This second edition expands upon and updates the vital research covered in its predecessor, by presenting state-of-the-art multidisciplinary and systems-oriented approaches to complex diseases arising from and driven by the acute inflammatory response. The chapters in this volume provide an introduction to different types of computational modeling, and how these methods can be applied to specific inflammatory diseases, with a focus on providing readers a roadmap for integrating advanced mathematical and computational techniques with traditional experimental methods. In this second edition, we cover both well-established and emerging modeling methods, especially state-of-the-art machine learning approaches and the integration of data-driven and mechanistic modeling. This volume introduces the concept of Model-based Precision Medicine as an alternative approach to the current view of Precision Medicine, based on leveraging mechanistic computational modeling to decrease cost while increasing the information value of the data being obtained. By presenting the role of computational modeling as an integrated component of the research process, Complex Systems and Computational Biology Approaches to Acute Inflammation: A Framework for Model-based Precision Medicine offers a window into the recent past, the present, and the future of computationally-augmented biomedical research.

Viral Vaccines Joseph L. Melnick As with history in general, the history of vaccines needs to be reexamined and updated. My task is to look back to see what has been successful and to look forward to see what remains to be accomplished in the prevention of viral diseases by vaccines. Also, I shall refer to the pertinent material discussed at two recent conferences of the Institute of Medicine, National Academy of Sciences, on virus vaccines under development and their target populations in the United States (1985b) and in developing countries (1986). These reports, plus a third on Vaccine Supply and Innovation (1985a), should be required reading for all those in both the public and the private sector who have a responsibility or interest in vaccines for the prevention of human disease. It has been through the development and use of vaccines that many viral diseases have been brought under control. The vaccines consist either of infectious living attenu ated viruses or of noninfectious killed viruses or subviral antigens. When we look at the record, it is the live vaccines that have given the great successes in controlling diseases around the world. Examples are smallpox, yellow fever, poliomyelitis, measles, mumps, and rubella."

This thesis describes the use of biophysical and biochemical methods to prove that calcium has a positive feedback effect on amplifying and sustaining CD3 phosphorylation and should enhance T-cell sensitivity to foreign antigens. The study presented shows that calcium can regulate the signal pathway in cells not only as a secondary messenger but also through direct interactions with the phospholipid bilayer. The approach used in the thesis also represents an important advance, as it couples the use of nuclear magnetic resonance (NMR) to the analysis of signaling phenomena in living cells. Moreover, the thesis optimizes the Nanodisc assembly protocol, which can broaden its range of applications in membrane protein studies. A preliminary study on the structure of dengue virus NS2B-NS3p in complex with aprotinin, which may help to develop new drugs against the dengue virus, is also included.

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.

The human immune system is a complex network of tissues and organs dispersed throughout the body. Immunology, as one of the most rapidly evolving fields in bio-medical research, has to date covered the essential cellular and molecular events neces-sary for immune responses to occur. However, it has paid relatively little attention to important developmental processes underlying the formation of the tissues themselves that carry out immune responses in humans and other mammalians. In contrast to the thymus and bone marrow that are the sole tissues for generating mature leukocytes for antigen recognition and han-dling in humans and most mammalian species, the peripheral lymphoid tissues where adaptive immune responses are focused display broad tissue distribution and possess diverse archi-tectural characteristics. These organs develop prior to the individual s exposure to external antigens, and despite their similar functions, their varied appearances indicate a substantial complexity of tissue ontogeny. This volume presents a comprehensive overview of the developmental features of the major peripheral lymphoid organs, thus examining the connection between immunological functionality and structural characteristics utilizing a developmental approach, for an audience ranging from undergraduate students to senior researchers in immunology, histology and clinical medicine."

"Complement Systems: Methods and Protocols"is composed of32 individual chapters that describe a variety of protocols to purify and analyze the activity of the individual complement components or pathways. It includes assays that describe detection of complement SNPs, clinical methods to evaluate complement system activation and data interpretation.Written in the highly successful"Methods in Molecular Biology "series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls.

Authoritative and practical, "Complement Systems: Methods and Protocols"provides acollection of well-established classical assays and recently developed new assays to analyze the complement system activation will be useful to a wide audience of scientists."

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 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.

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.

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.

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.

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.

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.

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.

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."

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.

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.

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.

Analysis by In Situ Hybridization of Cytokine mRNAS Expression in Thymic Nurse Cells.- Genetic Expression of the C-CBL Proto-Oncogene in Human Thymocytes.- Production and Selection of B Lymphocytes in Bone Marrow: Lymphostromal Interactions and Apoptosis in Normal, Mutant and Transgenic Mice.- Thymic Neuroendocrine Self Peptides and T Cell Selection.- Human Fetal Liver Cells Differentiate into Thymocytes in Chimeric Mouse Fetal Thymus Organ Culture.- Towards Identification of Memory B Cells in Human Tonsils.- Prolonged IL-4 Treatment Decreases the TNP-Specific Memory Formation for IgG1.- Selection of Anti-Arsonate Idiotype (CRIA) in A/J Mice by the Immune Network.- The Life History and Functional Roles of Accessory Cells.- The Role of Macrophages in Regeneration of Splenic Tissue after Autologous Transplantation in Rat.- In Vivo Antigen Presentation Capacity of Dendritic Cells from Oral Mucosa and Skin Draining Lymph Nodes.- Liposome Mediated Modulation of Macrophage Functions.- In Vivo gp39-CD40 Interactions Occur in the Non-Follicular Compartments of the Spleen and Are Essential for Thymus Dependent Antibody Responses and Germinal Center Formation.- The Role of Dendritic Cells in the Uptake and Presentation of Oral Antigens.- Blockage of Thymic Medullary Epithelial Cell Activation: In Vivo Consequences.- Half-Lives of Antigen/MHC Class II Complexes Differ between Distinct Organ Microenvironments.- Regulation of Neural and Peripheral Cytokine Production by Benzodiazepines and Endogenous Anxiogenic Peptides.- Could ACTH be of Prime Importance in Rapidly Altering the Thymocyte Composition in the Thymus?.- Adrenergic and Cholinergic Regulation of Apoptosis and Differentiation of Thymic Lymphocytes.- Autoimmune lpr and gld Mice: Models of Abnormal Adhesion Molecule Regulation and Defective Lymphocyte Traffic.- Vascular Addressin Expression in Peyer's Patches: An in Vivo Study of Site-Associated Regulation.- Domain 5 of the Intercellular Adhesion Molecule-1 (ICAM-1) Is Involved in Adhesion of B-Cells and Follicular Dendritic Cells.- Modifications of the Expression of Homing and Adhesion Molecules in Infiltrated Islets of Langerhans in Nod Mice.- Characterization of Giant Perivascular Spaces in the Thymus of the Nonobese Diabetic Mouse.- Adhesion Molecule PECAM-1/CD31 Is Expressed on Defined Subsets of Murine LAK Cells.- Intrathymic Gap Junction-Mediated Communication.- Complement and Antibody Enhance Binding and Uptake of HIV-1 by Bone Marrow Cells.- Follicular Dendritic Cells (FDC) Are Not Productively Infected with HIV-1 in Vivo.- Lymph Node Pathology in Experimental FIV Infection.- Lymphocyte Lifespan in Murine Retrovirus-Induced Immunodeficiency.- Analysis of HIV Infections in Human Macrophage-Like Cell Lines.- The Pivotal Role of the Immunoglobulin Receptor of Tumor Cells from B Cell Lymphomas of Mucosa Associated Lymphoid Tissue (MALT).- TNF?- Is Involved in the Mechanism of Murine Thymic Lymphoma Prevention by Bone Marrow Grafting.- Analysis of Germinal Centres in the Immune Response to Oxazolone.- Cytokine Responsiveness of Germinal Center B Cells.- The Differences in Survival and Phenotype between Centroblasts and Centrocytes.- In Vivo Localisation Patterns and Cell-Cell Interactions of Cytokine Producing T-Cells and Specific Antibody Forming B-Cells.- DHEAS Enhances Germinal Center Responses in Old Mice.- Cellular Origin of Follicular Dendritic Cells.- Germinal Centers Develop at Predilicted Sites in the Chicken Spleen.- Expression and Function of DRC-1 Antigen.- The Appendix Functions as a Mammalian Bursal Equivalent in the Developing Rabbit.- Development of Components of the Mucosal Immune System in SCID Recipient Mice.- Many Newly Formed T Lymphocytes Leave the Small Intestinal Mucosa via Lymphatics.- Analysis of IgA-Producing Hybridomas Derived from Peritoneal Bl Cells.- Modulation of the Neonatal IgA Response to Enteric Antigens by Maternal Antibody.- Antibody-Forming Cells (AFCs) in the Lung Lymphoid Tissue afte...