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 50th volume in a monographic series on immunology. Among the topics covered here are avian T-cell ontogeny, adoptive transfer of human lymphoid cells to severely immuno-deficient mice and histamine-releasing factors and cytokine-dependent activation of basophils and mast cells.

This unique book provides a comprehensive and comparative guide to the immune systems of major vertebrate species, including domestic and wild animals of veterinary or medical interest, fish and amphibia. Data in this essential reference work has been compiled by world-renowned editors and an international group of authors. For each species, the information is presented in a structured 'user-friendly' format allowing easy cross reference and comparison between the various species.
This book will be considered the definitive reference work on vertebrate immunology and will be essential for scientists and professionals working in Immunology, Vaccinology or with Animal Models, for students of Veterinary or Human Medicine, Biology and researchers in Comparative Medicine and Physiology.
Each section, devoted to a major animal group covers:
* Lymphoid organs and their anatomical disposition
* Leukocytes and their markers
* Leukocyte traffic and associated molecules
* Cytokines
* T cell receptors
* Immunoglobulins
* MHC antigens
* Ontogeny of the immune system
* Passive transfer of immunity
* Neonatal immune responses
* Non-specific immunity
* Complement system
* Mucosal immunity
* Immunodeficiencies
* Tumours of the immune system
* Autoimmunity

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.

How do you keep track of basic information on the proteins you work with? Where do you find details of their physicochemical properties, amino acid sequences, gene organization? Are you tired of scanning review articles, primary papers and databases to locate that elusive fact?
The Academic Press FactsBook series will satisfy scientists and clinical researchers suffering from information overload. Each volume provides a catalog of the essential properties of families of molecules. Gene organization, amino acid sequences, physicochemical properties, and biological activity are presented using a common, easy-to-follow format. Taken together they compile everything you want to know about proteins but are too busy to look for. The Chemokine FactsBook contains more than 40 entries on chemokines, and chemokine receptors from human or other origin, including IL-8, MCP-1, C5-a, RANTES, Lymphotactin, and CC CKR-1.
The text provides information on tissue sources, target cells, physicochemical properties, transcription factors, regulation of expression in disease, receptor-binding characteristics, gene structure and location, amino acid sequences, and accession numbers and references.
Key Features
* Contains over 40 entries on chemokines and chemokine receptors from human or other origin, including:
* IL-8
* MCP-1
* C5-a
* RANTES
* Lymphotactin
* CC CKR-1
Entries provide information on:
* Tissue sources
* Target cells
* Physicochemical properties
* Transcription factors
* Regulation of expression
* Expression in disease
* Receptor-binding characteristics
* Gene structure and location
* Amino acid sequences
* Database accession numbers
* References

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...

Immunology has progressed in spectacular fashion in the last four decades. Studies of the response to infectious agents, transplanted organs and tumours (and the potential to manipulate that response), and the study of the immune system as a model system in molecular cell biology have yielded dramatic advances in our understanding of the mechanisms of immunity.
The field has attracted a continuous stream of the brightest theoretical and experimental scientists for over forty years. This book conveys the philosophies and approaches of sixteen of the most successful of these scientists in the form of a series of narratives that describe the circumstances that led to a major discovery in immunology. Contributors not only recall an exciting period of research that helped shape modern immunology, but set it in the personal context of place and time. Jacques Miller, for example, describes the discovery of the function of the thymus, Rolf Zinkernagel explains how experiments on viral immunity led to the discovery of MHC restriction and Susumu Tonegawa provides an account of how antibody gene structure was defined. Medically-important discoveries include descriptions of early studies of autoimmunity by Noel Rose and of tumour immunology by George and Eva Klein.
Far from being a collection of disinterested, historical accounts, this volume comprises a series of passionately biographical, personal essays that provide an unusually intimate insight into the scientific process. This book will be essential, and fascinating, reading for all those with an interest in immunology, and in the life sciences in general. For students and teachers, this will provide the background necessary for a true understanding of immunology, and to place subsequent discoveries in perspective.

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.

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."

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."

Morphological, physiological and pathological evidence demonstrates that ner- vous and immune systems interact not only in maintaining brain homeostasis, but also in causing neurological diseases. The studyofthese interactions repre- sents the basis on which neuroimmunologyhas grown during the years. At pre- sent, several neurological diseases are recognized to be caused by a derange- ment of the immune system in either its regulatory or effector functions. The main scope ofthis book, to discuss how an unbalanced immune system maylead to immune-mediated neurological diseases, is achieved in three parts. The first part provides an overview on how the immune system works. This is propaedeutical to understanding interactions between the immune and ner- vous systems, which are discussed in the second part. The third part of the book focuses on one particular area of neuroimmunology, the immune disor- ders leading to the damage of central and peripheral myelin. Given the opportunity to review first the immune system in itself and then how it operates during immune-mediated demyelinating disorders, we have tried to provide the reader with a basis for clearly understanding how interac- tions between the immune and nervous systems can be protective or pathoge- nic. This knowledge is a prerequisite for a rationale immune intervention tar- geting these disorders.

Protein glycosylation is now acknowledged as a major posttranslational modification with significant effects on protein folding, conformation distri- bution, stability, and activity. The added oligosaccharide chains are large and diverse and have specific recognition motifs important in many aspects of cell interactions and regulation. As such, there is a growing need to communicate the analytical methods of the specialist carbohydrate chemist, biochemist, and physicochemist to protein experts and the pharmaceutical industry. Other areas that come under the influence of the glycosciences are DNA interactions with ubiquitous saccharide-containing antibiotics and antitumor drugs; inhibitors of viral infection; bacterial, mycobacterial, and parasite antigens; glycolipids; glycophosphatidylinositol protein membrane anchors; and (glyco)protein- proteoglycan interactions. Compared to the first edition of this book, Glycopro- tein Analysis in Biomedicine, less emphasis is given to biomedical aspects, but these chapters are still pertinent today. The significant differences in the con- tent relate to advances in analysis relevant to biotechnology; for example, the production of recombinant glycoproteins and other therapeutics. It must also not be forgotten that the methods here described in Glycoanalysis Protocols are relevant to exploiting the commercial potential of carbohydrates in fields related to agriculture, food, and the domestic and chemical industries. The emphasis of the book remains in bringing the glycosciences into mainstream biochemistry. The analytical methods covered in Glycoanalysis Protocols are the re- sult of experts translating their life's works into easy-to-follow recipes.

This book is the first comprehensive volume on the "Nramp family," highlighting the physiological importance of Nramp proteins as metal transporters. The molecular knowledge of these membrane proteins is presented from an evolutionary perspective, considering Nramp cellular function and mechanism of transport in key model organisms. The pathological significance of Nramp genetic polymorphism is discussed with emphasis on metal homeostasis and microbial infection. The chapters were contributed by leading investigators, providing a timely state of the art book in this rapidly growing field.

The Nramp Family will be useful to a broad community of scientists interested in metal transport and molecular biology. It will be of interest to the research audience in the broad fields of metal ions and molecular medicine.

Antigen processing and presentation, as a field, explores a broad range of protein interactions and functions, both intracellular (in the cytoplasm and in the endoplasmic reticulum) and at the cell surface (between T cells and MHC molecules). To investigate such a diverse array, it is necessary that biochemical, cell biology, and immunological techniques all be employed. The purpose of Antigen Processing and Presentation Protocols is therefore to detail the most up-to-date techniques being used in this burgeoning field. Such techniques include those used to question how MHC-binding peptides are generated, to test how peptides are delivered to MHC molecules, to analyze MHC peptide-binding patterns, and to assay the T-cell response to MHC/peptide. Antigen Processing and Presentation Protocols should aid both those new and those experienced in this area of research in extending the questions that can be asked and answered by the application of these current methods. For editorial assistance, I would like to thank Angela Beninga and Rachael Turnquist.