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 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.

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.

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.

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 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.

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 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.

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 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.

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.

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.

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.

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.

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.

"

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).

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.

In Immunotherapy for Infectious Disease, Jeffrey M. Jacobson, MD, and a panel of leading researchers review the state-of-the-art for treating various infections-particularly HIV-by manipulating the immune system's response rather than by chemical drugs. The contributors synthesize the principles of immune defense on the molecular level (monoclonal antibodies, vaccines, methods of antigen presentation, and cytokines and cytokine antagonists), as well as on the cellular and clinical levels levels as a protection against infection. The review of the current state of anti-HIV immunotherapy covers HIV-specific passive and active immunization strategies, gene therapy, and host cell-targeted approaches for treating HIV infection and restoring immune function.

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.

Diseases of the gastrointestinal tract are common. There is increasing appreciation of the importance of the immune system in the pathogenesis of a number of these diseases. This book covers basic aspects of innate and adaptive immunity in the gastrointestinal tract, oral tolerance, and cellular and molecular mechanisms of acute and chronic inflammation. Specific disease covered include bacterial infections, human immunodeficiency virus (HIV) infection, coeliac disease, and inflammatory bowel disease. Other topics include mucosal immunisation and intestinal transplantation immunology. The readership of this book includes clinicians, scientists, and students interested in the gastrointestinal tract.

Advances in biochemistry, cell biology, genome-wide mutagenesis - coupled with molecular technology, including gene microarray and transgenic and knock-out animals - have been instrumental in understanding the cellular processes and molecular pathways of self-tolerance and autoimmune diseases. The molecular definition of these pathways and processes has led to novel treatments for certain auto-immune diseases that are based on the pathogenesis of diseases rather than on broad-spectrum immunosuppression. This book reviews many of these current developments and proposes future novel approaches for understanding the pathogenesis of auto-immune diseases and designing novel therapy. This book covers three major areas of auto-immunity: the basic mechanisms of immunological tolerance, pathogenesis of auto-immune diseases, and some novel therapies. This book should be useful for immunologists, molecular biologists, rheumatologists, and clinical scientists.