The book covers recent developments in research and practice of allergy and immunology. Special emphasis has been given to epidemiology and the relation of genetic and environmental factors in allergic diseases. Occupational aspects and the pathophysiology are additionally covered and an overview of the current pharmacotherapy and immunotherapy is provided.

It has been known for a number of years that not only pathogenicity islands but also plasmids and bacteriophages are able to carry genes whose products are involved in pathogenic processes. Accordingly, such elements and their products play an important role in pathogenesis due to the intestinal E. coli as well due to Shigellae. Another interesting aspect which is reflected in different articles is that genomes evolve by acquisition of new pieces of DNA following gene transfer, but also by genome reduction. Different mechanisms include the deletion of sequences or the elimination of functions by the accumulation of point mutations or rearrangements.

Two decades have passed since the mechanisms of protein synthesis became well enough understood to permit the genetic modification oforganisms. An impressive amount of new knowledge has emerged from the new technology, but much ofthe promise of20years ago has notyet been fulfilled. In biotechnology, efforts to increase the yields of commercially valuable metabolites have been less successful than ex pected, and when they have succeeded it has often been as much from selective breeding as from new methods. The cell is more complicated than what is presented in the classical teaching of biochemistry, it contains more structure than was dreamed of 20 years ago, and the behaviour ofany systemofenzymes is more elaborate than can be explained in terms ofa single supposedly rate-limiting enzyme. Even if classical enzymology and meta bolism may have seemed rather unfashionable during the rise ofmolecular biology, they remain central to any modification ofthe metabolic behaviour oforganisms. As such modification is essential in much ofbiotechnology and drug development, bio technologists can only ignore these topics at their peril."

Now available in its Third Edition, Asthma: Basic Mechanisms and Clinical Management has become "the" reference text in asthma. This highly successful text sheds new light on the basic physiological and molecular mechanisms of asthma, how current treatments work, and how best to apply the latest knowledge to control this important disease. The Third Edition has undergone radical revision and includes several new chapters. It retains the virtues of the previous volumes by bringing together all of the recent research findings by internationally recognized experts on the causative mechanisms of asthma, including in-depth clinical aspects and therapy. The book presents an integrated approach toward the treatment of this disease with new concepts, changes in asthma management, and the development of new therapeutic agents. Asthma provides extensive references for researchers and clinicians who need to keep abreast of recent developments in this rapidly expanding field.
Key Features
* Comprehensive coverage of both basic science and clinical aspects of asthma
* Extensively referenced throughout

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.

The Endoplasmic Reticulum (ER) is an organelle with extraordinary signaling and homeostatic functions. It is the organelle responsible for protein folding, maturation, quality control and trafficking of proteins destined for the plasma membrane or for secretion into the extracellular environment. Failure, overloading or malfunctioning of any of the signaling or quality control mechanisms occurring in the ER may provoke a stress condition known as ER stress . Accumulating evidence indicates that ER stress may dramatically perturb interactions between the cell and its environment, and contribute to the development of human diseases, ranging from metabolic diseases and cancer to neurodegenerative diseases, or impact therapeutic outcome. This book primarily focuses on the pathophysiology of ER stress. It introduces the molecular bases of ER stress, the emerging relevance of the ER-mitochondria cross-talk, the signaling pathways engaged and cellular responses to ER stress, including the adaptive Unfolded Protein Response (UPR), autophagy as well as cell death. Next the book addresses the role of ER stress in physiology and in the etiology of relevant pathological conditions, like carcinogenesis and inflammation, neurodegeneration and metabolic disease. The last chapter describes how ER stress pathways can be targeted for therapeutic benefit. Altogether, this book will provide the reader with an exhaustive view of ER stress biology and the latest insights in the role of ER stress in relevant human diseases."

Engineered antibodies currently represent over 30% of biopharmaceuticals in clinical trials and their total worldwide sales continue to increase significantly. The importance of antibody applications is reflected in their increasing clinical and industrial applications as well as in the progression of established and emerging production strategies. This volume provides detailed coverage of the generation, optimization, characterization, production and applications of antibody. It provides the necessary theoretical background and description of methods for the expression of antibody in microbial and animal cell cultures and in transgenic animals and plants. There is a strong focus on those issues related to the production of intrabodies, bispecific antibody and antibody fragments and also to novel applications in cancer immunotherapy.

These proceedings contain selected contributions from the participants to the Fourth International Symposium on Dendritic cells that was held in Venice (Lido) Italy, from Oc tober 5 to 10, 1996. The symposium was attended by more than 500 scientists coming from 24 different countries. Studies on dendritic cells (DC) have been greatly hampered by the difficulties in preparing sufficient cell numbers and in a reasonable pure form. At this meeting it has been shown that large quantities of DC can be generated from precursors in both mice and humans, and this possibility has enormously encouraged studies aimed to characterize DC physiology and DC-specific genes, and to employ DC therapeutically as adjuvants for im munization. The possibility of generating large numbers of autologous DC that can be used in the manipulation of the immune response against cancer and infectious diseases has tremendously boosted dendritic cell research and the role of DC in a number of medi cal areas has been heatedly discussed."

Contents. List of Contributors. Brian Henderson and Gerry Higgs: Targets for modulating cytokine responses in inflammatory and infectious diseases. Mary Lee MacKichan and Anthony L. DeFranco: Cell signalling and cytokine induction by lipopolysaccharide. Rodger A. Allen and Stephen E. Rapecki: Regulation of cytokine production by inhibitors of cell signalling. Stanley T. Crooke: Oligonucleotide-based drugs in the control of cytokine synthesis. Peter I. Croucher, Ingunn Holen and Philip G. Hargreaves: Inhibiting cytokine-processing enzymes. Amanda Suitters and Roly Foulkes: Cytokine-neutralizing therapeutic antibodies. Ravinder N. Maini: The debut of anti-TNF therapy of rheumatoid arthritis in the clinic. Anthony Meager: Blockade of cytokine activity by soluble cytokine receptors. Michael F. Smith Jr.: Interleukin-1 receptor antagonist. Raymond J. Owens and Simon Lumb: Therapeutic regulation of cytokine signalling by inhibitors of p38 mitogen-activated protein kinase. Christian Bogdan, Yoram Vodovotz and John Letterio: TGF-ss and IL-10: inhibitory cytokines regulating immunity and the response to infection. Brian Henderson: Therapeutic control of cytokines: lessons from microorganisms. Index

This book covers lymphoproliferative disorders in patients with congenital or acquired immunodeficiencies. Acquired immunodeficiencies are caused by infections with the human immunodeficiency virus or arise following immunosuppressive therapy administered after organ transplantation or to treat connective tissue diseases such as rheumatoid arthritis. It was recently discovered that various diseases or therapeutic modalities that induce a state of immunosuppression may cause virally driven lymphoproliferations. This book summarizes for the first time this group of immunodeficiency-associated lymphoproliferations.

This book covers all aspects of oxygen delivery to tissue, including blood flow and its regulation as well as oxygen metabolism. Special attention will be paid to methods of oxygen measurement in living tissue and application of these technologies to understanding physiological and biochemical basis for pathology related to tissue oxygenation. This book is multidisciplinary and designed to bring together experts and students from a range of research fields including biochemical engineering, physiology, microcirculation, and hematology.

Antibiotics are truly miracle drugs. As a class, they are one of the only ones that actually cure disease as opposed to most drugs that only help relieve symptoms or control disease. Since bacteria that cause serious disease in humans are becoming more and more resistant to the antibiotics we have today, and because they will ultimately become resistant to any antibiotic that we use for treatment or for anything else, we need a steady supply of new antibiotics active against any resistant bacteria that arise. However, the antibiotics marketplace is no longer attractive for large pharmaceutical companies, the costs of development are skyrocketing because of ever more stringent requirements by the regulatory agencies, and finding new antibiotics active against resistant strains is getting harder and harder. These forces are all combining to deny us these miracle drugs when we need them the most. I provide a number of possible paths to shelter from this perfect storm.

Essentials of Mucosal Immunology presents basic concepts as well as new and exciting advances in mucosal immunology and inflammation, the development of mucosal vaccines, and the role of the immune system in mucosal disease. Specific chapters highlight novel approaches to the treatment of autoimmune disease, including the use of oral tolerance; approaches to and vectors for new vaccines; and current concepts in mucosal inflammation and its role in inflammatory bowel disease and ulcer disease.
Key Features
* Contains the most current research on mucosal immunology and is comprehensive in scope
* Includes ideal coverage of both the basic and clinical aspects of the mucosal immune system
* Provides an understanding of the mucosal immune system with regard to new treatments and preventative methods, including vaccine development
* Includes contributions from an international team of experts

The three years since our last conference in San Francisco have again seen a dramatic expansion of the number of antivirals either licensed or in the late stages of clinical trials. d4T is now licensed for HIV infection, famciclovir and the oral pro-drug of acyclovir, valacyclovir, are now licensed for VZV infections in some countries. Moreover. oral ganciclovir, cidofovir, and sorivudine are not far behind. Clinical trials with the second-site reverse transcriptase inhibitors and the protease inhibitors for HlV infection are proceeding rapidly and on a broad scale, and the preliminary results would suggest that several of these classes of drugs will be licensed as well. Despite this optimism, however, there is increasing evidence that antiviral-resistant strains of pathogenic viruses will be a significant problem, perhaps especially with therapy of HIV infection, and there remains a desperate need for improved drugs (with either improved efficacy or decreased toxicity, or both) for CMV and HIV infections. This book is the edited proceedings of the Fourth Triennial Conference on Antiviral Chemotherapy, held in San Francisco, in November 1994. The conference was sponsored by the University of California, San Francisco, and co-sponsored by the International Society for Antiviral Research (ISAR), the Macfarlane Burnet Centre for Medical Research in Melbourne, Australia, and the Australian National Centre for HIV Virology Research. The conference had been organized to present an overview of the field of antiviral chemotherapy.

Of the many special roles played by proteolytic enzymes in immune reactions, this study addresses different aspects of membrane peptidases, signal transduction via ligation of membrane peptidases (especially of dipeptidyl peptidase IV/CD26 and aminopeptidase N/CD13), and regulation of membrane peptidases in vivo and in vitro. A number of newly discovered peptidases (including cathepsin F, W and X, carboxypeptidase X, attractin) are described, with special emphasis given to the role of peptidases in immune and defense reactions and in the pathogenesis of inflammatory and other diseases, including rheumatoid arthritis, pancreatitis, multiple sclerosis, Alzheimer's disease and tumours of various origins. The focus on the involvement of a selection of proteolytic enzymes in immune reactions and diseases is a useful feature of this multifaceted work , which combines biochemical, immunological and clinical research reports with literary reviews of the field.

In the post genomic era, understanding of the innate immune system is enriched by findings on the specificity of innate immune reactions as well as to novel functions that do not strictly correlate with immunological defense and surveillance, immune modulation or inflammation. This volume covers natural killer cells, mast cells, phagocytes, toll-like receptors, complement, host defense in plants and invertebrates, evasion strategies of microorganisms, pathophysiology, protein structures, design of therapeutics, and experimental approaches.

The once-dreaded scourge of smallpox has been eradicated through barrier immunization. The eminent scientist Edward Jenner (1749-1823) was a pioneer in demonstrating that vaccination was an effective means of preventing smallpox. In the three groundbreaking treatises contained in this volume, originally published between 1798 and 1800, Jenner summarizes his evidence in favor of vaccination and describes individual cases.

Over the past ten years, a number of cytokines and growth factors have proven to be as effective therapeutics. While these products have certainly established recombinant biologics as a major pharmaceutical growth sector, the continued interest in this class of drugs arises from the fact that today we have a far better understanding of the human immune response, both at a cellular and molecular level. This has resulted in a more methodical characterisation of these factors which has given clinical researchers an opportunity to plan Phase 1 clinical trials that can provide substantial information on the activity of the cytokine in humans. Currently, a great deal of effort is also being channelled into identifying cytokines from the various DNA databases. Our major objective for this book is to profile cytokines that have been recently identified. The therapeutic potential of these cytokines based on their known properties will be discussed by the authors. The main aim of this book is to provide...

Signaling through antigen receptor initiates a complex series of events resulting in the activation of genes that regulate the development, proliferation and differentiation of lymphocytes. During the past few years, rapid progress has been made in understanding the molecular basis of signaling pathways mediated by antigen and cytokine receptors. These pathways involve protein tyrosine kinases which are coupled to downstream regulatory molecules, including small guanine nucleotide binding proteins (e. g. p21'OS), serine threonine kinases (e. g. , members of the ERK family), and a large group of transcription factors. More recently, there have been breakthroughs in elucidating the genetic defects underlying three X-linked primary immunodeficiency diseases in humans. This volume surveys aspects of these rapidly developing areas of research. The book is divided into 5 different sections. Section I deals with signaling pathways in B lymphocytes. It includes a contemporary assessment of B cell antigen receptor structures, and discussion of the role of Ig-a/lg-B polypeptides in linking the antigen receptor to intracellular signal transduction pathways. The role of accessory molecules in the regulation of signaling by the B cell antigen receptor is also considered. Section II adopts a similar approach to the analysis of the antigen receptor on T lymphocytes. The importance of specialized signaling motifs in the CD3 polypeptides, mechanisms whereby these motifs may interact with the lymphocyte-specific protein tyrosine kinases, and the downstream consequences of these interactions are reviewed. In addition, the role of antigen-induced apoptosis in the generation of immunological tolerance is discussed.

Immunopharmacology represents the boundary between the immune system and chemical mediators of the inflammatory and neuroendocrine responses. The subject as applied to the respiratory system embraces most of the common non-malignant lung diseases of which asthma and allied disorders are the most prevalent. An understanding of the underlying mechanisms of the disorders provides rationale for prevention and drug treatment as well as creating opportunities for novel drug development. This volume embraces all of these principles and should enable the reader to become rapidly updated in an area of medical importance.
*
* Focuses on aspects of disease pathogenesis that are common to a variety of lung disorders.
* Includes coverage of the mechanisms of asthma - origin, progression, and novel therapeutic interventions.
* This volume is another in the "Systems" section of the Handbook of Immunopharmacology.

Neutrophils, the most abundant white cells in humans, serve as the primary cellular defense against infection. Neutrophil Methods and Protocols, Second Edition provides a concise set of protocols written by leading researchers in the field for assessing basic neutrophil functions, investigating specialized areas in neutrophil research, and completing step diagnostic assays of common neutrophil disorders. Topics covered include an overview of neutrophils and their role in host defense and inflammation; methods most commonly used for isolating neutrophils from humans and other animal species; procedures for subcellular fractionation of human neutrophils, analysis of in vivo transmigrated neutrophils, generation of mature neutrophils from induced pluripotent stem cells and analysis of neutrophil gene expression; methods for investigating priming, oxidant production, phagocytosis, bactericidal activity and extracellular trap formation and protocols for investigating neutrophil adhesion, chemotaxis and outside-in signaling via integrins. Written in the successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and easily accessible, Neutrophil Methods and Protocols, Second Edition is a comprehensive source for detailed explanations and applications of the most modern methodological advances in neutrophil biology. Both basic scientists and clinicians will find a collection of this caliber to be an invaluable aid in their work with neutrophils.

Autoimmunity, characterized by autoreactive lymphocytes and autoantibodies, is the consequence of a failure to discriminate between self and non-self, and autoimmune diseases are an increasing threat to people living in the industrialized countries. Autoimmune disorders are treatable, but not curable, and patients can face disability at later stages of the disease. Thus, there is a medical and economic need for new concepts and treatments in autoimmune disorders. New concepts and treatments can only be achieved by an interdisciplinary approach bringing together expertise, technologies, and clinical experience. The workshop focused on multiple sclerosis, rheumatoid arthritis and type I diabetes, and discussed conventional drug therapies, gene therapy, cell and tissue transplantation therapies, and first treatments using blood stem cells for reprogramming the patients' immune system.