In the summer of 1629, John Winthrop described a series of epidemics that devastated Native American populations along the eastern seaboard of New England as a "miraculous plague." Winthrop was struck by the providential nature of these waves of disease, which contributed neatly to the settlers' justifications for colonial expansion. Taking Winthrop's phrase as its cornerstone, Miraculous Plagues reimagines New England's literary history by tracing seventeenth- and early eighteenth-century epidemics alongside events including early migration, the Antinomian controversy, the evolution of the halfway covenant and jeremiad, and Boston's 1721 inoculation controversy. Moving beyond familiar histories of New World epidemics (often referred to as the "virgin soil" model), Cristobal Silva identifies epidemiology as a generic category with specialized forms and conventions. Epidemiology functions as both subject and method in Silva's argument, as he details narratives that represent modes of infection, population distribution, and immunity. He considers how regional and generational patterns of illness affected the perception of communal identity, and he analyzes the translation of epidemic events into narrative and generic terms, providing scholars a new way to conceptualize the relationship between immunology and ideology. Closing with a discussion of the HIV/AIDS epidemic, Miraculous Plagues underscores the portability of its insights into the geopolitics of medicine. Just as epidemiology aided in transforming colonial America, it continues to influence questions of geography, community, and identity that are bound up in global health practices today.

This volume provides a set of reviews dedicated to the biology of Interleukin (IL)-10. It includes chapters on its importance for maintaining immune homeostasis in humans, its role in intestinal immunity and its functions during viral and bacterial infections. In addition, it presents reviews on the mechanisms linking innate microbial recognition to the production of IL-10 and on how IL-10 recognition by its receptor functions. The roles of T and B cells as relevant sources of IL-10 are also discussed, with an emphasis on the clinical opportunities offered by IL-10-producing Tr1 cells for the suppression of unwanted immunity. Finally, the functions of other cytokines of the IL-10 family are presented. Collectively, these articles provide a comprehensive overview of our current knowledge on one of the most important anti-inflammatory cytokines known to date.

This book discusses recent developments in several laboratories studying leishmaniasis. Sequencing of the human genome, as well as of the leishmania genome, has led to significant advances in our understanding of host-immune responses against leishmania, and mechanisms of infection-induced pathology, which is responsible for morbidity and mortality. Pathogenesis of Leishmaniasis focuses on the latest basic research into leishmaniasis, but also addresses how advances in understanding can be applied to prevention, control and treatment of what the WHO has classified a neglected tropical disease.

The availability of powerful genome-wide association study technology, during the last five years, has shown that most of the "new" MS susceptibility loci are immune-response genes. It is clear that there is much novelty in the field of MS immunology, which has served as an impetus to invest in new therapies. Notably, most if not all of these are immunotherapies. Even the equally exciting field of cell-based therapies and neuro-regeneration may well rely on cells or growth factors that are no less immunomodulators than restorative of myelin and neural cell function. Multiple Sclerosis Immunology looks at MS immunology as the basis for the present and-even more-the future of treatments for this complex autoimmune condition. Both editors are immunologists, as well as clinical neurologists, and appreciate the importance of a sustained dialogue between basic and clinical scientists to ensure that "translation" is real and not just virtual.

Streptococci are Gram-positive bacteria that cause a wide spectrum of diseases, such as pharyngitis, necrotizing fasciitis and streptococcal toxic shock syndrome, as well as rheumatic fever and rheumatic heart disease as sequelae. Antibiotics alone have not been able to control the disease and in spite of many efforts an effective vaccine is not yet available. A prerequisite for novel and successful strategies for combating these bacteria is a complete understanding of the highly complex pathogenic mechanisms involved, which are analyzed in this volume. In ten chapters, prominent authors cover various aspects including streptococcal diseases and global burden, epidemiology, adaptation and transmission, and molecular mechanisms of different diseases, as well as sequelae, vaccine development and clinical management. This book will serve as a valuable reference work for scientists, students, clinicians and public health workers and provide new approaches to meeting the challenge of streptococcal diseases.

This volume covers all aspects of infection by pathogenic Leptospira species, the causative agents of the world's most widespread zoonosis. Topics include aspects of human and animal leptospirosis as well as detailed analyses of our current knowledge of leptospiral structure and physiology, epidemiology, pathogenesis, genomics, immunity and vaccines. Updates are presented on leptospiral systematics, identification and diagnostics, as well as practical information on culture of Leptospira. Contact information is also provided for Leptospira reference centers. All chapters were written by experts in the field, providing an invaluable reference source for scientists, veterinarians, clinicians and all others with an interest in leptospirosis.

DNA Vaccines: Methods and Protocols, Third Edition explores innovative approaches and technologies used to design, deliver, and enhance the efficacy of DNA vaccines. Featuring applications which should be of great value in moving vaccines from research to clinic, this detailed volume includes sections on DNA vaccine design and enhancement, delivery systems, production, purification, and quality, as well as chapters on new vaccine applications. Written in the highly successful Methods in Molecular Biology series format, chapters contain introductions 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. Authoritative and practical, DNA Vaccines: Methods and Protocols, Third Edition serves the important role of further documenting the potential of the DNA vaccination as a platform technology for treatment and prevention of human disease.

Smoking and Lung Inflammation is the first book directly related to chronic lung inflammation of its kind in several respects. First, the it focuses on both basic and clinical research on COPD, and the inflammatory mechanisms that function in these diseases. Second, it is unique with respect to scope of the discussion of the unusual characteristics of the immune response which occurs in these patients. Third, it includes knowledge being gained from translational research conducted through clinical trials at several Medical Schools in the United States. Not only is this research providing information about novel drugs and therapies, but it is also advancing our understanding of the genetics of these diseases. This work will illuminate the molecular basis for these diseases, and hopefully will permit us to individualize the therapies for these diseases.

In Eosinophil: Methods and Protocols, experts in the field of eosinophil biology comprehensively provide detailed methodological insight into the study of this fascinating cell. This book is aimed at a diverse range of basic and clinical scientists who wish to work with eosinophils or who require an update of their knowledge or to gain the information required to study a function of the eosinophil different to their current area of enquiry. 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 key tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Eosinophil: Methods and Protocols seeks to aid scientist in the discovery of new hypotheses and for further examination of this intriguing cell.

Virus-Host Interactions: Methods and Protocols covers various aspects of virological research, such as biochemical approaches, including molecular interactions and regulatory mechanisms on the protein as well as the RNA level with a strong focus on the manifold possibilities to study protein-protein interactions, as well as cell biological and immunological methodologies. Viruses represent a reduced form of life that depends on host cells for propagation. To this end, viruses approach and penetrate cells and usurp cellular machineries for their own benefit. Recent technological improvements have enabled the systematic analysis of the virus-host interplay be it on the genomic, the transcriptomic, or proteomic level. In parallel, bioinformatic tools have emerged in support of the large datasets generated by these high-throughput approaches. 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, Virus-Host Interactions: Methods and Protocols will prove invaluable to professionals and novices with its well-honed methodologies and protocols.

Digenetic trematodes constitute a major helminth group that parasitize humans and animals, and are a major cause of morbidity and mortality. The diseases caused by trematodes have been neglected for years, especially as compared with other parasitic diseases. However, the geographical limits and the populations at risk are currently expanding and changing in relation to factors such as growing international markets, improved transportation systems, and demographic changes. This has led to a growing international interest in trematode infections, although factors such as the difficulties entailed in the diagnosis, the complexity of human and agricultural practices, the lack of assessments of the economic costs or the limited number of effective drugs are preventing the development of control measures of these diseases in humans and livestock. In-depth studies are needed to clarify the current epidemiology of these helminth infections and to identify new and specific targets for both effective diagnosis and treatments. The main goal of this book is to present the major trematodes and their corresponding diseases in the framework of modern parasitology, considering matters such as the application of novel techniques and analysis of data in the context of host-parasite interactions and to show applications of new techniques and concepts for the studies on digenetic trematodes. This is an ideal book for parasitologists, microbiologists, zoologists, immunologists, professional of public health workers, clinicians and graduate and post-graduate students.

This comprehensive volume compiles the concepts essential for the understanding of the pharmaceutical science and technology associated with the delivery of subunit vaccines. Twenty-one chapters are divided into four main parts: (I) Background; (2) Delivery Systems for Subunit Vaccines; (3) Delivery Routes, Devices and Dosage Forms; and (4) Pharmaceutical Analysis and Quality Control of Vaccines. Part one provide a basic background with respect to immunology and general vaccine classification. In part two, it presents representative types of vaccine delivery systems individually with focus on the physicochemical properties of the systems and their significance for the immune response they stimulate. These delivery systems include aluminum adjuvants, emulsions, liposomes, bilosomes, cubosomes/hexosomes, ISCOMs, virus-like particles, polymeric nano- and microparticles, gels, implants and cell-based delivery systems. Following these chapters, part three addresses the challenges associated with vaccine delivery via specific routes of administration-in particular subcutaneous, intramuscular, oral, nasal, pulmonary, transdermal and vaginal administration. Furthermore, the specific administration routes are discussed in combination with device technologies relevant for the respective routes as well as dosage forms appropriate for the device technology. Finally, the fourth part concerns pharmaceutical analysis and quality control of subunit vaccines.

Primary Sjoegren's syndrome is a rheumatic disease affecting around 0.1-0.2% of the adult female population and can result in significant disability without adequate therapy. Diagnosis is often delayed and suggested therapies may not be optimal, and a multidisciplinary approach that includes rheumatologists, ophthalmologists, oral medicine physicians, and others is important to patient management. This volume summarises current understanding of the pathogenesis of the disease, including advances in the genetics of Sjoegren's syndrome. Chapters cover disease mechanisms, clinical diagnosis and assessment, secondary Sjoegren's syndrome, the role of laboratory investigations, and imaging. A therapy-based section covers topical oral and ocular therapies, and the role of steroids and biologics are also addressed. Sjoegren's Syndrome is a practical concise pocketbook featuring key points and illustrations showing important mechanisms of disease and pathways of care. The book will be of interest to trainees in rheumatology, ophthalmology, and oral medicine/surgery; specialist practitioners and therapists involved in the care of patients with Sjoegren's syndrome; and primary care physicians, dentists, and other specialists such as ENT physicians.

This book explores the many mechanisms by which the most prevalent Spirochetal pathogens persist in a healthy immune-competent host. Among them are the direct and indirect suppression of host immune signals, phase and antigenic variation, escaping recognition by host complement proteins, and seclusion into immune privileged sites. We also explore antibiotic therapy for control of infection, a baffling topic that lends itself to exalted interpretation.

This volume gathers the leading research on antibody-drug conjugates and immunotoxins. Following a rigorous overview, the volume delves into focused sections on all aspects of ADCs and ITs from clinical development through to targeted therapeutic applications and the latest technologies.

The knowledge of Th17 cells and other cell populations which secrete IL-17A, and/or IL-22 has expanded tremendously since the publication of the first edition "Th17 Cells: Role in Inflammation and Autoimmune Disease" in 2008. The present volume has been completely revised with the addition of new chapters on the IL-17 receptor family and signaling, and an in-depth review of IL-22 and innate lymphoid cells. The differentiation of naive T cells into regulatory T cells and Th17 cells as well as the plasticity of Th17 cells is discussed. The role of IL-22 in cutaneous inflammation including psoriasis has been reviewed. In addition, the volume contains critical updates on autoimmunity, organ transplantation, tumor immunology and genetic mouse models for mechanistic studies. Lastly, the latest clinical progress in neutralizing antibodies to IL-17A, IL-17RA not only confirms the therapeutic promise foreseen in 2008, but also improves our knowledge of the pathogenesis of autoimmune diseases. In summary, this is a timely update and important review of the clinical and experimental aspects of IL-17, IL-22 and their producing cells.

Infectious Diseases: Selected Entries from the Encyclopedia of Sustainability Science and Technology presents authoritative, peer-reviewed contributions from leading experts on a wide range of major infectious diseases of global importance. Infectious diseases account for more than 17 million deaths each year worldwide. While modern medicine and technology have diminished the threat of many of these pathogens in high-income countries, the ever present threats of re-emerging infections, population mobility, natural disasters, and pathogen genetic variability are but some of the reasons for the dynamic threat of this broad category of risks to human health. An indispensable resource for students and scientists, the volume also covers some of the new technologies currently under development for infectious disease prevention, treatment, and eradication. The greater part of the infectious disease burden remains in the tropics, where low and middle-income countries lack the resources, infrastructure, and health systems to mount or sustain control efforts. Many contributions describe the efforts of the scientific research community and international donor agencies to achieve the integrated goals of vigilant surveillance, improved and cost-effective diagnostics, and treatment for sustainable disease control.

The book starts with an introduction to and history of myeloid-derived suppressor cells (MDSCs), followed by a description of their differentiation, their role in the tumour microenvironment and their therapeutic targeting. It closes with an outlook on future developments. In cancer patients, myelopoiesis is perturbed and instead of generating immunogenic myeloid cells (such as dendritic cells, inflammatory macrophages and granulocytes), there is an increase in highly immature MDSCs. These cells are distributed systemically, resulting in general immunosuppression. They also infiltrate tumours, promoting their progression and metastasis by inhibiting the natural anti-tumour immune response. As these cells also interact with classical anti-neoplastic treatments, they have become major therapeutic targets in the pharmaceutical industry and in oncology research.

This volume focuses on various aspects of interleukin-27 (IL-27), especially its potential for clinical applications. The authors discuss the downstream signaling from the IL-27 receptor and its molecular targets in immune cells including Th1, Th2, Th17, Treg, Tr1, Tfh, B cells, DCs and macrophages. The inhibition of Th17 cells by IL-27 is vital for the maintenance of the feto-maternal tolerance and the prevention of lupus, multiple sclerosis, autoimmune uveitis, immune thrombocytopenia and atherosclerosis. However, the same inhibitory capabilities compromise the immune response to bacterial pathogens, and IL-27 is a pathogenic factor in sepsis and tuberculosis. Also covered are the conflicting reports on the role of IL-27 in rheumatoid arthritis, the effect of IL-27 on epithelia, which seems to play a role in asthma, psoriasis and inflammatory bowel diseases, and the direct cytotoxic and anti-vascular effects of IL-27, which make it a promising agent for the treatment of cancer. Accordingly, this volume will be of interest to researchers and clinicians alike.

Development of new-generation vaccines is now more challenging than ever, as identifying, purifying and evaluating vaccine antigens is a complex undertaking. Most importantly, once the relevant antigens have been identified, key focus then shifts to the development of suitable delivery systems and formulations to achieve maximum in vivo potency with minimum potential side effects. These novel formulations-many of which will be nanoparticulates-can deliver the antigens to the desired site, to the relevant antigen presenting cells, and prevent systemic exposure of the immune potentiators. The proposed book will outline all the critical steps that need to be considered for successful development of various types of nanoparticulate delivery systems for vaccine antigens. These contributions from leading experts in the area of vaccine formulation and delivery systems will tie in what is the most current status, including clinical evaluations with these novel vaccine technologies.

This volume will address an important emergent area within the field of immunomics: the discovery of antigens and adjuvants within the context of reverse vaccinology. Conventional approaches to vaccine design and development requires pathogens to be cultivated in the laboratory and the immunogenic molecules within them to be identifiable. Conventional vaccinology is no longer universally successful, particularly for recalcitrant pathogens. By using genomic information we can study vaccine development in silico: 'reverse vaccinology', can identify candidate subunits vaccines by identifying antigenic proteins and by using equally rational approaches to identify novel immune response-enhancing adjuvants.

The concept of using bispecific antibodies for cancer therapy by retargeting immune effector cells was developed several years ago. Initial clinical studies were rather disappointing mainly due to low efficacy, severe side effects and the immunogenicity of the bispecific antibodies. The progress in antibody engineering finally led to the generation of new classes of bispecific antibodies lacking these obstacles. In addition, new applications were established, such as pre-targeting strategies in radioimmunotherapy and dual targeting approaches in order to improve binding, selectivity and efficacy. In this book, the different ways of generating bispecific antibodies are described, with emphasis on recombinant formats. The various applications of bispecific antibodies, e.g. in cellular cancer immunotherapy, radioimmunotherapy and pretargeting strategies are covered, and emerging applications such as dual targeting strategies, which involve the simultaneous inhibition of two targets, are addressed.

Fungi are eukaryotic microorganisms that are closely related to humans at cellular level. Human fungal pathogens belong to various classes of fungi, mainly zygo- cetes, ascomycetes, basidiomycetes, and deuteromycetes. In recent years, fungal infections have dramatically increased as a result of improved diagnosis, high frequency of catheterization, instrumentation, etc. However, the main cause remains the increasing number of immunosuppressed patients, mostly because of HIV infection and indiscriminate usage of antineoplastic and immunosuppressive agents, broad-spectrum antibiotics and prosthetic devices, and grafts in clinical settings. Presently available means of combating fungal infections are still weak and clumsy compared to control of bacterial infection. The present scenario of antifungal therapy is still based on two classes of antifungal drugs (polyenes and azoles). These drugs are effective in many cases, but display toxicity and limited spectrum of ef?cacy. The recent trend towards emergence of drug-resistant isolates in the clinic is an additional problem. In recent years, a few new antifungal drugs have entered the clinics, but they are expected to undergo same fate as the older antifungal drugs. The application of fungal genomics offers an unparalleled opportunity to develop novel antifungal drugs. However, it is too early to expect any novel drugs, as the antifungal drug discovery program is in the stage of infancy. Interestingly, several novel antifungal drug targets have been identi?ed and validated.

Challenging Cases in Rheumatology and Diseases of the Immune System is the latest title in a growing collection of thought-provoking case-based titles from Massoud Mahmoudi, D.O., Ph.D. Like his three preceding titles, Challenging Cases in Allergy and Immunology (2009), Challenging Cases in Allergic and Immunologic Diseases of the Skin (2010), and Challenging Cases in Pulmonology (2011), this easy-to-read title presents the topic in a challenging and enjoyable case-based format. Developed by 30 distinguished contributors, the book consists of six parts and 16 chapters, with each chapter presenting two cases. The style of this title follows the previous books: each topic begins with an abstract, followed by a case presentation, working diagnosis, data, final diagnosis, and discussion. In addition, to enhance a review of the subject and stimulate critical thinking, there are 5 to 10 multiple choice questions and answers in each chapter. Challenging Cases in Rheumatology and Diseases of the Immune System is an indispensable resource for all clinicians who care for patients with rheumatic and immunologic disorders.

A Key Regulator of Postnatal Skeletal Remodeling.- Ectodomain Shedding of Receptor Activator of NF-KB Ligand.- The Negative Role Of Ids In Osteoclastogenesis.- Functional Genetic and Genomic Analysis of Modeled Arthritis.- Dexamethsone Suppresses Bone Formation via the Osteoclast.- Immunologic Regulation Of Bone Development.- Pth Regulates The Hematopoietic Stem Cell Niche In Bone.- Regulation Of Hematopoietic Stem Cells In The Osteoblastic Niche.- The Chemokine Cxcl12 And Regulation Of Hsc And Lymphocyte Development In The Bone Marrow Niche.- Osteoclast Precursor Cells.- Interaction with estrogen receptors as treatment of arthritis and osteoporosis.- Novel Signaling Pathways And Therapeutic Targets In Osteoclasts.- The Enigmatic Function of TREM-2 in Osteoclastogenesis.- Role of cell-matrix interactions in osteoclast differentiation.- Positive and negative roles of IL-6, STAT3 and SOCS3 in inflammatory arthritis.- Control of Osteoclast activity and bone loss by IKK subunits: new targets for therapy.- Targeting Osteoporosis And Rheumatoid Arthritis By Active Vaccination Against Rankl.- RANKL Inhibition: From Mice to Men (and Women).