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.

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.

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

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.

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...

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.

This fascinating intellectual history is the first critical study of the work of Elie Metchnikoff, the founding father of modern immunology. Metchnikoff authored and championed the theory that phagocytic cells actively defend the host body against pathogens and diseased cells.

In this scientific biography, Tauber and Chernyak explore Metchnikoff's development as an embryologist, showing how it prepared him to propose his theory of host-pathogen interaction. They discuss the profound impact of Darwin's theory of evolution on his progress, and the influence of 19th century debates on vitalism, teleology, and mechanism. As a case study of scientific discovery, this work offers lucid insight into the process of creative science and its dependence on cultural and philosophic sources.

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 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."

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.

The purpose of the preface is to explain the book's objectives and how to use it; give warnings, disclaimers, and the like.* The main objective of Protein and Peptide Analysis by Mass Spec trometry is quite straightforward-to present authoritative, up-to-date, and practical accounts of the use of mass spectrometry in the analysis of pep tides and proteins. How to use it? Every reader will have their own particular interests and will surely be drawn toward the chapters that cover these interests. Within the remaining chapters, however, techniques are described with analytical possibilities that such a reader can then only guess at. So, read the book fully. Again, as is customary in the Methods in Molecular Biology series, the chapter format (Introduction, Materials, Methods, and Notes) allows the authors to introduce the techniques, to explain their relevance and applicability, and, above all, to provide detail-detail that represents each author's accumulated experience and enables the reader to use and benefit from these methods. So, read the book fully, and read it diligently. Warnings and disclaimers: Mass spectrometry today offers the pro tein chemist ready access to a wealth of information that is otherwise avail able only with great difficulty, or perhaps not at all. With this goal in sight, any warnings and disclaimers will almost surely be ignored. So, a warning anyway; the use of mass spectrometry might be habit forming."

This authoritative volume examines immunohistochemical methods aimed at investigating the toxicologic pathology of rodent, non-human primate and aquatic animal tissues. Eleven comprehensive chapters provide pathologists and researchers in various sub-disciplines of toxicology with a comprehensive review of the methods and approaches for immunohistochemical staining in various target tissues. It explores the tissue-antigen and antibody-specific problems that may be encountered during the staining procedures and provide potential avenues for resolving various methodological issues. Special attention is paid to the latest enhancement procedures for antigen retrieval and visualization as well as image analysis and antigen quantification. Written by leading researchers in toxicology and pathology, this book is a significant resource for toxicologists and pathologists working with rodents, monkeys and aquatic animal tissues.

This book contains the proceedings of the first meeting on invertebrate immunity ever sponsored as a summer research conference by the Federation of American Societies for Experimental Biology (FASEB). The conference was held in Copper Mountain, CO from July 11-16, 1999. It was a an extension of a New York Academy of Sciences meeting entitled "Primordial Immunity: Foundations for the Vertebrate Immune System" held on May 2-5,1993 at the Marine Biological Laboratories in Woods Hole, MA. The proceedings of that meeting were published in The Annals of the New York Academy of Sciences (volume 712). At that meeting all the attendes agreed that this type of conference (a relatively small focused gathering) allowed for participation by investigators at all levels of their careers. We further agreed that we should search for a forum that would allow this meeting to continue. The FASEB Summer Research Conference was an excellent vehicle for this type of meeting. Furthermore, this year's participants decided to continue this meeting as a regularly scheduled FASEB sponsored event. This was a unique conference in the sense that it focused upon mechanisms of development and defense in protostome and deuterostome invertebrates and lower vertebrates. There was a strong emphasis on evolutionary cell biology, phylogenetic inferences and the evolution of recognition and regulatory systems.

Contents:
1. Bacterial and Plant Toxins - General Mode of Action A.E. Frankel and P.D. Hall 2. Diphtheria Toxin-Structure, Function and its Therapeutic Use R.C. Ratts and J.C. VanderSpek 3. Ricin A-Structure, Function and its Clinical Applications M. Colmbatti 4. Pathways of Delivering Toxins into the Cytosol of Target Cells M. Lord, P.J. Day, M.E. Jackson, S.R. Owens, J.C. Simpson, D.C. Smith and L.M. Roberts 5. Engineering Immunotoxins for Improving their Therapeutic Activity Y. Reiter, G. Denkberg and C. Cohen 6. Ligand-receptor Interactions Studied with Chimeric Proteins H. Lorberboum-Galski 7. Chimeric Proteins: a Novel Approach for Eliminating Specific Cell Populations for Targeted Human Therapy A. Ben-Yehudah, R. Belostotsky, R. Aqeilan, Y. Azar, I. Steinberger, A. Fishman, A. Nechushtan, S. Yarkoni and H. Lorberboum-Gaski 8. Chimeric Neurotoxins - a Molecular Neurosurgery Approach P. Lazarovici 9. Targeted Immunotherapy of Autoimmune Diseases by Chimeric Toxins B.A. Holder and J.G. Krueger 10. Immunotoxins for Targeted Cancer Therapy R.J. Kreitman 11. Molecular Targeting of Brain Tumors with Cytotoxins W. Debinski 12. Toxins in the Development of Vaccines C.T. Hsu, C.Y. Ting and J. Hwang

This volume presents a collection of reviews derived from work presented at the Aegean Conference: "4th Crossroads between innate and adaptive immunity". This meeting was the fourth 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 something necessary for 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. The conference had limited participation and a scientific and social program that maximized scientific interchange through lecture presentations, poster sessions and informal discussions.

This volume is devoted to the application of microorganisms in medical treatment and health protection. Topics discussed include the role of probiotics in immune modulation, in prevention of influenza, and in atopic dermatitis. Further chapters cover aspects such as the relation of the gut microbiome and stress, the immune system, the regulation of inflammation, the benefits of Bifidobacterium for infants, and bacteriocin in medical applications, as well as the use of in vitro models of the gastrointestinal tract, omics approaches for targeting microbial health potential and the production of hepatitis B vaccines. This volume will be of particular interest to scientists working in the fields of clinical medicine, applied microbiology, pharmacy and public health.

Provides a detailed survey of new therapies for autoimmune diseases, exploring the rationale for their use and clinical data regarding their potential benefit. The book emphasizes biological interventions based on the pathogenesis of autoimmunity, ranging from altering tolerance to modifying cytokines and changing lymphocyte function.

Handbook of HLA Typing Techniques is an authoritative collection of HLA phenotyping and genotyping techniques to be used at the bench level and as a reference. The information presented, much of it previously unpublished, was written by leading authorities in the field of transplantation. Each chapter provides detailed methodologies, notes on the interpretation of tests, reference material, and appendices.

Phenotyping topics covered include microlymphocytotoxicity assay, monoclonal antibodies, complement testing, serum screening for HLA antibodies, lymphocytotoxic crossmatching, and mixed and primed lymphocyte testing. Genotyping topics discussed include well-established RFLP analysis and polymerase chain reaction applications of PCR-SSO, PCR-RFLP, PCR-SSP, and PCR fingerprinting and related DNA heteroduplex technologies. Handbook of HLA Typing Techniques is an indispensable sourcebook for all researchers, practitioners, and students in the international tissue typing and human immunogenetics community.

The localized attachment of circulating leukocytes to endothelium has been recognized as the cellular hallmark of the inflammatory response. This adhesive interaction, a necessary antecedent to the emigration of leukocytes from the blood into the tissues, is mediated by vascular adhesion molecules. Leukocyte Recruitment, Endothelial Cell Adhesion Molecules and Transcriptional Control: Insights for Drug Discovery outlines some of the cellular and molecular mechanisms of inflammation with contributions from top researchers. This volume provides an overview of three of these endothelial adhesion molecules, as examples of key mediators of leukocyte recruitment. It reviews the structure and regulation of these cell surface proteins and focus on the rapidly expanding field of transcriptional regulation of these inducible proteins, and closes with a discussion of drug discovery possibilities that target the regulation of leukocyte recruitment. This book will be of interest for any researchers, in academia or industry, looking for an overview of leukocyte recruitment or novel approaches to drug discovery.