Gastrointestinal diseases present a considerable problem in human medicine in terms of both morbidity and mortality. The aim of this book is to cover the different immunological disorders of the gut with special reference to immunopathological and protective mechanisms. It will be of general interest to clinicians, scientists and students concerned with the gastrointestinal tract. Topics covered include: the current status of research into toxin-secreting pathogens, Campylobacter, Giardia and HIV; the immunological features of idiopathic inflammatory gut diseases such as Crohn's disease and intractable diarrhoea; the genesis of the flat mucosa; the iatrogenic diseases of the gut such as graft-versus-host disease and small bowel allografts; the immune mechanisms and lesions in the gut of patients with parasitic nematode infections (very important in the tropics). Basic background on the immune apparatus in the intestine is also discussed, as are the effects of inflammation on intestinal permeability.

Physiological, pharmacological and molecular biological data generated over the past three decades have demonstrated the existence of two major families of extracellular receptors, the P1, a family of four G-protein coupled receptors and the P2, a family of at least 12 receptors responsive to purine (ATP, ADP) and pyrimidine (UTP) nucleotides through which adenosine and ATP can function as extracellular messengers. The present two-part volume represents an integrated compendium of invited chapters by leading researchers in the area focusing on advances in the understanding of purinergic and pyrimidinergic signaling systems, their role(s) in tissue function and pathophysiology and advances in developing potential new medications based on the modulation of P1 and P2 receptor signaling processes. The volumes will thus provide the reader with a topical, comprehensive and integrated overview of this important area.

In recent years there have been various discoveries connecting inflammation and lung cancer and clearly there is growing interest in this area of cancer research. The link between unresolved inflammation and cancer has been well established with estimates that 15% of cancer deaths are inflammation-related. Evidence for this link includes the following: a) some inflammatory diseases are associated with increased risk of cancer development; b) inflammatory mediators are present surrounding and within most tumors; c) overexpression of inflammatory cytokines increases cancer development and progression in murine studies; d) inhibition of inflammatory mediators decreases cancer development and progression; and e) the use of non-steroidal anti-inflammatory drugs (NSAIDs) has been found to decrease cancer incidence and delay progression. The volume will present aspects of the inflammatory tumor microenvironment (TME), its many roles in tumor progression and metastasis, including creation of a hypoxic environment, increased angiogenesis and invasion, changes in expression of micro-RNAs (miRNAs) and an increase in a stem cell phenotype. The book will also cover the mechanisms of inflammatory mediators. Chronic overexpression of inflammatory mediators in the TME, as seen in smokers and patients with non-small cell lung cancer (NSCLC), can also lead to increased tumor initiation, progression, invasion and metastasis. The volume will provide a comprehensive perspective of the latest findings and summaries of progress made regarding inflammation and its connection to lung cancer.

Systemic Lupus Erythematosus: Methods and Protocols describe a number of genetic, biochemical and immunological techniques. These techniques provide an advancing understanding of the pathology, breakdown of the immune system and therapeutic challenges of SLE in both humans and animal models. 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, Systemic Lupus Erythematosus: Methods and Protocols appeal to biomedical and clinical scientists in a number of pathology disciplines at the doctoral and post-doctoral level.

Virus Variability and Impact on Epidemiology and Control of Diseases E. Kurstak and A. Hossain I. INTRODUCTION An important number of virus infections and their epidemic developments demonstrate that ineffec tiveness of prevention measures is often due to the mutation rate and variability of viruses (Kurstak et al., 1984, 1987). The new human immunodeficiency retroviruses and old influenza viruses are only one among several examples of virus variation that prevent, or make very difficult. the production of reliable vaccines. It could be stated that the most important factor limiting the effectiveness of vaccines against virus infections is apparently virus variation. Not much is, how ever, known about the factors influencing and responsible for the dramatically diverse patterns of virus variability. II. MUTATION RATE AND VARIABILITY OF HUMAN AND ANIMAL VIRUSES Mutation is undoubtedly the primary source of variation, and several reports in the literature suggest that extreme variability of some viruses may be a consequence of an unusually high mutation rate (Holland et al., 1982; Domingo et al., 1985; Smith and Inglis, 1987). The mutation rate of a virus is defined as the probability that during a single replication of the virus genome a particular nucleotide position is altered through substitution, deletion, insertion. or recombination. Different techniques have been utilized to measure virus mutation rates, and these have been noted in the extent of application to different viruses."

The B7-CD28 family molecules are probably the most intensively studied receptor-ligand systems in the field of immunology. This is evident from the explosive accumulation of literature, particularly in the last ten years. Recent years have witnessed rapid discoveries and characterization of new receptors and ligands in the family. These new pathways, although still in their infancy, have already brought much excitement to the field. However, until now, there has been no single volume to cover this entire area. This book was created to bring together state-of-the-art information and critical thinking from the leading investigators. This book covers significant territory of this rapidly moving field from structural biology and biochemical signalling to immunological functions and their potential applications in the treatment of human diseases. This is an excellent handbook and reference for immunologists, health professionals as well as medical students and graduate students in life science field.

Multipotent mesenchymal stem cells (MSCs) are a heterogeneous population of cells which reside in a variety of tissues. They differentiate into several mesodermal lineages, secrete a multitude of trophic factors and contribute to tissue homeostasis. MSCs are able to exert immunosuppressive activities by interfering with inflammatory cytokine production and with T- and B-cell proliferation. These immunomodulating properties make MSCs promising candidates for the treatment of chronic inflammatory and autoimmune disorders. There are, however, certain caveats involved including inappropriate migration of cells in the body, immune rejection, tumor formation, or graft versus host disease (GvHD). This book investigates the current state of the MSC-dependent therapy of chronic inflammatory disorders and autoimmune diseases. Among the covered topics are GvHD, chronic kidney, liver and lung disease, ischemic heart and inflammatory bowel disease, diabetes, osteoarthritis, various rheumatic and neurological disorders and, lastly, tumors and solid organ transplantations. This book also questions the immunoprivileged status of MSCs, discusses the therapeutic role of MSCs in experimental animal disease models and their translation to the corresponding human disorders, envisions a role for MSCs in tumor interventions and, lastly, describes a systems biology approach for stem cells and inflammation.

In this issue, guest editors bring their considerable expertise to this important topic. Provides in-depth reviews on the latest updates in the field, providing actionable insights for clinical practice. Presents the latest information on this timely, focused topic under the leadership of experienced editors in the field. Authors synthesize

For over 10 years, TMV -based vectors have been used as plant expression tools to examine gene regulation and function, protein processing, pathogen elicitors, to manipulate biosynthetic pathways, and to produce high levels of enzymes, proteins, or peptides of interest in different locations in a plant cell. TMV vectors often exhibit genetic stability of foreign RNA sequences through multiple passages in plant hosts. Foreign coding sequences can be expressed in plants where the stability, intracellular fate and enzymatic or biological activities of the recombinant proteins can be rapidly evaluated and optimized. These properties make viral vectors attracti ve expression vehicles for testing and production of a wide variety of recombinant peptides and proteins, for structural analyses of post-translational modifications and for assessing gene function and metabolic control. Finally, the utility of both CP fusion and dual subgenomic vectors has extended beyond the laboratory and greenhouse to field-scale production and purification of recombinant products for commercial use (Grill, 1992; Grill, 1993; Turpen et at. , 1997). REFERENCES Copeman RJ, Hartman IR and Watterson IC. 1969. Tobacco mosaic virus in inoculated and systemically infected tobacco leaves. Phytopathology 59: 1012-1013. Dawson WO, Beck DL, Knorr DA and Grantham GL. 1986. cDNA cloning of the complete genome of tobacco mosaic virus and production of infectious transcripts. Proc. Natl. Acad. Sci. (USA) 83: 1832-1836. Dawson WO and Lehto KM. 1990. Regulation of tobamovirus gene expression. Ad. Virus Res. 38:307-342. Dawson WOo 1992. Tobamovirus-Plant Interactions. Virology 186:359-367.

The fast development in the field of nanotechnology has led to a high variety of nanoparticles. Nanoparticles find importance in every sphere of human lives and more so in the recent years have tremendous applications in the sector of biomedical clinical medicine as diagnostic, prognostic and imaging tools. Their risk to human and animal life as well as to the environment is still unclear. Therefore, the study of the impact of nanoparticles on human and animal life is important. Volume I highlights the impact of nanoparticles on the human immune system. While discussing the basic biology of the immune system, this book highlights the downstream effect of nanoparticles on the human immune system. Research studies on the development of better and more effective nanoparticles with more precise and accurate effects and with toxic minimal side effects are discussed in the book. Both volumes are also included in a set ISBN 978-3-11-065666-4.

This book explores the major cytokines, such as IL-1 and IFN- , with respect to the regulation of their gene expression and protein production in specific immune cell types. It discusses both healthy physiological settings and in pathological situations in which the expression of some cytokines could be dysregulated, resulting in either immunodeficiency or exacerbated inflammatory sequelae in animal models as well as in human patients. Cytokines are important regulators of immune responses that require the highly coordinated participation and communication of multiple cell types. The expression of cytokines by various producer cell types is therefore carefully regulated in response to environmental cues at multiple levels: transcription, translation and posttranslational modification. Presenting cutting-edge advances in our understanding of the regulation of cytokine expression, this book is a valuable resource for anyone involved or interested in immune regulation.

The study of immunology encompasses a vast and ever-growing body of information that in some way or other incorporates most areas of medical biological research. As the body of information in the medical sciences continues to increase its rate of expansion, one of the greatest challenges to investigators will be to integrate this information in a manner that is intellectually fruitful and productive. Considering the intended scope of this text, we could not pretend to have gone too far toward achieving such an integration--and considering the pace of change, in its very best form a measured approximation of such lofty goals might be the most we could hope for. Nevertheless, in these pages we have sought to produce a collection of information that is at once concise and up-to-date regarding areas where important developments are impacting on the way we understand the vertebrate immune system. In addition, although the information is geared toward advanced study, we have discussed some basic elements and concepts that we hope make the text a useful resource for both the immunologist and the nonspecialist. The intention is to provide the researcher, clinician, or advanced undergraduate student with a brief ov- view of specific components of the immune system, and to provide a place from which to begin further detailed study if necessary. To this end, we made every effort to supply extensive referencing--although limitations in space prevented exhaustive or complete referencing in some cases.

Course covers topics in infectious diseases in children and is intended for Pediatric Infectious disease trainees, trainers, and all those who manage children with infections.

The culmination of 30 years of research and experience in T-cell-based cancer, this book highlights and evaluates new treatments that harness the power of the T cell to attack and kill all cancer cells in our bodies. It describes how the T cell immune system can be manipulated and redirected to kill resistant cancer cells by understanding and influencing the interaction of many different immune cells in the body. Citing current experimental trials, it examines the role and pathology of T-cells and suggests additional experimental approaches to the problem.

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."

The ability to remember an antigenic encounter for several decades, even for a life time, is one of the fundamental properties of the immune system. This phenomenon known as "immunological memory," is the foundation upon which the concept if vaccination rests. Therefore, understanding the mechanisms by which immunological memory is regulated is of paramount importance. Recent advances in immunology, particularly in the field of innate immunity, suggest that the innate immune system plays fundamental roles in influencing immunological memory. Indeed, emerging evidence suggests that events that occur early, within hours if not minutes of pathogen or vaccine entry profoundly shape the quantity, quality and duration of immunological memory. The present volume assembles a collection of essays from leading experts that span the entire spectrum research from understanding the molecular mechanisms of innate immune recognition, to dendritic cell function, to the generation and maintenance of antigen-specific B and T-cell responses.

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.

"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."

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."

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".

A New History of Vaccines for Infectious Diseases: Immunization - Chance and Necessity covers the developments of vaccines and how they have obliterated many fatal diseases and infections over time. The book treads a neutral path but does not avoid discussion. As uncertainty in the outcome of vaccination can only be determined by experiment, the path to vaccine development has been scientifically complex because the immune system and the manner in which humans respond to infection is variable and complex. Finally, the book describes the risks and benefits of vaccines in a visibly objective manner.

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.

Comparative Mammalian Immunology: The Evolution and Diversity of the Immune Systems of Mammals provides a review on the current knowledge of mammalian immune systems from a comparative viewpoint. This reference encompasses recent work on the immune systems of marine mammals, bats and marsupials in addition to other lesser-known species, with the immune systems of humans and laboratory mice as components of chapters on primates and rodents respectively. The book also makes use of the most recent studies on the genomic sequences of the mammals to identify both common and unique features of each mammal's immune system. The book elucidates the complex, but coordinated and controlled series of interactions involving cells and molecules that has evolved to protect the host against disease. Mammals consist of a highly diverse group of animals in which the immune system has been subjected to a variety of selective pressures. This is reflected in differences in the organization and function of their immune systems, and is especially seen in those gene families characterized by complexity and polymorphism.