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

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

Dendritic Cells in the Induction of Immunity.- Escape Mechanisms of Viruses from Immune Responses and Their Relevance to Vaccine Design.- Enhanced Immunogenicity of Recombinant and Synthetic Peptide Vaccines.- Immunomodulation by Adjuvants.- Use of Syntex Adjuvant Formulation to Enhance Immune Responses to Viral Antigens.- Influenza Vaccines and the Wyeth-Ayerst Experience with Syntex Adjuvant.- Nonionic Block Polymer Surfactants as Adjuvants in Vaccines.- Effects of Added Cytokines on Immune Responses and Memory.- The Assessment and Use of Adjuvants.- Efficient Anti-Idiotypic Immunization with Homologous, Virus Neutralizing Monoclonal Antibodies Conjugated with KLH and Combined with Quil A.- Protein Conformation Affects the Efficacy of Pertussis Vaccines.- Vaccination Against Epstein-Barr Virus.- Adenovirus Vectored Vaccines.- Vaccines Against Bacterial Infections of Children.- Current Progress and Future Trends in Birth Control Vaccines.- Contributors.

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

In situ hybridization has developed as a means of localizing specific DNA and RNA sequences within tissues. The great strength of this approach is the ability to relate the distribution of specific nucleic acids with cell structures and the protein products of the target gene by means of immunohistochemistry. Complementary DNA, RNA or oligonucleotide probes, suitably labelled, are hybridized to specific DNA or RNA targets within tissues. The spatial information thus obtained has contributed greatly to our understanding of such diverse areas of research as gene mapping, viral infection, cytogenetics, protein synthesis, prenatal diagnosis and tissue grafting. This book is not intended as another recipe book, although it does describe theoretical and practical aspects of the technology. Rather, the authors critically describe the contribution made by in situ hybridization to specific areas of medical research.

In spite of the protection of the CNS there are situations where immune responses occur due to different disease processes. While antigen-specific cells of the adaptive immune response are not normally functional in the CNS tissue, CNS resident cells respond to infection or insult. One mechanisms is through the induction of apoptosis in virus infected neurons, which may be protective or pathogenic depending on the extent of cell death.

Recent research indicates that the immune system and inflammatory reactions are governed and regulated by powerful neuronal mediators derived from the central and peripheral nervous system. The NPY family of peptides is a diverse group of neuropeptides that acts via multiple receptors, Y1-Y5, which are widespread not only in neurons but also in a variety of non-neural and immune cells. These peptides have been known as important regulators of many essential systems, such as blood pressure and cardiac function, food consumption and energy homeostasis. However, in recent years, they have also become recognized for their role as potent modulators of cell growth and immune functions with broad implications in chronic inflammatory diseases, cancer and angiogenesis.
In this book, experts in the field analyze recent evidence supporting the role of NPY family of peptides in regulation of the immune/inflammatory system with special reference to its medical and therapeutic implications.

Antimicrobial peptides have been the subject of intense research in the past decades, and are now considered as an essential part of the defense system in bacteria, plants, animals and humans. This book provides an update on these effector molecules of the innate immune system both for researchers who are already actively involved in the area, and for those with a general interest in the topic. The book starts with an overview of the evolution of cysteine- containing antimicrobial peptides (including defensins), and the role of these peptides in host defense in plants and micro- organisms. The realization that antimicrobial peptides also display functions distinct from their direct antimicrobial action is the focus of the next chapters, and puts these peptides center stage in immunity and wound repair. Further chapters discuss the role of antimicrobial peptides in disease, by providing an overview of mechanisms in bacterial resistance to antimicrobial peptides and a discussion of their role in inflammatory bowel disease, cystic fibrosis lung disease and chronic obstructive pulmonary disease. Finally, the book shows how knowledge of the function of antimicrobial peptides and their regulation can be used to design new therapies for inflammatory and infectious disorders. This is a very important area of research because of the increase in resistance of micro-organisms to conventional antibiotics. Therefore the use of synthetic or recombinant peptides, or agents that stimulate the endogenous production of antimicrobial peptides, provides an attractive alternative for conventional antibiotics.

The book summarizes our progress in understanding the receptor and intracellular signaling mechanisms utilized by a family of proteins called the semaphorins. Originally these protein were identified as axon guidance cues important for the formation of nerve tracts but now it is realized that semaphorins subserve several distinct functions in a multitude of organ systems. The purpose of this book is to summarize our knowledge and make it available as a useful and comprehensive tool for the scientific community. This book will both be interesting for people working in the field as well as colleagues that work in other fields of science and would like to learn more about semaphorins and associated signaling mechanisms. All the latest techniques and results are summarized in this book which covers the entire semaphorin field from neurosciences to cardiovascular research and beyond. The strength of this book is that it gives a very comprehensive overview of all our knowledge of semaphorin biology and signaling and allows one to compare semaphorin functions between different biological systems.

This volume examines in detail the role of chronic inflammatory processes in the development of several types of cancer. Leading experts describe the latest results of molecular and cellular research on infection, cancer-related inflammation and tumorigenesis. Further, the clinical significance of these findings in preventing cancer progression and approaches to treating the diseases are discussed. Individual chapters cover cancer of the lung, colon, breast, brain, head and neck, pancreas, prostate, bladder, kidney, liver, cervix and skin as well as gastric cancer, sarcoma, lymphoma, leukemia and multiple myeloma.

Cellular Mechanisms Involved in the Modulation of the Immune System by Drugs of Abuse; S.L. Chang, et al. Immunomodulation of Macrophage Functions by Opioids; R. Gomez-Flores, R.J. Weber. Morphine Accelerates the Progression of Sepsis in an Experimental Sepsis Model; S. Roy, et al. Morphine Depresses Macrophage Numbers and Function in Mouse Spleens; T.K. Eisenstein, et al. Morphine Depresses Macrophage Numbers and Function in Mouse Spleens; T.K. Eisenstein, et al. Centrally-Mediated Opioid-Induced Immunosupression: Elucidation of Sympathetic Nervous System Involvement; W.J. Brinkman, et al. The Expression of Interleukin-1beta Converting Enzyme (ICE) in Rat is Decreased Following Chronic Exposure to Morphine; Gao-de Wu, et al. Opioid Receptor Gene Expression in the Porcine Immune System; M.S. Pampusch, et al. The Effects of Interaction Between Morphine and Interleukin-1 on the Immune Response; S.L. Chang, et al. Morphine Alters the Immune Response to Influenza Virus Infection in Lewis Rats; M.E. Coussons-Read, et al. Orphan Opioid Receptor Oligonucleotide Inhibit HIV-1 Expression in Human Brain Cells; C.C. Chao, et al. Opiate Effects on in Vitro Human Retroviral Infection; S.B.Nyland, et al. FIV: A Lentivirus Model for Opiate Effects on Disease; J.-N. Billaud, T.R. Phillips. 21 Additional Articles. Index.

Mammalian Toll-like receptors (TLRs) were first identified in 1997 based on their homology with Drosophila Toll, which mediates innate immunity in the fly. In recent years, the number of studies describing TLR expression and function in the nervous system has been increasing steadily and expanding beyond their traditional roles in infectious diseases to neurodegenerative disorders and injury. Interest in the field serves as the impetus for this volume in the Current Topics in Microbiology and Immunology series entitled "Toll-like receptors: Roles in Infection and Neuropathology." The first five chapters highlight more traditional roles for TLRs in infectious diseases of the CNS. The second half of the volume discusses recently emerging roles for TLRs in non-infectious neurodegenerative diseases and the challenges faced in these models with identifying endogenous ligands. Several conceptual theories are introduced in various chapters that deal with the dual nature of TLR engagement and whether these signals favor neuroprotective versus neurodegenerative outcomes. This volume should be informative for both experts as well as newcomers to the field of TLRs in the nervous system based on its coverage of basic TLR biology as well as specialization to discuss specific diseases of the nervous system where TLR function has been implicated. A must read for researchers interested in the dual role of these receptors in neuroinfection and neurodegeneration.

This volume details our current understanding of the architecture and signaling capabilities of the B cell antigen receptor (BCR) in health and disease. The first chapters review new insights into the assembly of BCR components and their organization on the cell surface. Subsequent contributions focus on the molecular interactions that connect the BCR with major intracellular signaling pathways such as Ca2+ mobilization, membrane phospholipid metabolism, nuclear translocation of NF-kB or the activation of Bruton's Tyrosine Kinase and MAP kinases. These elements orchestrate cytoplasmic and nuclear responses as well as cytoskeleton dynamics for antigen internalization. Furthermore, a key mechanism of how B cells remember their cognate antigen is discussed in detail. Altogether, the discoveries presented provide a better understanding of B cell biology and help to explain some B cell-mediated pathogenicities, like autoimmune phenomena or the formation of B cell tumors, while also paving the way for eventually combating these diseases.

It has been clear for a long time that after transplantation of a lymphoid organ, hematopoietic stem cells can regenerate the compartments of the organ, provided that the rest of its architecture - the strome, the epithelia and the vessels - is intact. Ahead lies the even greater challenge to assemble also these other architectural elements of a lymphoid organ by transplanting stem cells. The workshop on lymphoid organogenesis was convened to review current knowledge of and experimental skills involved in this grand project to build a lymphoid organ from its individual cellular components.

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.

Complement has long been regarded as a pivotal effector arm of the innate immune response, eliciting important immunoregulatory functions in the context of inflammation and also serving as a vital link between the innate and adaptive immune response. In the post-genomic era, our knowledge of the innate immune system is enriched by findings that point to novel functions that do not strictly correlate with immunological defense and surveillance, immune modulation or Inflammation. Several studies indicate that complement proteins exert functions that are either more complex than previously thought, or go well beyond the innate immune character of the system. The advent of high-throughput platforms for genome and proteome-wide profiling, together with the enormous amount of raw genetic information that has accumulated in the databases, have stirred new expectations in biomedical research. They have led complementologists to revisit established biological systems, such as the complement system, from a global and integrative perspective. Complement research is now faced with the challenge of trying to integrate isolated biochemical pathways into complex gene and protein regulatory circuits.

In this respect, scientists from around the world convened at the Fourth Aegean Conferences Workshop on Complement Associated Diseases, Animal Models, and Therapeutics (June 10-15, 2007), to discuss recent advances in this fast evolving field. This volume represents a collection of topics on the "novel" functions of complement, patho-physiology, protein structures, design of complement inhibitors, and complement assays discussed during the conference.

th This volume contains selected lectures presented at the 12 International Conference on Advances in Prostaglandin, Leukotriene and Other Bioactive Lipid Research: Basic Science and Clinical Applications which was held in Istanbul, Turkey, on August 25-29, 2002. This meeting brought together basic and clinical scientists for the purpose of discussing advances in bioactive lipid research with.special attention to cancer, cardiovascular diseases, gastrointestinal diseases and respiratory diseases. Topics covered included: the role of leukotrienes and lipoxins in of inflammation, the cytochrome P450 pathway, the genetics and genomics bioactive lipids, lipid peroxidation, apoptosis, angiogenesis, isoprostanes, receptors and inhibitors, cyclooxygenase and lipoxygenase pathways and inhibitors, prostaglandin synthases and receptor signaling, phospholipases and inhibitors. Sessions included plenary lectures with expertise in particular areas, oral presentation on selected topics and general poster sessions. J.M. Drazen (Boston, USA) discussed anti-leukotriene treatment in asthma patients while C. Brink (paris, France) presented the recent advances in leukotriene receptors. The recent advances in cytochrome p450 pathway described in the session organized by J.C. McGiff (Valhalla, NY, USA). T. Shimizu (Tokyo, Japan) and M. Balazy (Valhalla, NY, USA) gave an update on phospholipases and arachidonic acid peroxydation. The editors are greatful to the Organizing, Programme and Advisory Committees for their valuable contributions. We greatfully acknowledge the generous financial support provided by PharmaciaIPfizer, Fako Pharmaceuticals Inc. and Novartis Pharmaceuticals Inc. ofthe contributors to this volume, in particular We are also greatful to all to those who delivered their manuscripts by or before the requested deadline.

This volume focuses on the relationship between the nervous and the immune system with regard to the effects of drugs of abuse and infections, including infection caused by the immunodeficiency virus which causes AIDS, the number one health problem worldwide. Chapters focus on the brain-immune axis, detailing the effects of drugs of abuse. It is well known that recreational drugs of abuse such as morphine, cocaine, and marijuana, as well as other drugs, including the legal drugs alcohol and nicotine, are used by large numbers of individuals. Serious concerns have been raised about the consequences of using such drugs, especially in relation to their effects on normal physiological responses, including immune mechanisms. It is now widely recognized not only that many drugs of abuse have serious consequences on normal parameters of neurologic and neuroendocrine systems in general but also that effects on those systems, in turn, may affect indirectly immunity and also directly affect immune systems. Much data has now been accumulated showing that drugs of abuse markedly alter the immune response in human populations as well as in experimental animals, both in vivo and in vitro. Furthermore, studies on microbial infections have shown that many drugs of abuse are associated with increased susceptibility to infectious diseases, especially opportunistic intracellular microorganisms, including viruses such as HIV which causes AIDS. The mechanisms whereby drugs of abuse increase the likelihood of infections by opportunistic microorganisms in humans as well as in experimental animals are delineated. This volume will further the understanding of the impact of drugs of abuse on the brain-immuneaxis and its relationship to immunomodulation and infection, especially that caused by the AIDS virus.

The intestine is the front line of the confrontation between pathogens and the immune system. However, it is also important to emphasize that we have a symbiotic relationship with innumerable bacteria in the intestine. In the gastrointestinal tract of mammals the lower intestine harbors around 1,000 12 species of anaerobic and aerobic bacteria, in densities up to 10 /mlinthe distal small intestine, the cecum, and the colon. A single layer of epithelial cells of the intestine protects the internal organs of the mammalian host from these bacteria. Below these epithelial cells the gut-associated lymphoid tissues (GALT), organized in Peyer's patches, cryptopatches, and isolated l- phoid follicles, as well as isolated, dispersed single cells in the epithelial layer (intraepithelial lymphocytes) and lamina propria, are composed of T l- phocytes, B lymphocytes, Ig-secreting plasma cells, and antigen-presenting cells such as dendritic cells. The importance of the gut barrier is striking, if we consider that in humans the epithelial surface, behind which the immune system faces and senses the endogenous bacteria, is estimated to be as large as a basketball court. Perhaps not surprising then, the gut contains appr- imately half of all lymphocytes of our immune system. Colonization of the intestine with the ?ora of commensal bacteria induces the development of the GALT, which in turn responds by the development of IgA-secreting plasma cells. Dimeric and multimeric IgAs can traverse the epithelial layer and are released in the gut lumen, where they bind bacteria.

The HLA molecules are important regulators of the immune response through mediating antigen presentation and interaction between key immune mediating cells. They are also the major histocompatibility barriers to transplantation, which is the clinical paradigm of the self versus non self concept. It is now recognized that this diverse range of gene systems involved in the control of the immune response have been shown to be important in many aspects of clinical practice. As a result many new molecular and cellular methods have been developed for identifying these genes and their polymorphisms, and immunogenetic laboratories specializing in these methods have developed to support transplantation and other clinical programs. "Immunogenetics: Methods and Applications in Clinical Practice "focuses on methods for human clinical practice. The emphasis rests on those assays which are of established or potential clinical utility and are likely to be included in the repertoire of tests provided by a routine diagnostic and service laboratory. This volume also contains several review chapters of the MHC complex, the KIR complex, the human immunoglobulin allotypes, as well as reviews of the methods for the detection of alloreactive NK cells and the detection of HLA antibodies by solid phase assays. 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, "Immunogenetics: Methods and Applications in Clinical Practice "seeks to serve both the immunogenetics community and the wider scientific community with a collection of detailed information and helpful tips attained by many years of experience in the field.

Adaptive immune responses serve as a key defense mechanism for the control of infections in vertebrates. Immune responses must be of sufficient strength to contain invading pathogens, antigen specific responses require regulatory mechanisms to ensure termination or downmodulation to avoid excessive damage to the host tissue. For both branches of the adaptive immune system, regulatory molecules i.e. coreceptors and ligands have been identified that control the signaling cascades initiated by engagement of the T cell and B cell antigen receptors. This book describes biological functions as well as molecular mechanisms of these molecules. Fc Receptor-Like molecules (FCRL) that have garnered increasing interest due to their differential patterns of lymphocyte expression and potential involvement in the pathogenesis of autoimmune disorders, immunodeficiency and lymphoid malignancies in humans. Programmed cell death-1 (PD-1) delivers negative signals upon interaction with its two ligands, PD-L1 or PD-L2. The biological significance of PD-1 and its ligand suggest the therapeutic potential of manipulation of PD-1 pathway against various human diseases. TIM-3 acts as a negative regulator of Th1/Tc1 cell function by triggering cell death upon interaction with its ligand, galectin-9. This negative regulatory function of TIM-3 has now been expanded to include its involvement in establishing and/or maintaining a state of T cell dysfunction or exhaustion' observed in chronic viral diseases. The Ly49 receptors, which are expressed in a stochastic manner on subsets of murine Natural Killer (NK) cells, T cells, and other cells, are encoded by the Klra gene family and include receptors with either inhibitory or activating function. Most of the inhibitory Ly49 receptors recognize polymorphic epitopes on major histocompatibility complex (MHC) class I proteins as ligands. Fc-receptors for IgG (Fc?Rs) are widely expressed on innate immune effector cells in

Our understanding of inflammation has increased rapidly in recent years, due in large part to the impact of molecular biology and gene identification and cloning. This book brings together ideas from a number of different biochemical disciplines which are frequently not integrated. The first chapter gives a visual overview of the subject; the remaining chapters are organized into three themes: the affector molecules, the regulatory components and the processes of inflammation itself. This book is essential reading for the busy physician or pathologist who wants to be up-to-date with the latest developments in immunology as they affect the diagnosis and treatment of many conditions.

This authored book presents basic immunological tenets and mechanisms at the cellular and molecular level while employing the toxicology focus on hazard identification, appropriate assays, dose response, and risk assesment by mathematical models and safety factors. It will be a useful reference to toxicologists because it will incorporate new guidelines that the EPA is bringing out later this year for all chemicals regulated under the Federal Insecticide, Fungicide, and Rodenticide Act and the Toxic Substances Control Act. Regulatory sections in each chapter focus on data from both the US Food and Drug Administration, as well as data applicable to western European Nations.

The justification for yearbooks is greater than ever as we approach the third millennium, overwhelmed with information. This first edition of the Cytokine Yearbook summarizes the latest advances in the revolutionary field of cytokine research. The work is not a comprehensive reference work, but covers a selection of current themes. The intention is to keep paying attention to current topics in the Yearbooks to come. The editors invited a number of distinguished colleagues, who are international experts in their specific fields, resulting in a high scientific level of the contributions. This Yearbook is required reading for every scientist and physician working in the field of cytokines.

"De la vaporisation et de la centralisation du Moi. Tout est la. " Charles Baudelaire (journal entry) This anthology is my visit to Oz. On sabbatical in 1988, I chose to reeducate myself in general biology, first broadening my erudition as an immunologist, and then extending that horizon into evolutionary biology and embryology. I was particularly attracted to reflections on the nature of the self as an organ ismic concept. I went in search of reorientation as a confused physician scientist, and came back with this book. Baum's Wizard of Oz presented opportunities for growth, and herein lies the purpose of this volume: in providing updated statements concerning the nature of the organism from both scientific and metaphysical perspectives, we might ponder the philo sophical basis of our research in the hope of gaining insight into our endeavor, not to mention the possibility of its enrichment; it is this contem plative view of our research which offers a unique dimension to this anthology. To that end, the project follows my idiosyncratic prejudices. The anthology derives in large measure from the symposium, "Organism and the Origin of Self' held at Boston University, April 3-4, 1990, under the auspices of the Boston University Center for the Philosophy and History of Science, with generous support of Robert Cohen and Jon Westling, and the organizational skills of Deborah Wilkes. The Symposium presented three ver sions of the Self from the vantages of embryology, evolution and medicine."