Signal transduction through leukocyte receptors involves a variety of signaling molecules including kinases, phosphatases, adaptor proteins, small GTPases GTP exchange factors, membrane phospholipids as well as others. These signal transducers, regulated by inter- and intra-molecular interactions, as well as by various post-translational modifications, lead to the activation of transcription factors that mediate cellular differentiation and growth, effector cell functions, and apoptotic cell death. Several investigators from various parts of the world convened at the 3rd Lymphocyte Signal Transduction Workshop in Crete, Greece from May 27 to June 1, 2005 to discuss their most recent findings in leukocyte signaling. This volume represents a collection of topics discussed during the conference.

Contents. List of Contributors. Preface. T.J. Mitchell and T.J. Williams: The role of eotaxin and related CC-chemokines in asthma and allergy. Roger J. Davis: Signal transduction by the JNK group of MAP kinases. Marie Chabot-Fletcher: TNF and IL-1 signaling to NF-kB. Anthony M. Manning: Small molecule regulators of AP-1 and NF-kB. Robert T. Abraham: Mammalian target of rapamycin: Immunosuppressive drugs offer new insights into cell growth regulation. Catherine A. Burton, John Boylan, Candy Robinson, Janet Kerr and Pamela Benfield: Constitutive expression of a tumor suppressor leads to tumor regression in a xenograft model. Steven D. Shapiro: Macrophage metalloproteinases in destructive inflammatory diseases. Nancy H. Ruddle: Lymphotoxin in inflammation and lymphoid organ development: Variations on a theme. Steven L. Kunkel, Sem H. Phan, Nicholas W. Lukacs, Cory Hogaboam and Stephen W. Chensue: Chemokine/cytokine biology during the evolution of fibrotic disease. Long Gu, Susan C. Tseng and Barrett J. Rollins: The role of MCP-1 in disease. Lisa A. Beck, Cristiana Stellato, Syed Shahabuddin, Renate Nickel and Robert P. Schleimer: The role of chemokines in allergic diseases of the airways. James Winkler and Ken Tramposch (coordicators): Ninth International Conference of the Inflammation Research Association, November 1-5, 1998: Summaries of workshops and poster discussions. William Williams and Elizabeth Arner (chair persons): Targets in rheumatoid and osteoarthritis. Lawrence Wennogle and Nancy Cusack (chair persons): Signal transduction and regulation of gene expression. James Burke and Floyd Chilton (chair persons): Mediators in inflammation and their enzymes. Denis Schrier and Fandrew Issekutz (chair persons): Cell adhesion molecules and leukocyte trafficking. Robert M. Strieter and David Underwood (chair persons): Pulmonary inflammation, fibrosis, and disease. W. Hunter and E. Turley (chair persons): Angiogenesis, wound repair and skin inflammation. Index.

Toll Receptors and the Renaissance of Innate Immunity Elizabeth H. Bassett and Tina Rich Overview n the last few pages of Immunology: The Science of Self-Nonself Discrimination Jan Klein ponders on what he would study if he were to start over in the lab. ^ Dismissing the I antibody, MHC, the T-cell and parasitology, he considers instead the phylogeny of immune reactions, particularly in ancient phyla. As for a favored cell he chooses the macrophage. Describ ing it as a ^^MddchenfUr alles," (all purpose kitchen maid) Klein believed that this immunocyte still had secrets to reveal. Toll-Like Receptor (TLR) biology would prove to be one of these secrets. Analyses of the evolution of these receptors (Tolls and TLRs) have also helped us to rethink immune system phylogeny. In the first part of this chapter the history of the discovery of Toll and TLR biology is described. The evolution of the TLR genes and theories of immune function are covered in later sections. The remainder of this book presents work from nine groups active in the field. In the first chapter, "The Function of Toll-Like Receptors", Zlatko Dembic sets the stage by introducing us to many of the components of the immune system and their relationships vis a vis Toll receptors. Zlatko finishes his chapter with a discussion about current immune system models and contributes his own 'integrity model'. Work from the laboratory of Nicholas Gay follows this in "Structures and Motifs Involved in Toll Signaling".

Influenza continues to be an ongoing problem despite the existence of vaccines and drugs. Disease outbreaks can occur relatively quickly as witnessed with the recent emergence of the influenza virus A/H1N1 pandemic. The development of new anti-influenza drugs is thus a major challenge. This volume describes all aspects of the virus structure and function relevant to infection. The focus is on drug discovery of inhibitors to the enzyme sialidase, which plays a key role in the infectious lifecycle of the virus. Following an overview of the influenza virus, the haemagglutinin, the interactions with the cell receptors and the enzymology of virus sialidase, recent results in drug design are presented. These include a full coverage of the design, synthesis and evaluation of carbohydrate as well as non-carbohydrate influenza virus sialidase inhibitors. Further reviews of the clinical experience with influenza virus sialidase inhibitors and of the development of resistance to these inhibitor drugs complement the topic.

This volume provides in-depth reviews of model systems that exemplify the arms race in host-pathogen interactions. Somatic adaptations are responsible for the individualization of biological responses to the environment, and the continual struggle between host immune systems and invading pathogens has given rise to corresponding processes that produce molecular variation. Whether in mollusks or human beings, various host somatic mechanisms have evolved independently, providing responses to counter rapidly-changing pathogens. The pathways they utilize can include non-heritable changes involving RNA and post-translational modifications, or changes that produce somatic DNA recombination and mutation. For infectious organisms such as protozoans and flatworms, antigenic variation is central to their survival strategy. Evolving the ability to evade the host immune system not only increases their chances of survival but is also necessary for successful re-infection within the host population.

This book grew out ofmy interest in what is often called "the immunological paradox ofpregnancy." How is it possible that the fetus-halfofwhosegenetic apparatuscomesfrom thefather and is foreign to the mother-can survive to term? This is a question that intrigues all immunologists. For me, it has been of interest ever since I heard a lecture on the subject in medical school, long before I thought ofbecoming a "professional immunologist." Indeed, the question ofthe immunological aspect of fetal survival (or demise) should be of interest to any biologist or physician. The question becomes broader ifone considers the immunologic relations between motherand fetus, because they represent a unique symbiotic union. Whatimmunologic problemsinthemothermayaffecttheoffspring, and isitpossiblethatfetal immunology willaffectthe mother? Finally, there is the question ofwhether immunology is important in recur- rent spontaneous abortion. Every authorowes the reader a general oversightofthe book in hand, indicating the terrain to be covered, and, by inference, the territory that will not be explored. 1. This is primarily a book for clinicians. I will only men- tion animal experiments and data in passing, and as they may illuminate a clinical problem or observation. 2. The interest here is the immunology ofmaterno--fetal re- lations, once a pregnancy has begun. Therefore, I will notcover immunological aspects ofsterility, nor touch on the immunological approaches to controlling fer- tility, i.e., "contraceptive vaccines." 3. This is a book mainly concerned with pathogenesis.

Basophils and mast cells are similar but unique secretory cells with a well-documented role in immediate-hypersensitivity reactions. The presence of these cells in various cell mediated hypersensitivity reactions, in tissues of multiple diseases, and as a component of the host reaction to injury and repair in numerous circumstances is well known. Release of stored and newly generated mediators of inflammation from basophils and mast cells contributes to the cascade of pathogenetic events in circumstances under which these release reactions occur. Despite insights acquired through studies of these pathologic events, the role of basophils and mast cells and their secretory products in health is not known. In this book, I review much of the structural information regarding basophils and mast cells of multiple species. Ultrastructural studies of rat mast cells historically precede and quantitatively exceed similar studies of basophils and mast cells of other species. Therefore, I first review these background studies as an entity. Then I discuss the contents of two prominent organelles-granules and lipid bodies-in basophils and mast cells of several species. The ultrastructural morphology of basophils and mast cells in three species is presented in detail to establish appropriate guidelines for their recognition and to provide general rules for analysis which are appropriate for the identification of these cells in other species as well."

ISPP2009, the 13th International Symposium on Phototrophic Prokaryotes, was held in Montreal, Canada, from August 9 to August 14. This was only the second time that the ISPP series was in North America. ISPP2009 was well attended with about 280 registered participants from over 30 countries. A stimulating and inf- mative program showcased the recent developments in this ever-evolving eld. This is always one of my favourite conference series to attend because not only does it inform my speci c research passions, it broadly educates me in ways that improve my teaching and increase my breadth of understanding in a variety of outside areas. Indeed, the ISPP series brings together a broad spectrum of interests, techniques, and disciplines. Both established researchers and newcomers to this eld gave oral presentations in a large number (80) of plenary and parallel symposia sessions which proved to have active audience participation and lively discussions. A large number of excellent poster presentations supplemented the oral program. I think that the high quality of the scienti c presentations, as well as the enjoyable social events, was widely appreciated. Things ran very smoothly, from the original registration to the closing ceremony, thanks to Isabel Stengler and her team at IS Event Solutions.

This Methods in Molecular Biology book offers methods for studying inflammasome function, including generation of inflammasome stimuli, monitoring of caspase-1 activity and processing, activation of IL-1 cytokines, plus lab protocols, material lists and tips.

Enzyme-linked immunospot assay (ELISPOT) has been known for some time as a unique state-of-the-art technique for studying the cytokine-secreting activity of immune system cells, and it appears to be one of the fast growing applications in biomedical research, becoming an indispensable tool in vaccine development, HIV research, transplantation studies, and cancer and allergy research. The second edition of Handbook of ELISPOT: Methods and Protocols, only the second book in the field which is entirely dedicated to ELISPOT assay, shares the detailed techniques that have been developed since the release of the popular first edition. Straight from the labs of seasoned experts, this book covers setting and performing ELISPOT assays, ELISPOT for veterinary research, advanced ELISPOT techniques, image and data analysis, as well as vaccine development and diagnostics. Written in the highly successful Methods in Molecular Biology (TM) series format, chapters include introductions to their respective chapters, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, Handbook of ELISPOT: Methods and Protocols, Second Edition serves as a compilation of a technical reference and a troubleshooting guide for researchers, both experienced and novice, worldwide in order to advance the usage of this key tool.

Immunotherapy in Resistant Cancer: From the Lab Bench Work to Its Clinical Perspectives provides high level knowledge on detailed mechanisms of actions and biological interactions of different immune drugs, with an aim of offering researchers and clinicians cutting-edge therapies to overcome drug resistance. The book explains the latest immunotherapies for different types of cancer, helping users carry out research projects or create alternatives for drug development in the pharmaceutical industry. Topics discussed include the relationship between immunotherapy and macrophages, immune checkpoints in different types of cancer, immune cocktails in solid tumors, and immune-phenotyping. Additionally, the book presents basic and clinical data on immunoresistance and glycosylation. This book is a valuable source for cancer researchers, medical doctors, clinicians and members of the biomedical field who must understand certain mechanisms to fight cancer that is resistant to immunotherapy.

Matters of Sport is a tribute to Eric Dunning, the leading sports sociologist in the English-speaking world. This book addresses Dunning's contributions to the sociological and historical study of sport, covering key topics such as hooliganism, celebrity and gender relations.

A broad range of leading academics from Europe and North America reflect on the ways in which Dunning's work has influenced their own research and understanding of sport.

This volume was previously published as a special issue of the journal Sport in Society.

This book provides a systematic review of the development, function, and patho-physiologic role of plasmacytoid dendritic cells (pDCs) in humans. The chapters of the book discuss the origin and discovery, hematopoietic development as well as molecular regulation of pDCs in the context of immune activation as well as immune tolerance. It also discusses the role of pDCs in human diseases, including infections, autoimmune/inflammatory diseases, cancers and metabolic disorders, and opportunities for pDC-targeting therapies in these varied clinical contexts.

Interleukins are a family of proteins that regulate the maturation, diff- entiation, or activation of cells involved in immunity and inflammation, and belong to a broader family termed cytokines. Collectively these proteins are the key orchestrators of host defense and the response to tissue injury. There are currently 23 different interleukins (numbered from IL-1 to IL-23), although the full extent of the interleukin family will only become clear upon analysis of the human genome sequence. Most important, interleukins are central to the pathogenesis of a wide range of diseases that involve an immune com- nent, including such conditions as rheumatoid arthritis, multiple sclerosis, ulcerative colitis, psoriasis, and asthma. Interleukins have also been imp- cated in other conditions, including cancer, migraine, myocardial infarction, and depression. In essence, when cells are activated by interleukins, a program of gene expression is initiated in the target cell that alters the cell's phenotype, leading to enhanced immune reactivity, inflammation, and/or proliferation. Interleukins are therefore at the core of the cellular basis for many diseases. They are the subject of intense investigation by biomedical researchers and the targeting or use of interleukins in the clinic is proceeding apace. Approaches such as t- geting IL-4 in asthma or IL-1 in joint disease are being pursued, and it is likely that in the next 5-10 years a number of new therapies based on either inhib- ing or administering interleukins will be available.

This book provides an essential update on the startling array of novel insecticidal toxins and drugs produced by the fascinating bacterium Photorhabdus. The respective chapters describe everything from the detailed molecular biology of the 'Toxin complexes' or Tc's to the complexity of insect immune response in relation to both the bacterium and its nematode vector. The volume covers both primary (toxin production and regulation) and secondary (natural product synthesis and regulation) metabolism and emphasises the potential use of toxins and drugs in both agriculture and medicine. It also discusses in detail two totally novel quorum sensing mechanisms and the likely role of LuxR solos in sensing the presence of different bacterial hosts. Lastly, the book explores the unique case of P. asymbiotica, which seems to have evolved the ability to infect both insects and humans. This synthesis proves that Photorhabdus truly does offer a 'gold mine' for the discovery of novel insecticidal proteins and novel natural products with potential uses in agriculture and medicine alike.

Our own experience shows that there is no simple, yet of good scientific and clinical quality guide for practitioners and patients on gastrointestinal diseases. In the proposed book we will cover a vast area in the field, from GI tract physiology to disease diagnosis and treatment, in a comprehensive and approachable manner. The guide will not replace online resources (often used by patients) or specialized editions addressing experienced medical doctors, but rather fill the gap between those two. Our aim is to design this book so that it appeals to a wider audience; yet - if needed - encourages to explore the field further.

A synthesis of current concepts about the evaluation, treatment, and future directions in MS. On the evaluation side, the authors review the use of MRI, magnetic resonance spectroscopy, functional MRI, and three-dimensional MRI, and consider the rapidly developing body of pathologic information they have yielded. On the treatment side, the focus is on recently approved medications (Novantrone), new indications for medications (CHAMPS Trial), medications in development (Oral Interferon Tau, Oral Copaxone, and Oral Cellcept), immunosuppressive therapy for both progressive disease and symptomatic therapy; the current medications for treating relapsing-remitting MS (Avonex, Betaseron, and Copaxone) are also discussed. For future directions, the authors present the current best thinking, as well as the latest discoveries in immunology relating to MS, including groundbreaking B-cell research and its applications to specific immunotherapies, and the use of immune markers for tracking the disease.

The understanding of the role of dendritic cells (DCs) in immune responses has come a long way since Steinmann and colleagues described these cells in 1972. - tensive research during the intervening period has provided a good understanding of the complexity of the DC system and its pivotal role in immunity. It is also now clearer how different subsets of DCs interact and regulate each other and how DC populations affect the function of other cells of the immune system. The improved understanding of their role in immune response has led to the idea that modulation of DC functions by, for example, pharmacological agents could be used as a pot- tial therapeutic approach in some pathological conditions. The actual applicability and therapeutic potential of all these approaches is yet to be fully demonstrated but nonetheless, animal models of human diseases are proving to be very helpful in the evaluation of manipulated DCs as a new treatment in diseases like cancer, auto- munity or asthma. DCs are integral to the initiation and regulation of immune response (Banchereau et al. 2000). The outcome of antigen presentation by DCs is determined by their maturation status, which can be induced by their interaction with danger signals. To recognise a wide array of pathogen-associated molecular patterns (PAMP), DCs express a number of pattern recognition receptors (PRR) such as Toll-like rec- tors (TLRs) and C-type lectin receptors (CLR) that recognise structural components of pathogens and discriminate between self and non-self molecules.

Immune Mechanisms in Inflammatory Bowel Disease is a highly, concise update of the most recent advances in the immunobiology, genetics and microbiology related to Inflammatory Bowel Disease. This book broadly treats the topics that lead to understanding of the pathogenesis of this disease in an organized, systematic approach.

Whole new areas of immunological research are emerging from the analysis of experimental data, going beyond statistics and parameter estimation into what an applied mathematician would recognise as modelling of dynamical systems. Stochastic methods are increasingly important, because stochastic models are closer to the Brownian reality of the cellular and sub-cellular world.

W. B. Harrison, B. A. C. Dijkmans During the last decade intervention has been instituted for all kinds of disease- even in a premorbid state, as early as possible, to control the activity of the disease, to avoid further damage and to maintain quality of life. Apart from the principle 'Treat now, not later," emphasis is laid on aggressive initial therapy. These adagia have influenced in recent times all fields of medicine, from oncology to infectious diseases and also - the topic of the present edition - the "autoimmune diseases." As an example of the latter, rheumatoid arthritis (RA) demonstrates how the attitude of physicians has been changed. From an expectant point of view in the eighties (primum nil nocere) the attitude has been changed, as we approached and entered the new millennium, to initial ag gressive therapy especially in patients with a poor prognosis. Despite the advance of instituting monotherapy with a single optimised disease-modifying anti-rheumatic drug (DMARD) - with methotrexate as prototype agent in RA - adequate disease re mission is not often achieved, and adverse events may well prevent the use of higher dosages of the single agent in question. Therefore, the next step was to combine two or more DMARDs. The choice of combining DMARDs can be purely practical and based upon the anti-rheumatics most used in daily practice, for instance methotrexate and sulphasalazine. The choice of combining drugs can be influenced by different toxicity patterns to avoid cumulative toxicity."

Integrating Population Outcomes, Biological Mechanisms and Research Methods in the Study of Human Milk and Lactation is the product of the 10th Conference of the International Society for Research on Human Milk and Lactation, held on September 15-19, 2000, in Tucson, Arizona. The presented sessions at the meeting are as diverse as the volume itself. These sessions include the impact of micronutrient deficiencies during lactation on maternal and infant health, the premature infant, developmental immunology, breastfeeding in the industrialized world, and viral transmission in milk. Whenever possible, the sessions were organized to include human population research, research showing the biological underpinnings of the effects on human health, and important methodological issues. This volume is a contemporary and influential tool for human milk biologists, breastfeeding epidemiologists, biochemists, immunologists, clinical specialists, and all professionals and researchers in the field.

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 na ve 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.

The Third Aegean Conferences Workshop on Complement-Associated Diseases, Animal Models, and Therapeutics convened to discuss progress in complement research as it pertains to human disease pathogenesis and therapeutics. The rapid pace of research and new experimental approaches allow an integrated view of the in vivo biology of the complement system. This book collects writings on the functions of complement, pathophysiology, protein structures, design of complement inhibitors, and complement assays discussed at the conference.