Research into and interest in the role of stromal cells in immunology has exploded over the past 15 years. The conventional view that placed non-hematopoietic stromal cells as passive, structural, and supportive entities has now been replaced with an appreciation that these cells have active, dynamic roles during immune responses, and thus impact on the pathophysiology of multiple immune-mediated diseases. This book serves to provide solid grounding in the fundamentals of stromal immunology, focusing on the biological aspects of their function in addition to highlighting key areas for the development of the field in the future. The book is also a unique source of information on emerging concepts that place stromal cells from outside lymphoid organs as major contributors to the biology of diverse conditions, such as rheumatoid arthritis, chronic parasitic infection, inflammatory bowel disease, and cancer.

The incidence of insulin-dependent diabetes mellitus (100M) varies dramatically across racial groups and countries, with annual age-adjusted rates of approximately 40/100,000 per year in Finland, but only 0.51100,000 per year in China. Although reasons for these marked geographic differences are unknown, it is likely that genetic variations across populations play a m or role. To determine the contribution of genetic factors to the global patterns of 100M incidence, international comparative studies are now being undertaken as part of the WHO Multinational Project for Childhood Oiabetes, known as the DIAMOND Project. It is, therefore, necessary to develop and implement epidemiologic standards for these investigations which can be applied across populations. This will ensure that comparable data are obtained in all countries, and that relevant scientific questions can be properly addressed. The development of standards for molecular epidemiologic studies of 100M is the of the NATO Advanced Research Workshop. During this meeting at the objective University of Pittsburgh, scientists from across the world convened to discuss issues relating to the standardization of: 1. the collection of family history data to assess the risk of 100M in first degree relatives, 2. case-control molecular epidemiology studies of 100M susceptibility, 3. HLA family studies, 4. laboratory methods and ONA technology transfer for genetic marker evaluations.

The neuromuscular diseases comprise the disorders of peripheral nerves, the neuromuscular junction, and muscle. Both pre- and post-synaptic elements of the neuromuscular junction may become targets of autoimmune attack in different diseases. This book addresses the immunologically-mediated neuromuscular diseases, including Guillain-Barre syndrome and other autoimmune neuropathies, the Lambert-Eaton myasthenic syndrome, myasthenia gravis, and the autoimmune diseases of muscle. Two chapters are devoted to the vasculitic and HIV-mediated neuromuscular diseases. The experimental models of neuritis and myasthenia gravis are addressed in separate chapters. An introductory chapter provides a general background to autoimmunity. This book aims to be a useful overview for all neurologists, rheumatologists and immunologists both in research and clinical practice.

Progress in basic and clinical immunology within the last two decades has provided profound insight into the immune system and its role in preventing endogenous and exogenous damage. In contrast, disbalances within this system can result in autoimmune disorders which may affect diverse organs and result in distinct clinical pictures. In many of these, however, the individual etiopathogenetic mechanisms are poorly understood and even more their clinical symptoms are hard to treat. The book offers insight into basic mechanisms of autoimmune disorders. It includes neurological, gastrointestinal, ophthalmological and skin diseases as well as current and future therapeutic options including immunomodulatory drugs and different vaccination strategies. By addressing diverse organ systems, both singular and shared features are elaborated. Thus an exchange of ideas is intended across research on single organ systems within a truly interdisciplinary setting.

The field of DNA vaccines has undergone explosive growth in the last few years. As usual, some historical precursors of this approach can be d- cerned in the scientific literature of the last decades. However, the present state of affairs appears to date from observations made discreetly in 1988 by Wolff, Malone, Felgner, and colleagues, which were described in a 1989 patent and published in 1990. Quite surprisingly, they showed that genes carried by pure plasmid DNA and injected in a saline solution, hence the epithet "naked DNA," could be taken up and expressed by skeletal muscle cells with a low but reproducible frequency. Such a simple methodology was sure to spawn many applications. In a separate and important line of experimentation, Tang, De Vit, and Johnston announced in 1992 that it was indeed possible to obtain humoral immune responses against proteins encoded by DNA delivered to the skin by a biolistic device, which has colloquially become known as the "gene gun. " The year 1993 saw the publication of further improvements in the me- ods of naked DNA delivery and, above all, the first demonstrations by several groups of the induction of humoral and cytotoxic immune responses to viral antigens expressed from injected plasmid DNA. In some cases, protection against challenge with the pathogen was obtained. The latter result was - questionably the touchstone of a method of vaccination worthy of the name.

This book presents methodological and application research in detecting cellular and molecular biophysical properties based on atomic force microscopy (AFM) nanorobotics. Series methods for in situ label-free visualizing and quantifying the multiple physical properties of single cells and single molecules were developed, including immobilization strategies for observing fine structures of living cells, measurements of single-cell mechanics, force recognition of molecular interactions, and mapping protein organizations on cell surface. The biomedical applications of these methods in clinical lymphoma treatments were explored in detail, including primary sample preparation, cancer cell recognition, AFM detection and data analysis. Future directions about the biomedical applications of AFM are also given.

This essential volume explores mesenchymal stem cells (MSCs) and their potential to suppress immune-mediated inflammation. The chapters examine applications in autoimmune diseases such as lupus, rheumatoid arthritis and multiple sclerosis; blood cancers such as leukemia and lymphoma; and reproductive complications, specifically pre-term labor and use of MSCs in vitro and in animal models to discover methods of suppressing the causal inflammatory response. It also further defines the methodologies required to develop research on MSCs in vitro into established preclinical animal models including those which are proven replicas of autoimmunity and pre-term labor, to name but two. Mesenchymal Stem Cells and Immunomodulation, part of Springer's Stem Cell Biology and Regenerative Medicine, is an invaluable resource for researchers and clinicians working with stem cells, autoimmune disease, oncology, and reproductive medicine.

Although there have been many books on HIV and AIDS, surprisingly little has been published that focuses on the immunology of retroviral infections in general, and HIV in particular. Retroviral Immunology: Immune Response and Restoration is the first book of its kind to address the most important aspects of the immunology of retroviruses, including not only the virus-specific immune responses, but also genetic and virologic factors modulating these responses. The book also deals directly with the emerging concept of immune restora tion in retroviral infections, a particularly important subject to the thousands of clinicians who deal with this problem on a daily basis. With the advent of highly effective antiviral drug regimens to slow down the replication of HIV and the progression of AIDS, new challenges and opportunities are arising. Restoration of general immune function has brought with it not only complica tions of immune restoration-mediated disease, but also the realistic hope for meaningful restoration of the ability to control HIV replication with the immune system. Leading scientists in the field have summarized the most current informa tion regarding experimental and clinical aspects of retroviral infections. Retroviral Immunology: Immune Response and Restoration should prove an impor tant point of reference for basic scientists and clinicians in this area of research. We are indebted to all of our authors for their excellent contributions."

Despite wide recognition as a serious public health problem, anaphylaxis and hypersensitivity reactions remain under-recognized and under-diagnosed. This book fills the gaps in our understanding of the identification of triggers, recognition of clinical presentations, understanding of the natural history of these reactions, and selection of treatment strategies including those focused on cellular and molecular targets. The book provides a detailed examination of disease etiology, pathogenesis, and pathophysiology and their correlation to clinical practice. Forefront knowledge of the mediators and mechanisms of anaphylaxis is covered with an emphasis on how new discoveries shape our current and emerging therapies.

This text discusses mathematical modelling, analysis and control of the immune system and disease dynamics. The purpose of the book is the practical application of mathematics to immunology and medicine in order to establish a basis for more effective treatment, to provide a tutorial systematic description of how the immune system controls diseases and to present several significant examples such as malignant tumour dynamics and control, and viral hepatitis. The book is multidisciplinary in content, with the intended readers including biomathematicians, biologists and physicists. It combines immunological principles, mathematical models, computer simulations and methods of analysis.

This book incorporates the latest advances in immunopharmacological treatment. One objective has been to provide appropriate bridges between the basic sciences of immunology and pharmacology on the one hand and clinical medicine on the other. A further intention has been to emphasize those advances in immunology and pharmacology that are of clinical importance while retaining those facts that, while not new, remain clinically useful. The immunology section provides the necessary background for immunopharmacologi cal treatment. The chapters on individual cell types include normal surface markers, mode of activation, and activation markers and functions in health and disease. The chapters on pharmacology give comprehensive information on immunosuppressive drugs in regular use today, their biochemical and cellular mechanisms of action, pharmaco kinetics, dosage regimens, therapeutic responses, adverse reactions, and drug interactions and tolerance. In addition, certain therapeutic principles that are still in an experimental phase are described, for example, immunotoxins, thymic hormones, and interleukins. The book presents comprehensive information on various autoimmune diseases, the etiopathogenetic immune mechanisms where these are known, and the current possibilities for immunopharmacological intervention. The specific disease section also covers rare situations, fluctuations in disease patterns, and subgroups of patients and immunophar macological treatment in these situations. Altogether, the book represents a practical textbook for clinicians and advanced students who want to be updated on therapeutic principles with regard to autoimmune diseases and transplantation."

Pathogenic bacteria for human and animals have developed sophisticated weapons, termed virulence factors, to ensure their replication and persistence into their hosts. The authors in this volume show a synthesis on how the various host cellular Rho GTPases activities are manipulated by bacteria to fulfil their virulence.

This second edition volume expands on the first edition with new developments on Toll-Like Receptors (TLRs) controlling events such as cross-priming of associated pattern recognition receptors, post-transcriptional regulation, interaction with other cellular and biologic systems, and cancer progression. This book is divided into five sections: Part I outlines methods for TLR detection, interaction, and intracellular trafficking; Part II describes methods and assays to investigate how TLRs cross-prime other pattern recognition receptors, including intracellular DNA receptors and inflammasome formation; Part III highlights RNA regulation, detailing how TLRs can induce RNA transcripts and molecules such as lncRNAs and microRNAs; Part IV explores TLR detection and activation in systems such as epithelial barrier function, metabolism and the circadian clock, as well as cellular systems including T and B lymphocytes; and Part V describes models to delineate the role of TLRs in diseases such as dermatitis, arthritis, and gastric cancer. Written in the highly successful Methods in Molecular Biology series format, each chapter contains a summary, a list of required materials, step-by-step, readily reproducible laboratory protocols, useful notes to investigate TLRs in cell culture, systems and disease, and tips on troubleshooting and avoiding known pitfalls. Practical and cutting-edge, Toll-Like Receptors: Methods and Protocols, Second Edition is a valuable resource to any immunologist, molecular or medical biologist working in a laboratory setting. It will add skill to both students and the more advanced molecular biologist who wishes to learn a new technique or move to a different area within their current repertoire of practical knowledge.

In contrast to the substantial literature that focuses upon innate immune signaling in the gut, there is remarkably less known about the response of the airway to bacterial pathogens. The purpose of this book will be to review the current status of theunderstanding of the pathogenesis of acute bacterial pneumonia, slanted toward the mucosal immunology of these infections. It will describe, in general, the signaling cascades that control the proinflammatory response to bacterial infection in the lung. How innate immune signaling is orchestrated in response to specific common airway pathogens is addressed, targeting Staphylococus aureus (including MRSA), Streptococcus pneumoniae and Klebsiella pneumoniae. By describing the general immunological responses to conserved bacterial components and then detailing how specific organisms cause infection, this book provides a targeted but comprehensive review of this important topic.

Proceedings of a NATO ASI held in Erice, Italy, April 27-May 1, 1995.

Despite rapid increases in knowledge, malaria continues to kill more than a million people each year and causes symptomatic disease in a further 300 million individuals. This volume brings some of the world's best investigators to describe recent advances in both the scientific and clinical aspects of malaria, and bridges between the two.

This second edition provides updated and new chapters on T-Cell trafficking. In addition to detailed experimental procedures, the interested reader will find informative introductory chapters on the relevance of T-Cell trafficking in thymic population and maturation, traffic through secondary lymphoid organs during 'physiological' resolving inflammation and during immune responses, as well as T-Cell trafficking in chronic inflammatory diseases. Importantly, chapters cover methods from in silico modeling of cellular interactions, in vitro adhesion assays, through ex vivo functional assays to integrated intravital modeling of T-Cell trafficking through organs. Written in the highly successful Methods in Molecular Biology series format, each methods chapter includes a short introduction to the topic, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, T-Cell Trafficking: Methods and Protocols, Second Edition aims to be an essential point of reference for those new to the field of T-Cell trafficking, or to those looking to expand their technical capabilities.

Theodosius Dobzhansky's statement that nothing in biology makes sense except in the light of evolution, also applies to the major histocompatibility complex (MHC). This book presents up-to-date, state-of-the-art reviews on diverse topics pertinent to MHC evolution, including the organization of the MHC in humans and other model vertebrates, the nature and origin of MHC polymorphism, MHC-parasite co-evolution, and the origin of the adaptive immune system. The book will be of interest not only for immunologists, geneticists, and evolutionary biologists, but also for other specialists who want to keep abreast of the latest developments in this rapidly expanding field.

Organs and tissues that can tolerate little or no inflammation have developed multiple overlapping mechanisms of immune protection in the absence of inflammation. These areas have been designated immune-privileged sites by Peter Medawar and include the central nervous system, eye, reproductive tract, testis and possibly the liver. Mechanisms of immune homeostasis found in less immune-regulated organs are often evident in the immune privileged sites and vice versa. It is important that the non-inflammatory mechanisms that contribute to immune privilege allow host defense against infectious organisms.

This volume highlights the mechanisms leading to immune privilege in tissues and organs, the deviation of immune responses and the modification of the behavior of the immune cells that manage to cross the blood barriers of tissues, in the context of infection.

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The increasing incidence and prevalence of allergic disease worldwide is one of the most remarkable phenomena of the past 50 years. One in three people in developed countries will experience an allergic condition at some point in their lives and advances in understanding the causes of this trend, and in allergy treatment and care, have captured the imagination of scientists, clinicians and the public. Landmark Papers in Allergy is a definitive collection of over 90 papers charting key discoveries and scientific advances in relation to allergy and the development of treatment and care for allergic disorders. Comprehensive in its coverage, the book includes the first clear descriptions of allergic diseases; the major advances in treatments, such as the discovery of antihistamines, cortisone, biological therapies and immunotherapy; the great immunological advances, such as the discovery of immunoglobulin E (IgE) and leukotrienes; the possible factors behind the increase in allergy, such as the house dust mite, changes in hygiene and diet; and the growing understanding of the social, psychological and quality-of-life consequences of allergy. Including authoritative commentaries from leading international experts providing reflections on the historical importance and current relevance of each landmark paper, Landmark papers in Allergy is essential reading for any clinician or academic with an interest in allergy.

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.

Connective tissue diseases demand study because of their frequency, morbidity and mortality. They present intriguing challenges in the fields of diagnosis, management and research. Their range has now expanded enormously so that no individual can master the whole subject, particularly as this relates to their immunological basis. Immunology of Connective Tissue Diseases has been written by experts who are either clinical or basic scientists. The book presents up-to-date reviews of the immunological basis of connective tissue diseases as it impacts on diagnosis, pathogenetic concepts, disease monitoring and management. The book is aimed at physicians interested in understanding the immunological basis of these diseases, and at immunologists who are either entering this field for the first time and would like to have a convenient state-of-the-art account of its status, or who are researching in one area and would like to acquaint themselves with the developments which have taken place in others.

During the last decade or so vaccine development has been facilitated by rapid advances in molecular and cell biology. These have laid the foundations of a new generation of vaccines exemplified by subunit vaccines produced through gene cloning and by synthetic peptides mimicking small regions of proteins on the outer coat of viruses. Such peptide~ are capable of eliciting virus-neutralizing antibodies. Unfortunately, subunit and peptide vaccines are only weakly or non immunogenic in the absence of immunological adjuvants that are known to augment specific cell-mediated immune responses to the antigens and to promote the formation of protective antibodies. This book contains the proceedings of the 4th NATO Advanced Studies Institute (ASI) "Vaccines: New Generation Immunological Adjuvants" held at Cape Sounion Beach, Greece, during 24 June -5 . July 1994 and deals in depth with both theoretical and practical aspects of vaccinology. These include the role of antigen presenting cells in the induction of immune responses. immunopotentiation by a variety of new generation immunological adjuvants and vaccine carriers. and recent advances and perspectives in experimental vaccines as well as vaccinatioll with nucleic acids. We express our appreciation to Dr. K. Dalsgaard and Dr. J. L. Virelizier for their cooperatioll in planning the ASI and to Mrs. Concha Pening for her excellent production of the manuscripts. The ASI was held under the sponsorship of NATO Scientific Affairs Division and generously co-sponsored by SmithKline Beecham Pharmaceuticals (Philadelphia).