Allergy and Immunology (Humana Press, 2009).

Immunofluorescence, a suitable laboratory method for the microscopic demonstration of antigens and antibodies in biological materials, useable, for example, to provide evidence for the pathogenesis of disease in histological or cytological preparations and for tumour cell differentiation. For this reason immunofluorescence has a decisive role as the method of choice for the diagnosis of auto-immune diseases. This primer on immunofluorescence techniques, which first appeared in 1979, is a richly illustrated handbook suitable for everyday practical work in the laboratory, useable as both an introduction to the subject as well as an atlas. In hardly any other area of medicine are there so many new findings to report. The second edition of this book is concerned not only with the detection methods which now form an essential and established part of diagnostic techniques, but also with the most recent research results such as the discovery of antibodies against Auerbach's plexus and against podocytes...

In 1897, Ehrlich suggested that natural preformed receptors from the surface of cells provided immunity to various chemical substances. Many years later, in 1940, Pauling proffered the concept that antibodies comprised a single poly peptide chain and that each end of the protein could form an antigen-binding site. Burnet tried to explain the diversity of antibody specificity by hypothesizing that it was cell-derived. These hypotheses probably have led to as much or more experimentation and discussion than any other of the many conjectures set forth to explain immunity on a molecular and cellular basis. Extensive investigations, initially stimulated by these propositions, proved Pauling's notion incorrect. In its demise, however, the multichain structure of the immunoglobulins was realized. In retrospect it be comes obvious that Ehrlich's idea, though not correct, was borne of amazing logic and cognition. Expansion of Burnet's theory seems to be occurring presently; much excitement is engendered by the finding of cell-bound immunoglobulin receptors. Ouring the preceding dozen years, immunochemists have accumulated enormous quantities of data. Though there is so much yet to be done, as a result of this research one may now discuss antigen-binding sites in relation to the protein's primary structure. There is even considerable understanding of the cellular assembly of some immunoglobulins. Entire books can be written about the chemistry of antigens and of complement."

A remarkable spectrum of novel immunoreceptors sharing related immunoglobulin-like domains and signaling potential has been identified in recent years. These receptors have attracted widespread interest because they resemble the TCR, BCR, and FcR complexes in their ability to serve as activating or inhibitory receptors on the cells that bear them. Moreover, they are well positioned to affect both innate and adaptive immunity. The full range of ligands for these new receptor families is still not known, and understanding of their physiological roles is far from complete. This volume is the first attempt to summarize and highlight all known aspects of immunoglobulin-like receptors, providing a topical overview of the roles and characteristic features of the immunoglobulin-like receptors and related molecules in the immune system. Researchers in immunology, molecular biology, cell biology, clinical medicine, and pharmacology will find this book invaluable.

The fourth annual American Institute for Cancer Research (AICR) conference on diet, nutrition and cancer was held at the L'Enfant Plaza Hotel in Washington, D. C. , September 2~3, 1993. In keeping with present concerns and in line with current trends, the theme was "Diet and Breast Cancer. " This proceedings volume is comprised of chapters from the platform presentations of the two day conference and abstracts from the poster session held at the end of the first day. Experimentally, there is sufficient evidence to support a relationship between dietary fat and the risk of breast cancer. A meta-analysis was provided by data from 114 experiments with over 10,000 animals, divided into groups fed ad libitum on diets with different levels or sources of fat, or different levels of energy restriction. This exercise suggested that linoleic acid was a major determinant of mammary tumor development but that other fatty acids also enhanced mammary tumor development in animals. However, as mentioned by several speakers, results from epidemiological studies often are conflicting, thus leading to confusion among both health professionals and the public. Surveys of specific populations which have migrated from countries with low breast cancer rates to those with higher rates are often some of the most compelling studies with respect to a high fat diet-breast cancer association. Nonetheless, various cohort and prospective studies, some quite large, did not appear to show a relationship between consumption of fat (any type) and breast cancer.

The 11th International Conference on Lymphoid Tissues and Immune Reactions was held in Spa-Liege (Belgium), from 4 to 8 July 1993. The regular devotees refer to these conferences as the "Germinal Centre Conferences or GCC". In the 1960s, the germinal centres were the subject of such considerable study and speculation that a group of dynamic people decided to devote an international conference centered on that topic. This led to the fIrst GCC organized in Bern in 1966. Following the success of this initial meeting, further sessions have been organized at regular intervals and, over the years, the scope of the GCC has been broadened. Nowadays, the GCC conferences are dedicated to in vivo immunology and deal mainly with cellular, functional and molecular aspects of the lymphoid system. The credo of these conferences is "in vivo veritas," implying that the sole investigation of components (like molecules or cell populations) only gives a partial truth. Ultimately, the components have to be explored in their global context in order to see how they interact with other parts and how they are integrated as a whole to ensure the homeostasis of the immune system. In 1966, the GCC lasted 3 days and included 57 contributions "which were discussed at length. " The present conference lasted 4 days and accommodated 2 honorary lectures, 80 free papers and 209 poster presentations. Out of those presentations, a selection was performed by the Chairpersons to compose the present volume.

The means by which non-enveloped viruses penetrate cellular membranes during cell entry remain poorly defined. Recent findings indicate several members of this group share a common mechanism of membrane penetration in which the virus particle undergoes programmed conformational changes, leading to capsid disassembly and release of small membrane-interacting peptides. A complete understanding of host cell entry by this minimal system will help elucidate the mechanisms of non-enveloped virus membrane penetration in general

New Bacterial Vaccines focuses upon unfulfilled needs for bacterial vaccines. The increase in drug resistance among many bacterial species has increased the need for new bacterial vaccines. This book serves as a comprehensive reference on the major aspects of developing new bacterial vaccines. The distinctive feature of this book is that it focuses upon new vaccines now under development by reviewing key issues for each vaccine target and new technologies being applied to developing new vaccines. This book should prove useful for students in the life sciences, scientists, developers of vaccines and biotechnology products, clinicians, regulators, and health-care practitioners.

Autoimmune myasthenia gravis (MG) is a classical autoimmune disease, for which the target antigen, nicotinic acetylcholine receptor, has been cloned, sequenced and biochemically characterized. Antibodies to acetylcholine receptors destroy acetylcholine receptor at the neuromuscular junction, thus leading to defective neuromuscular transmission, muscle fatigue, and weakness. In the last few years, rapid advances have been made in unraveling the cellular and molecular mechanisms involved in the pathogenesis of MG, both in the animal model, experimental autoimmune MG (EAMG), and in human MG. Significant advances are being made in characterizing the cells and molecules involved in the autoimmune response to the acetylcholine receptor (AChR). These advances are leading to the development of specific methods of immunointervention in EAMG. Further understanding of the intricate involvement of the major histocompatibility complex (MHC) and non-MHC genes, T cell receptors (TCR), costimulator molecules, and specific cytokines in the afferent and efferent autoimmune response of AChR should pave the way to future antigen/clone-specific therapy of MG. This book is the outcome of the MG workshop proceedings in Mysore, India, 1998. The majority of the chapters in this book are contributed by world-renowned authors and their students. The book not only contains a timely review of specific topics, but also up-to-date findings. Immunologists and neurologists will find, in this volume, the latest in MG/EAMG cutting-edge research. Clinicians will be interested in the applications of the various immunointervention strategies into clinical trials in MG patients. Finally, students will not only be interested in reading the latest in EAMG/MG research, but will also find information to help them develop a future strategy to unravel the precise mechanism of disease. To summarize, in this book, the readers should find up-to-date information related to immunological mechanisms involved in MG pathogenesis and various modalities for possible approaches to immunointervention to treat MG.

Research related to the pineal gland has advanced rapidly in the last three decades since the discovery of its most important hormone, melatonin. This indoleamine has been shown to have a large variety of effects in the organism; the bulk of these actions were initially thought to relate the pineal gland to the reproductive and endocrine systems. It is now apparent, however, that the physiologic interactions of the pineal and its hormones far transcend its control of endocrine function. One field of pineal research that has developed rapidly within the last 5 years has been the demonstration of its relationship to the immune system. Since the pineal gland is part of the central nervous system, these observations generally fall in the category of neuroimmunology, an area that, in its own right, has received a great deal of attention in the last decade. Thus, a NATO Advanced Study Course entitled "Role of Melatonin and Pineal Pep tides in Neuroimmunomodulation" was convened in Erice, Sicily, on June 3-9, 1990. This book is a result of the scientific presentations given at the workshop. The contributions to the book include mini-review articles which summarized the presentations of the invited speakers as well as a selected number of brief communications where the subject matter was in line with the theme of the Advanced Study Course.

This volume is ideal for individuals interested in taking an in-depth look at how cytokines and chemokines participate in autoimmune disorders, and how cytokines and chemokines can be used as targets for therapeutic intervention. The outstanding features of this book are that it is divided in chapters each focusing on specific, highly prevalent autoimmune disorders. The role of cytokines and chemokines in each of these disorders is dissected in the context of the autoinimune responses that drive these diseases. Importantly, each chapter is meant to provide an in-depth review of how cytokines and chemokines participate in each disease, rather than very specific aspects of cytokine or chemokine biology. The book therefore provides an integrated view of how multiple cytokines and chemokines participate in the initiation and evolution of both systemic and organ-specific pathological immune responses.

Reproductive Immunology is a compilation of research articles presented during the VII International Congress of Reproductive Immunology which was held in New Delhi, India on 27-30 October 1998. The articles pertain to the following six major themes: Molecular and Immunological Aspects of Sperm-Egg Interaction Embryonic-Endometrial Cross-Talk Immunobiology of Pregnancy Autoantibodies and Infertility Immunocontraception Mucosal Immunology and Reproductive Tract Infections . The first section deals with our current understanding of various steps involved in fertilization. The functional significance of sperm surface mannosidase and glutathione S-transferases to bind zona pellucida is described. The role of zona pellucida glycoproteins in the binding of sperm, induction of acrosome reactions and avoidance of polyspermy is discussed. In the second section, the role of various cytokines, growth factors and immunomodulatory agents in implantation of embryos is described. In the field of reproductive immunology, one of the major issues is to explore the successful gestation of the histoincompatible fetus in the uterus of an immunologically competent mother. The Proceedings presents the issues of paternal antigens at the feto-maternal interface and shows that Th2-type of immunity is involved in normal successful conception. The role of membrane-bound and soluble HLA-G in protecting the fetus from the lytic activities of maternal uterine and peripheral blood natural killer (NK) cells is also presented. Nature's experiments suggest that antibodies against sperm-specific antigens are responsible for infertility in some women. The possibility that an immunogenetic background contributes to production of sperm-immobilizing antibodies in infertile women is discussed in the section on autoantibodies and infertility. The Proceedings presents the issue of Th1-type cytokines in inducing recurrent spontaneous abortions of unexplained etiology. The roles of β2-glycoprotein 1 (β2-GP1)-dependent anticardiolipin antibody, lupus anticoagulant, antiphospholipids, anti-thyroid antibody and anti-nuclear antibody in miscarriages are also described. The rising global human population, particularly in the developing countries, has driven the need for new and safer methods of contraception. Fertility regulation by vaccines is thus an interesting proposition. The section on contraceptive vaccines discusses the latest advances in this area and describes the current status of vaccines based on βhCG, sperm antigens, zona pellucida glycoproteins, and riboflavin carrier proteins. The issues of mucosal immunity and strategies for enhancing local genital immune responses to combat HIV infection is discussed. The role of inflammatory and related cytokines in chorioamnionitis is described. The contents of this Proceedings describes various facets of reproductive immunology which will help us to design strategies to combat genital infections and miscarriages caused by immunological etiology. Descriptions of the molecular basis of gamete recognition, implantation and survival of the allogenic fetus will help in designing strategies for overcoming infertility and also new contraceptive approaches. The Proceedings will be useful to researchers and clinicians involved in basic or applied research in the disciplines of reproductive biology, reproductive immunology, and obstetrics and gynecology.

Infection with the human immunodeficiency virus (HIV) and human T-cell lymphotropic virus type I (HTLV-I) is known to be associated with an increased risk of neoplastic disorders, especially Kaposi's sarcoma and aggressive B-cell lymphoma for the former, and T-cell lymphoma for the latter. The information obtained from the study of these infections has led to remarkable advances in our understanding of the immune system, as well as the biology of human neoplasms. The management of malignant diseases in such patients also poses substantial challenges to clinicians. This book provides an overview of the epidemiology, biology, clinical features, and clinical management of neoplasms occurring in such individuals. It is an important resource for clinicians treating these diseases, and for basic scientists who have an interest in this field.

COX-2 inhibitors are important drugs with analgesic and anti-inflammatory effects. The discovery of COX-2, the evolution of drug development in this field and the implications of these developments in patient therapy are topics of this volume. This book presents both pre-clinical and clinical information and is important for clinicians interested in the latest information about this class of drugs, for researchers and for students in the field.