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.

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.

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.

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.

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 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.

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."

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."

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.

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.

Medicine has entered a golden age in which therapeutic agents are becoming widely available due to advances in basic science and technology. As such, many drugs have been developed that target inflammatory processes and/or the immune system. This book is intended for health professionals examining the modulation of inflammation by immunotherapeutic drugs. The immune system fills the primordial role of host defense and resistance to infections with pathogenic microorganisms. Several hematopoietic-derived cells constituting the innate and adaptive immune systems cooperate to provide barriers for microbial colonization and/or promote pathogen destruction within the host. Conversely, many immune cells are also involved in the pathogenesis and propagation of chronic inflammatory diseases. The beginning of this book details various components of the immune system including the cell types, lymphoid tissues, soluble cytokines and surface molecules that are essential for host defense. Breakdowns in immune tolerance, or dysregulated immune responses to antigens derived from self tissues or innocuous sources, can lead to the development of autoimmunity or chronic inflammatory diseases. Pathophysiologic roles for the immune system are detailed in corresponding chapters on autoimmunity, epithelial surfaces (lungs, skin, intestine), and transplantation, with special emphasis placed on immunotherapeutic drug targets. The last section of the book focuses on treatments that stimulate our immune system to specifically target and fight infectious diseases and cancer. In each chapter, the medications used to treat various diseases/conditions in terms of their mechanism of action and other pharmacologic properties are detailed. Chapters begin with a table showing drug names and classifications. The importance of basic science and clinical trials cannot be understated in the context of drug development. As such, the discovery of certain medications that had a lasting impact in medicine and pharmacy are highlighted in chapter subsections named "Bench to Bedside." Several clinical applications of immunotherapeutic drugs are described within end-of -chapter case studies including practice questions. The Pharmacology of Immunotherapeutic Drugs is a reference for immunologists and clinicians (medical doctors, pharmacists, nurses) examining the modulation of inflammatory processes by a variety of medications targeting the cells and mediators of our immune system.

This new edition continues to illustrate the power of biological data in knowledge discovery. It describes biological data types and representations with examples for creating a workflow in bioinformation discovery. The concepts in knowledge discovery from data are illustrated using line diagrams. The principles and concepts in knowledge discovery are used for the development of prediction models for simulations of biological reactions and events. Advanced topics in molecular evolution and cellular & molecular biology are addressed using bioinformation gleaned through discovery. Each chapter contains approximately 10 exercises for practice. This will help students to expand their problem solving skills in Bioinformation Discovery. In this new edition, there are three new chapters covering single nucleotide polymorphism, genes, proteins and disease, and protein functions driven by surface electrostatics.

This volume sets out to consider a range of cardiac diseases for which drugs may play a therapeutic role by virtue of their effects on aspects of the immune system. The book reviews diseases of the heart which may involve an immunopharmacological component, and methods and techniques for the study of physiological and biochemical functions in the heart. An important focus is the immunopharmacology of the coronary vascular endothelium and the role of cellular and biochemical components of the immune system in the pathogenesis of atherosclerosis. The content also includes a review of the use of immunologically relevant agents in the setting of cardiac transplantation from aclinical perspective. Immunotherapy has a definite role to play in cardiology to a greater or lesser extent than other forms of intervention, depending on the type of cardiac disease. Immunopharmacology of the Heart aims to identify and clarify this role and points to potential developments of the future. Immunopharmacology of the Heart is a volume for the SYSTEMS theme of The Handbook of Pharmacology. In common with all other volumes it contains standardized illustrations and terms/abbreviations (glossaries of illustrations and terms published at the back of the volume). Other topics covered include: Leukocytes and their role in ischaemic heart disease. Complement activation. Sudden cardiac death. The stunned myocardium and reperfusion injury.

This volume reviews the current state of research on immune checkpoints and offers novel concepts. It discusses the two most important immune checkpoints: T lymphocyte-associated antigen-4 (CTLA-4) and programmed cell death-1 (PD-1). It shows that antagonistic antibodies against these two molecules are highly effective in the treatment of various cancers and that PD-1 and CTLA-4 have been linked to the suppression of T-cell receptor signaling and co-stimulatory molecules. Further, the volume examines other agents, a number of cells, receptors and signaling molecules, that are also involved in the regulation of T-cell activation and extends the concept of immune checkpoints to "molecules and cells that negatively regulate T-cell activation". Playing essential roles in immune homeostasis, they could offer new targets for cancer immunotherapy, and for the therapy of autoimmune diseases. Written by internationally respected scientists, this book will appeal to basic scientists, clinicians, drug development researchers, and advanced students alike.

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.

This book provides a comprehensive overview of the cascade of events activated in the body following the implant of biomaterials and devices. It is one of the first books to shed light on the role of the host immune response on therapeutic efficacy, and reviews the state-of-the-art for both basic science and medical applications. The text examines advantages and disadvantages of the use of synthetic versus natural biomaterials. Particular emphasis is placed on the role of biomimicry in the development of smart strategies able to modulate infiltrating immune cells, thus reducing side effects (such as acute and chronic inflammation, fibrosis and/or implant rejection) and improving the therapeutic outcome (healing, tissue restoration). Current cutting-edge approaches in tissue engineering, regenerative medicine, and nanomedicine offer the latest insights into the role immunomodulation in improving tolerance during tissue transplant in the treatment of orthopaedic, pancreatic, and hepatic diseases. "Immune Response to Implanted Materials and Devices" is intended for an audience of graduate students and professional researchers in both academia and industry interested in the development of smart strategies, which are able to exploit the self-healing properties of the body and achieve functional tissue restoration.

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

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.

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.

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.

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.

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.

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.