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.

TLR4 is one of the most important innate immunity receptors, its function mainly consisting in the activation of inflammatory pathways in response to stimulation by Pathogen-Associated Molecular Patterns (PAMPs) and Damage Associated Molecular Pattern molecules (DAMPs). This volume critically reviews the different types of TLR4 activators and inhibitors, discusses the role of molecular aggregates in agonism/antagonism as well as the pivotal role of the CD14 receptor in the modulation of TLR4 signal and the molecular details and actors of the intracellular cascade. The book presents the role of TLR4 in several pathologies, such as sepsis and septic shock caused by receptor activation by gram-negative bacterial lipopolysaccharide (LPS), in neurodegenerative and neurological diseases such as Parkinson and Alzheimer's diseases, and Amyotrophic Lateral Sclerosis (ALS). It reviews the role of TLR4 in neural stem cell-mediated neurogenesis and neuroinflammation and in Human Induced Pluripotent Stem Cells and Cerebral Organoids and discusses the emerging role of micro-RNA (miRNA) regulation by TLR4.

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.

This volume reviews the current research focused on the functional importance of unfolded protein response (UPR) signaling in the context of health and disease. The chapters present cutting-edge work describing the diverse functions of UPR signaling critical for regulating cellular and organismal physiology under physiologic and pathologic conditions. Written by internationally respected scientists, this volume is designed to provide a broad view of the diverse functional importance of UPR, and as such appeals to clinicians and academic researchers alike.

The proper physiological functioning of most eukaryotic cells requires their assembly into multi-cellular tissues that form organized organ systems. Cells of the immune system develop in bone marrow and lymphoid organs, but as the cells mature they leave these organs and circulate as single cells. Antigen receptors (TCRs) of T cells search for membrane MHC proteins that are bound to peptides derived from infectious pathogens or cellular transformations. The detection of such speci?c peptide-MHC antigens initiates T cell activation, adhesion, and immune-effectors functions. Studies of normal and transformed T cell lines and of T cells from transgenic mice led to comprehensive understanding of the mole- lar basis of antigen-receptor recognition and signaling. In spite of these remarkable genetic and biochemical advances, other key physiological mechanisms that par- cipate in sensing and decoding the immune context to induce the appropriate cellular immune responses remain unresolved. TCR recognition is tightly regulated to trigger sensitive but balanced T cell responses that result in the effective elimination of the pathogens while minimizing collateral damage to the host. The sensitivity of TCR recognition has to be properly tempered to prevent unintended activation by self-peptide-MHC complexes that cause autoimmune diseases. It is likely that once the TCR is engaged by a peptide- MHC and TCR signaling begins, additional regulatory mechanisms, involving other receptors, would increase the ?delity of the response.

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

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.

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.

The only book of its kind, Crystalline Bacterial Cell Surface Proteins assembles present-day understanding of the occurrence, structure, chemistry, genetics, assembly, function, and application potential of S-layers. The chapters are designed to stand independent of each other and provide a complete survey of the different topics in S-layer research. This book is intended to stimulate further development in basic and applied S-layer research.
Key Features
* Assembles present-day understanding of S-layers
* Provides a detailed survey of the entire field of basic and applied S-layer research
* Potential for broad application in biotechnology, vaccine development, diagnostics, molecular nanotechnology, and biomimetics

Before the arrival of penicillin in the 1940s, phage therapy was one of the few weapons doctors had against bacterial infections. It saved the life of Hollywood legend Tom Mix before being abandoned by Western science. Now, researchers and physicians are rediscovering the treatment, which pits phage viruses against their natural bacterial hosts, as a potential weapon against antibiotic-resistant infections. The Forgotten Cure traces the story of phages from Paris, where they were discovered in 1917; to Tbilisi, Georgia, where one of phage therapy's earliest proponents died at the hands of Stalin; to the Nobel podium, where prominent scientists have been recognized for breakthroughs stemming from phage research. Today, a crop of biotech startups and dedicated physicians is racing to win regulatory approval for phage therapy before superbugs exhaust the last drug in the medical arsenal. Will they clear the hurdles in time?

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...

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.

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...

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.

This volume explores the still undiscovered secrets of tumor immunology and cancer immunology by discussing the methods and techniques that world-renowned experts in the field use in their laboratories. This book provides a better understanding of the rules governing tumor and cancer immunology, and discusses innovations in the technology of the immunological "smart bullets" (monoclonal antibodies, vaccines, tumor-reactive T cells) used to specifically target cancer cells. Written in the highly 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 laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Thorough and cutting-edge, Tumor Immunology: Methods and Protocols contains a wide breadth of subject coverage that any scientist, clinician, or industry professional interested in this field will find valuable.

Untoward reactions to environmental chemicals, particularly when a subject reports difficulties with exposures to chemicals of diverse classes involving more than one organ system, have been poorly understood and an area of great controversy. Studies of airway inflammation induced by respiratory irritants have established neurogenic inflammation as the mechanism for irritant asthma and rhinitis. Remodeling of the airway after an acute irritant exposure can lead to a heightened sensitivity to irritants that persists. Recognition that rhinitis, while sometimes regarded as a trivial disease, is associated with extra-airway manifestations such as fatigue and disturbances of sleep, mood, and cognition, further elucidates how chemical exposures can be serious for susceptible individuals.
This book reviews current scientific understanding of irritant airway inflammation and related conditions, including cardiovascular effects of particulate exposures, airborne contact dermatitis and irritant dermatitis, and the brain as a target organ for both allergic and irritant reactions. It is essential reading for physicians and other healthcare workers caring for patients with environmental intolerances. Allergists, toxicologists, occupational and environmental physicians, and pulmonologists will find the materials particularly valuable. Patients and advocates for those with chemical intolerances will also find the book of interest.

The rapid progress in clinical and experimental immunological research, in addition to the radical change in immunological concepts in recent years, has been accompanied by similar developments in the technical vocabulary, and, as a consequence, frequent widespread confusion. The fourth edition of The Dictionary of Immunology will satisfy the needs of any biologist, clinician or biochemist who requires easy reference to current immunological usage.
This well-established work has been completely revised and updated to include key terms arising from new discoveries in the fast-developing fields of molecular and cellular immunology. The Dictionary of Immunology contains brief descriptions of the most commonly used immunological techniques, as well as definitions, useful in clinical immunology, of immunodeficiency states and autoimmune diseases. Clear illustrations and tables have been added to complement the text, and extensive cross-referencing is used to inform an integrated view.
The Dictionary will serve equally as a handy reference, a companion to other reference texts, or a spelling and fact checker for students, research scientists and those engaged in ancillary activities such as science journalists, and the curious lay reader.
* Special Features:
* Radical revision, including addition of 30% new terms.

The understanding how complement relates to glomerular diseases has evolved considerably during the last years. Substantial evidence has accumulated that explain how a defective or deregulated complement system results in kidney diseases. The combination and close interaction of basic research with clinical medicine has demonstrated an important role of complement effector and regulatory proteins in pathological settings of the kidney. A large panel of distinct human kidney diseases such as hemolytic uremic syndrome (HUS), membrano proliferative glomerulonephritis (MPGN), systemic lupus erythematosus (SLE) and in ischemic reperfusions injury and transplantation are caused by defective complement control. Genetic analyses have identified mutations in complement regulators that are associated with these diseases. Mutations have been identified in the fluid phase alternative pathway regulator Factor H and the membrane regulator Membrane Cofactor Protein MCP (CD46). The functional characterization of the mutant proteins allows to define the pathophysiological events on a molecular level. These new concepts and data on disease mechanisms already allowed to establish new diagnostic and novel promising therapeutic approaches for several human kidney diseases.

The name "AIDS" is an accusation. It implies punishment for sin--homosexuality and promiscuity. AIDS is a moral judgement masquerading as a scientific name, which is at the very heart of discrimination against the infected. At the bottom are drug users, victims of the War On Drugs, condemned to contract AIDS by using contaminated syringes necessitated by scarcity resulting from restrictive policies. A rational way to control HIV is to liberalize drug paraphernalia policies as in Europe. The U.S. has not taken this simple step, thus unleashing the AIDS epidemic among drug users, their sexual partners, and neonates. While this policy neglect can be understood in the context of AIDS prevention dominated by moral, political, and religious ideologies rather than epidemiological facts, there are critical racial implications. The ethnic divide separating the white researchers and the infected who belong to minorities has fuelled comparisons of AIDS with the infamous Tuskegee Syphilis Study and some preventive strategies have been called genocidal plots. Recent research indicating the ineffectiveness of bleach to disinfect paraphernalia has exposed the deadly consequences of a nonchalant attitude to research and compromises for political expediency.

The OHOLO conferences are sponsored by the Israel Institute for Biological Research and take their name from the site of the ?rst meeting on the shores of Lake Kinnereth. The purpose of these meetings is, as it was at their inception over 50 years ago, "to foster interdisciplinary communication between scientists in Israel, and to provide added stimulus by the participation of invited scientists from abroad". The core of the organizers of the OHOLO conferences are scientists from the Israel Institute for Biological Research. From time to time a particular OHOLO conference cooperates with an international scienti?c organization. The present 46th OHOLO Conference marks the resumption of the OHOLO tradition after 8 years of interruption caused by events beyond our control. It is my belief that our uncomp- mising commitment to excellence in research and development in the various areas of science in Israel is essential to our survival in this troubled region. The OHOLO conference tradition is a re?ection of this conviction. The present 46th OHOLO Conference entitled: The Challenge of Highly Pathogenic Microorganisms - Mechanisms of Virulence and Novel Medical Countermeasures intends to address the unique virulence features and ho- pathogen interactions of microorganisms constituting emerging biothreat with emphasis on Y. pestis, B. anthracis, F. tularensis and Orthopox viruses. Accordingly we selected classical microbiological as well as genomic, proteomic & transcr- tomic approaches towards developments of novel prophylactic and post-exposure treatment, as well as updated strategies of diagnostics and bioforensics.

Methods and Procedures for Preparing Resealed Erythrocytes: IHP Entrapment into Human Erythrocytes; A. Mosca, et al. Resealed Erythrocytes as a Tool for Basic Studies: ATP Monitoring in Human Red Blood Cells with Luciferase Introduced Intracellularly; V.M. Vitvitsky, et al. Resealed Erythrocytes as a Cellular Bioreactors: Acetaldehayde Oxidation by Aldehyde Dehydrogenase Loaded Erythrocytes; P. Ninfali, et al. Resealed Erythrocytes as Advanced Drug Delivery Systems: Erythrocytes as Carriers of New Anti-Opioid Prodrugs; S. Noel-Hocquet, et al. Site Specific Targeting of Resealed Erythrocytes: Erythrocytes as Carriers of Ricin A Chain; N. Chestier, et al. Human and Veterinary Studies Using Resealed Erythrocytes: Susceptibility of Carrier Erythrocytes to a Natural Hemolytic System; H.J. Kirch, et al. 36 additional articles. Index.

Why sex matters

Among human and nonhuman animals, the prevalence and intensity of infection typically is higher in males than females and may reflect differences in exposure as well as susceptibility to pathogens. Elevated immunity among females is a double-edged sword in which it is beneficial against infectious diseases but is detrimental in terms of increased development of autoimmune diseases.

The present book critically reviews the evolutionary origin and the functional mechanisms responsible for sexual dimorphism in response to infection. It emphasizes the value of examining responses in both males and females to improve our understanding about host-pathogen interactions in both sexes.

The contributors are experts in their specific disciplines which range from microbiology and immunology to genetics, pathology, and evolutionary biology.

The book aims at bringing insight to the treatment and management of infectious diseases; it delineates areas where knowledge is lacking and highlights future avenues of research.

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.