Immunology is a nodal subject that links many areas of biology. It permeates the biosciences, and also plays crucial roles in diagnosis and therapy in areas of clinical medicine ranging from the control of infectious and autoimmune diseases to tumour therapy. Monoclonal antibodies and small molecule modulators of immunity are major factors in the pharmaceutical industry and now constitute a multi billion dollar business. Students in these diverse areas are frequently daunted by the complexity of immunology and the astonishing array of unusual mechanisms that go to make it up. Starting from Dobzhansky's famous slogan, "Nothing in biology makes sense except in the light of evolution", this book will serve to illuminate how evolutionary forces shaped immunity and thus provide an explanation for how many of its counter intuitive oddities arose. By doing so it will provide a conceptual framework on which students may organise the rapidly growing flood of immunological knowledge.

Novel molecular motifs named Immunoreceptor Tyrosine-based Inhibition Motifs (ITIMs) have recently been recognized in the intracytoplasmic domains of a still-increasing number of receptors which control cell activation and proliferation. Research on ITIM-bearing molecules has developed exponentially during the last three years, generating new concepts with important consequences in basic research and with exciting potential clinical applications. The present volume contains 15 reviews written by authors who all made significant contributions to the identification of ITIM-bearing molecules and the study of their biological properties. It constitutes the first synthesis ever published that is specifically devoted to this emerging topic.

This work provides rapid access to focused information on topics of Immunotoxicology not only for scientists and those dealing with laboratory aspects but also for lecturers and advanced students. Over 200 contributing authors - including many of the world's top specialists - have contributed full essays on all relevant topics, supplemented by keyword definitions of related terms. Full essays are structured uniformly to provide reader-friendly information on all aspects of Immunotoxicology, including methods of testing and analysis, characteristics of substances, the regulatory environment and the relevance of these to humans.

This book provides a detailed account of the most recent developments, challenges and solutions to seamlessly advance and launch a lyophilized biologics or vaccine product, based on diverse modalities, ranging from antibodies (e.g., monoclonal, fused), complex biologics (e.g., antibody drug conjugate, PEGylated proteins), and vaccines (e.g., recombinant-protein based). The authors adeptly guide the reader through all crucial aspects, from biophysical and chemical stability considerations of proteins, analytical methods, advances in controlled ice nucleation and quality-by-design approaches, alternate drying technology, to latest regulatory, packaging and technology transfer considerations to develop a stable, safe and effective therapeutic protein, vaccine and biotechnology products. Lyophilized Biologics and Vaccines: Modality-Based Approaches is composed of four sections with a total of 17 chapters. It serves as a reference to all critical assessments and steps from early pre-formulation stages to product launch: Provides recent understanding of heterogeneity of protein environment and selection of appropriate buffer for stabilization of lyophilized formulations Details the latest developments in instrumental analysis and controlled ice nucleation technology Explains in-depth lyophilized (or dehydrated) formulation strategies considering diverse modalities of biologics and vaccines, including plasmid DNA and lipid-based therapeutics Details an exhaustive update on quality-by-design and process analytical technology approaches, illustrated superbly by case studies and FDA perspective Provides the latest detailed account of alternate drying technologies including spray drying, bulk freeze-drying and crystallization, supported exceptionally by case studies Provides a step-by-step guide through critical considerations during process scale-up, technology transfer, packaging and drug delivery device selection, for a successful lyophilization process validation, regulatory submission and product launch Chapters are written by one or more world-renowned leading authorities from academia, industry or regulatory agencies, whose expertise cover lyophilization of the diverse modalities of biopharmaceuticals. Their contributions are based on the exhaustive review of literature coupled with excellent hands-on experiences in laboratory or GMP setup, making this an exceptional guide to all stages of lyophilized or dehydrated product development.

This volume presents a collection of reviews derived from work presented at the Aegean Conference: "5th Crossroads Between Innate and Adaptive Immunity". This meeting was the fifth in a series, and assembled a team of scientists working on mechanisms by which the innate immune system of the host senses pathogens, the cellular and signaling networks that orchestrate the innate response and antigen presentation and adaptive immunity. The importance of the crosstalk between innate immunity and the adaptive immune response has only recently started to be appreciated. Although it is well recognized that dendritic cells, NK cells, NK-T cells and T cells are all critical for the host response to pathogens, the respective fields that study the biology of these immune cells tend to exist in parallel worlds with minimum exchange of information and ideas. This fragmentation hinders the integration of these fields towards a unified theory of host response. The Aegean Conference "Crossroads between Innate and Adaptive Immunity" brought together leading international scientists and experts to address critical areas of Innate and Adaptive Immunity, a necessary step in the development of more efficient scientific exchange and crosspollination between these fields. This conference attracted scientists from all over the world to discuss their latest findings on the various aspects of Innate and Adaptive Immunity, and maximized scientific interchange through lecture presentations, poster sessions and informal discussions.

A great deal of effort is being invested in understanding the molecular mechanisms through which plants interact with pathogenic microbes. In Plant Immunity: Methods and Protocols, expert researchers in the field describe emerging technologies that can be applied to the most significant outstanding questions faced by scientists studying immunity in plants. The technologies in this detailed volume include methods for examining protein localization, protein complex purification, protein-protein interactions, transient and inducible gene expression, chromatin immunoprecipitation, microaspiration, laser microdissection, purification of fungal haustoria, and genetic manipulation of bacterial and oomycete pathogens. These techniques are applicable to a wide range of topics, including molecular functionality of NB-LRR proteins and other immune signaling components, and functional characterization of effector proteins and other pathogen components that sabotage host immunity. Written in the highly successful Methods in Molecular Biology (TM) 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.

The volume focuses on the genomics, proteomics, metabolomics, and bioinformatics of a single cell, especially lymphocytes and on understanding the molecular mechanisms of systems immunology. Based on the author's personal experience, it provides revealing insights into the potential applications, significance, workflow, comparison, future perspectives and challenges of single-cell sequencing for identifying and developing disease-specific biomarkers in order to understand the biological function, activation and dysfunction of single cells and lymphocytes and to explore their functional roles and responses to therapies. It also provides detailed information on individual subgroups of lymphocytes, including cell characters, function, surface markers, receptor function, intracellular signals and pathways, production of inflammatory mediators, nuclear receptors and factors, omics, sequencing, disease-specific biomarkers, bioinformatics, networks and dynamic networks, their role in disease and future prospects. Dr. Xiangdong Wang is a Professor of Medicine, Director of Shanghai Institute of Clinical Bioinformatics, Director of Fudan University Center for Clinical Bioinformatics, Director of the Biomedical Research Center of Zhongshan Hospital, Deputy Director of Shanghai Respiratory Research Institute, Shanghai, China.

"Immuno Systems Biology" aims to study the immune system in the more integrated manner on how cells and molecules participate at different system levels to the immune function. Through this bookKumar Selvarajoointroduces to physicists, chemists, computer scientists, biologists and immunologists the idea of an integrated approach to the understanding of mammalian immune system. Geared towards a researcher with limited immunological and computational analytical experience, the book provides a broad overview to the subject and some instruction in basic computational, theoretical and experimental approaches. The book links complex immunological processes with computational analysis and emphasizes the importance of immunology to themammalian system. "

During the past five years major progress has been made in understanding the basic mechanisms of lymphocyte homeostasis and in the developmental relationship between different memory T subsets and their traffic patterns and functional significance. This volume highlights the current concepts of lymphocyte development, factors regulating lymphocyte trafficking and development, and specialized characteristics and functional properties of naive and memory subsets. This volume is divided into three sections. Section I deals with factors that regulate the development and maturation of T cells and B cells and lymphocyte traffic. The significance of C-kit, Bcl-6, IL-7, and Vav in the development of T and B lymphocytes is discussed. A role of lymphotoxins and VAP-I in trafficking of leucocytes is reviewed. Finally, the trafficking and homing characteristics of T cell and B cell subsets, and the regulation of these processes during the immune response, is presented. Section II discusses various aspects of naive and memory T cell biology, including clonal expansion, reprogramming of genes including those encoding cytokines and cytotoxic granules, changes in the expression of cell surface proteins involved in cell-cell adhesion, homing of naive and memory T cells, the role of MHC and cytokines in the maintenance of naive and memory T cells, and the characterization and differentiation of virus-specific memory T cell heterogeneity in mice and humans. Novel methods of visualization of immune cells and immune systems are reviewed in Section III. This includes tracking of dendritic cells in vivo, monitoring arterial smooth muscle-specific T cells in the inflamed vasculature, imaging of molecular migrations in immune synapses, and visualization of various immune cells in intact lymphoid tissues by two photon confocal imaging. This volume should be of interest to immunologists, molecular biologists, microbiologists, pathologists, academic physicians, cell bio

A remarkable spectrum of novel immunoreceptors sharing related immunoglobulin-like domains and signaling potential has been identified in recent years. These receptors have attracted widespread interest because they resemble the TCR, BCR, and FcR complexes in their ability to serve as activating or inhibitory receptors on the cells that bear them. Moreover, they are well positioned to affect both innate and adaptive immunity. The full range of ligands for these new receptor families is still not known, and understanding of their physiological roles is far from complete. This volume is the first attempt to summarize and highlight all known aspects of immunoglobulin-like receptors, providing a topical overview of the roles and characteristic features of the immunoglobulin-like receptors and related molecules in the immune system. Researchers in immunology, molecular biology, cell biology, clinical medicine, and pharmacology will find this book invaluable.

Highly experienced researchers describe in step-by-step detail methods that have proven most useful in delivering genes to mammalian cells. Volume 1: Nonviral Gene Transfer Techniques focuses on gene delivery by a variety of chemical and physical methods, including ultrasound, biolistics, peptides, PNA clamps, liposomes, microinjection, electroporation, particle bombardment, dendrimers, and hydrodynamics. An accompanying volume, Volume 2: Viral Gene Transfer Techniques, details procedures for delivering genes to cells in vitro and in vivo, including the use of lentiviral vectors.

This volume, new to The Receptors series, focuses on several areas, including the birth, maturation, and structure of Chemokines; Neutrophil, Dendritic, and Lymphocyte trafficking; and Chemokine Receptors in diseases such as AIDs and lung cancer. In particular the book contains cutting-edge information ranging from basic molecular and cellular mechanisms to physiological and pathological roles of chemokines.

Antibodies tagged with fuorescent markers have been used in histochemistry for over 50 years. Although early applications were focused on the detection of microbial antigens in tissues, the use of immunocytochemical methods now has spread to include the det- tion of a wide array of antigens including proteins, carbohydrates, and lipids from virtually any organism. Today, immunohistochemistry is widely used to identify, in situ, various components of cells and tissues in both normal and pathological conditions. The method gains its strength from the extremely sensitive interaction of a specifc antibody with its antigen. For some scientifc areas, books have been published on applications of immu- cytochemical techniques specifc to that area. What distinguished Immunocytochemical Methods and Protocols from earlier books when it was frst published was its broad appeal to investigators across all disciplines, including those in both research and clinical settings. The methods and protocols p- sented in the frst edition were designed to be general in their application; the accompa- ing "Notes" provided the reader with invaluable assistance in adapting or troubleshooting the protocols. These strengths continued to hold true for the second edition and again for the third edition. Since the publication of the frst edition, the application of immuno- tochemical techniques in the clinical laboratory has continued to rise and this third edition provides methods that are applicable to basic research as well as to the clinical laboratory.

Overall recent research on TLRs has led to tremendous increase in our understanding of early steps in pathogen recognition and will presumably lead to potent TLR targeting therapeutics in the future. This book reviews and highlights our recent understanding on the function and ligands of TLRs as well as their role in autoimmunity, dendritic cell activation and target structures for therapeutic intervention.

The aim of the former editions remains unchanged in the present updated version, namely to put forward a general and comprehensive review on complement. It is intended not only for individual investigators working in this specific field, but also for those who are less familiar with it. Students or younger scientists will hopefully be stimulated and attracted by the fascination of complement biology. Again, it was clear from the beginning that the field has experienced an explosive expansion in various directions and continues to accumulate data too large to be dealt with by a single author in a critical and coherent manner. The editors are grateful that the invited authors, all of them leading scientists in their field, helped again to make The Complement System a true mirror of the state of the art. Some parallels in the various chapters were accepted, as was a particular emphasis on newer developments in some chapters.

Immunochemical techniques have been in use for many years with early examples of bacterial strain typing dating back to the 1940s. The basis for the science is the exquisite elegance of the mammalian immune system with its ability to recognize foreign proteins and to manufacture antibody m- ecules that strongly bind to the substances that elicited them. Not only are potentially harmful pathogens and toxins recognized by the immune system, but the system can be persuaded to manufacture antibodies to an astonishing array of substances. In the early days of this science, all antibodies for investigative work were produced by immunizing mammals with the substance of interest, followed by regular donor bleeds that yielded antisera. Serum produced in this way yields heterogenic populations of antibody molecules recognizing different epitopes on the target protein, which may be adequate for its intended p- poses, but can also cause problems of crossreactivity. In 1975, Kohler and Milstein reported that spleen cells from immune donor animals could be immortalized, cloned from single cells, and grown in continuous culture. This original work described the method for the production of monoclonal antibodies.

A team of expert investigators and clinical researchers comprehensively review complement's basic biology, its role in disease, methods to measure its activity, and strategies for its inhibition in patients. Each chapter focuses on a specific area of basic and applied complement biology, spelling out the activation pathways and complement receptors. Informative animal models are discussed in detail, including the relative values of each model and the important interspecies differences that can distort the interpretation of preclinical studies. The emphasis throughout is on the pros and cons of the therapeutic use of recombinant complement inhibitors in specific diseases. Cutting-edge and innovative, Therapeutic Interventions in the Complement System highlights for today's researcher and biotechnologist effective strategies of drug discovery and development that are producing valuable new complement inhibitors for the treatment of a wide variety of clinically important diseases.

We have known about the existence of killer lymphocytes since 1960, when they were discovered in connection with transplant rejection in vivo. Since then we have uncovered at least five subsets of lymphocytes that can kill other cells in vitro, establishing the study of cell-mediated cytotoxicity (CMC) as a major field of immunological inquiry. Berke and Clark summarize the extensive literature based on the study of CMC in vitro. Several important questions about killer cells have now been answered, for example, how they go about destroying other cells. Research ultimately revealed at least three lytic mechanisms available to killer lymphocytes. But do killer cells actually use these mechanisms in vivo? The possible involvement of CMC in transplant rejection, control of intracellular parasites, cancer, autoimmunity, and immune homeostatic regulation is analyzed in detail, yielding some surprising findings, and outlining important questions that remain unanswered.

This extensively documented, comprehensive survey of cell-mediated cytotoxicity traces the history of killer lymphocytes from 1960 to the present, providing a definitive resource for specialists and non-specialists alike.

Immunofluorescence, a suitable laboratory method for the microscopic demonstration of antigens and antibodies in biological materials, useable, for example, to provide evidence for the pathogenesis of disease in histological or cytological preparations and for tumour cell differentiation. For this reason immunofluorescence has a decisive role as the method of choice for the diagnosis of auto-immune diseases. This primer on immunofluorescence techniques, which first appeared in 1979, is a richly illustrated handbook suitable for everyday practical work in the laboratory, useable as both an introduction to the subject as well as an atlas. In hardly any other area of medicine are there so many new findings to report. The second edition of this book is concerned not only with the detection methods which now form an essential and established part of diagnostic techniques, but also with the most recent research results such as the discovery of antibodies against Auerbach's plexus and against podocytes...

Although there have been many books on HIV and AIDS, surprisingly little has been published that focuses on the immunology of retroviral infections in general, and HIV in particular. Retroviral Immunology: Immune Response and Restoration is the first book of its kind to address the most important aspects of the immunology of retroviruses, including not only the virus-specific immune responses, but also genetic and virologic factors modulating these responses. The book also deals directly with the emerging concept of immune restora tion in retroviral infections, a particularly important subject to the thousands of clinicians who deal with this problem on a daily basis. With the advent of highly effective antiviral drug regimens to slow down the replication of HIV and the progression of AIDS, new challenges and opportunities are arising. Restoration of general immune function has brought with it not only complica tions of immune restoration-mediated disease, but also the realistic hope for meaningful restoration of the ability to control HIV replication with the immune system. Leading scientists in the field have summarized the most current informa tion regarding experimental and clinical aspects of retroviral infections. Retroviral Immunology: Immune Response and Restoration should prove an impor tant point of reference for basic scientists and clinicians in this area of research. We are indebted to all of our authors for their excellent contributions."

The current explosive progress in molecular biological research can be definitively traced to the development of molecular cloning technology. The ability to insert specific gene sequences into cloning vectors and their subse quent expansion is the cornerstone of modem molecular biology. A direct practical outcome of molecular cloning technology is its application to ex press specific recombinant genes. Currently, recombinant gene products are used in a wide spectrum of applications, including gene therapy, production of bioactive pharmaceuticals, synthesis of novel biopolymers, in agriculture and animal husbandry, and so on. A fundamental requirement for successful recombinant gene expression is the design of the cloning vector and the choice of the host organism for expression. Recombinant Gene Expression Protocols grows out of the need for a laboratory manual that provides the reader the background and rationale, as well as the practical protocols for the preparation of "expression constructs" and their introduction into appropriate host cells and/or organisms. The chap ters in this book are grouped by their expression hosts, including E. coli, yeast, mammalian cells, nonmammalian eukaryotes such as plants, Xenopus, and insects, as well as in transgenic organisms. In-depth information is presented on the important characteristics of expression cloning vectors and the various methods for efficiently introducing expression constructs into target cells and/ or organisms. Throughout Recombinant Gene Expression Protocols, the authors have consistently striven for a balanced presentation of both background informa tion and actual laboratory details.

The book provides up-to-date summaries on the main systems of blood group antigens and MHC molecules. The human systems are used to explain the necessary background knowledge and the systems in nonhuman primates are then described and compared. The emphasis is on the molecular nature of the gene products, the evolutionary relationships among the various systems, and the presumed mechanims by which the systems have evolved. All articles are written in such a way that they can serve as an introduction to the field for nonexperts and at the same time as a handbook for experts. Numerous tables, diagrams, and figures provide overviews of structure, distribution in different species, lists of known forms, and evolutionary relationships. Extensive reference lists guide the reader through the literature on each topic.

The number of investigators focusing their attention on lactoferrin has increased dramatically in recent years. Lactoferrin is a protein with more than one known structure and a number of proposed biological functions, including several with important regulatory consequences. In many ways it has been an easy pro tein to investigate; however, there have been difficulties under standing specific structure / function relationships, particularly as it functions in vivo. Research funding dedicated to this protein has previously been limited, but is now increasing. As lactoferrin begins to emerge formally as a protein of significance to the medi and industry, it is more important than ever to coor cal profession dinate and integrate research efforts whenever possible and to share the results of these efforts within the expanding array of medical and scientific diSciplines involved. It was our intention to provide a forum to summarize and disseminate the most recent advances in this field. Included in Lactoferrin: Interactions and Biological Functions are selected presentations representing the many disciplines involved in defining lactoferrin function in terms of its known structural features, including its carbohydrate side-chains, receptor binding sites, its capacity to bind different metal ions, and other newly discovered bioactive domains. Several of the possible physiologi cal functions of lactoferrin are described and summarized in detail, including the role of laetoferrin in bacterial killing, its in volvement in cell growth and proliferation, in the modulation of immune function, and in iron absorption."

Most complex biological systems, such as enzyme pathways, are effec tively controlled near the beginning of the process. There is increasing evidence that the same is true for the immune system, with the initial interactions between antigen, antigen-presenting cells, and T cells hav ing a paramount influence on the ensuing events. Thus, analysis of the early stages of the immune responses has been a preoccupation of many immunologists. This has been considerably aided by the capac ity to expand these early events, and 'immortalize' them as clones of T cells, for detailed analysis. The discovery by Morgan, Ruscetti, and Gallo (Science 193, 1007, 1976) of T-cell growth factor (now termed interleukin-2 or IL-2) has had a major impact in immunology that is far from over. The greater ease of handling murine tissues experimentally, with the availability of more precisely defined reagents such as inbred strains, has meant that, to date, most of the work on long-term T-cell cultures has been per formed in the mouse, as summarized by Fathman and Fitch (eds., Iso lation, Characterization and Utilization of T Lymphocyte Clones, Aca demic Press, NY, 1982). However, the limitations of working with human tissues are counterbalanced by the great long-term importance of understanding disorders of human immune regulation, especially since it is becoming evident that these are far from rare. Immune deficiencies such as agammaglobulinemia and T-cell deficiencies are not common, but immune hyperresponsiveness occurring in allergy and allergiC diseases (e. g."