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The student of biological science in his final years as an undergraduate and his first years as a graduate is expected to gain some familiarity with current research at the frontiers of his discipline. New research work is published in a perplexing diversity of publications and is inevitably con­ cerned with the minutiae of the subject. The sheer number of research journals and papers also causes confusion and difficulties of assimilation. Review articles usually presuppose a background knowledge of the field and are inevitably rather restricted in scope. There is thus a need for short but authoritative introductions to those areas of modern biological research which are either not dealt with in standard introductory textbooks or are not dealt with in sufficient detail to enable the student to go on from them to read scholarly reviews with profit. This series of books is designed to satisfy this need. The authors have been asked to produce a brief outline of their subject assuming that their readers will have read and remembered much of a standard introductory textbook of biology. This outline then sets out to provide by building on this basis, the conceptual framework within which modern research work is progressing and aims to give the reader an indication of the problems, both conceptual and practical, which must be overcome if progress is to be maintained.

This highly readable textbook serves as a concise and engaging primer to the emerging field of antibody engineering and its various applications. It introduces readers to the basic science and molecular structure of antibodies, and explores how to characterize and engineer them. Readers will find an overview of the latest methods in antibody identification, improvement and biochemical engineering. Furthermore, alternative antibody formats and bispecific antibodies are discussed.The book's content is based on lectures for the specializations “Protein Engineering” and “Medical Biotechnology” within the Master's curriculum in “Biotechnology.” The lectures have been held at the University of Natural Resources and Life Sciences, Vienna, in cooperation with the Medical University of Vienna, since 2012 and are continuously adapted to reflect the latest developments in the field. The book addresses Master- and PhD students in biotechnology, molecular biology and immunology, and all those who are interested in antibody engineering.

Volume Immunodeficiency Diseases in Springer's gold-standard reference work on medical immunology focuses on infectious diseases. In tandem with its three counterpart volumes it offers the most wide-ranging and authoritative repository of knowledge on infectious diseases, with readily accessed contributions by the world's leading authorities on the subject. The encyclopedia covers the material from all angles, with more than 1000 pages of essays on the genetics, physiology, metabolism, pathogenesis and applied microbiology of all known infectious diseases, and includes access to an e-reference work that will include ongoing updates reflecting the latest advances in the field.An outstanding new resource of immense value to a wide range of medical researchers and practitioners, the encyclopedia features a user-friendly subdivision of diseases according to their affective locus in the human body. The sections cover integumentary, skeletal, respiratory, digestive, urinary, and reproductive transmissible pathogens. This high-profile encyclopedia will be an essential addition to academic libraries worldwide.

This volume explores several aspects of how antibodies mediate their activity in vivo, ranging from cancer immunotherapy to autoimmunity, infection, and vaccination. Divided into seven chapters, it provides in-depth insights into how antibodies and especially the antibody fragment crystallizable (Fc) domain modulate immune responses and antibody activity. The book begins by discussing evolutionary aspects of how the family of Fc receptors that are the key molecules for antibody activity evolved. In turn, it addresses the molecular and cellular pathways underlying IgG activity in cancer immunotherapy, and focuses on how IgG glycosylation regulates IgG and IgE activity in autoimmunity, allergy and infection. In closing, it presents strategies for developing novel antibody-based vaccination approaches. The book is intended for a very broad readership, including graduate students, postdocs and principal investigators with a basic grasp of immunology.

This volume examines all facets of the complex biology of Immunoglobulin E (IgE) antibodies, which play an essential role in the pathophysiology of allergic diseases and immunity to parasites. It highlights the unique mechanisms involved in the regulation of IgE production at both the molecular and cellular level. Furthermore, it discusses in detail novel findings on how the affinity, specificity and cross-reactivity of IgE can fine-tune mast cell responses to allergens. The book also explores the beneficial roles of IgE antibodies in immunity to helminthes and protection against tumors, and how the properties of IgE-mediated immunity are employed in the development of IgE therapeutic antibodies. All chapters were written by respected experts in their fields and will appeal to scientists and clinicians alike.

This book focuses on the function of antibodies in vivo. Recent years have seen an exponential growth in knowledge about the molecular and cellular mechanisms of antibody activity. These new results dramatically changed our view of how antibodies function in vivo. The importance of this class of molecules is demonstrated by the heightened susceptibility to infections of humans and mice with an altered capacity to generate pathogen specific antibody responses. Thus, the majority of our currently available vaccines, such as vaccines against influenza, measles and hepatitis focus on the generation of long lasting antibody responses. Recent evidence from a variety of in vivo model systems and from human patient cohorts has highlighted the exclusive role of cellular Fc-receptors for certain immunoglobulin isotypes and subclasses. With the recent discovery of a human Fc-receptor for IgM all different human immunoglobulin isotypes now have a cellular receptor, providing a feedback mechanism and link between antibodies and the cellular components of the immune system. Moreover it has become clear the complement and Fc-receptor system are tightly connected and regulate each other to ensure a well balanced immune response. Among the immunoglobulin isotypes IgG plays a very important protective role against microbial infections and also as a therapeutic agent to kill tumor cells or autoantibody producing B cells in autoimmune disease. Transfer of our knowledge about the crucial function of Fc-receptors has led to the production of a second generation of therapeutic antibodies with enhanced binding to this class of receptors. Binding of antibodies to Fc-receptors leads to the recruitment of the potent pro-inflammatory effector functions of cells from the innate immune system. Hence, Fc-receptors link the innate and adaptive immune system, emphasizing the importance of both arms of the immune system and their crosstalk during anti-microbial immune responses. Besides this pro-inflammatory activity immunoglobulin G (IgG) molecules are long known to also have an anti-inflammatory function. This is demonstrated by the use of high dose intravenous immunoglobulins as a therapeutic agent in many human autoimmune diseases. During the past five years several new insights into the molecular and cellular pathways of this anti-inflammatory activity were gained radically changing our view of IgG function in vivo. Several lines of evidence suggest that the sugar moiety attached to the IgG molecule is responsible for these opposing activities and may be seen as a molecular switch enabling the immune system to change IgG function from a pro- to an anti-inflammatory activity. There is convincing evidence in mice and humans that aberrant IgG glycosylation could be an important new pathway for understanding the impaired antibody activity during autoimmune disease. Besides this tremendous increase in basic knowledge about factors influencing immunoglobulin activity the book will also provide insights into how these new insights might help to generate novel therapeutic approaches to enhance IgG activity for tumor therapy on the one hand, and how to block the self-destructive activity of IgG autoantibodies during autoimmune disease on the other hand.

When the history of immunology in the twentieth century is written, the decade of the 1960's will, in all probability, stand out as the period of greatest advance in the development of molecular immunology. It is appropriate and useful, therefore, that a schol­ arly and integrated presentation of this progress should be made available in English. The translation of Dr. Nezlin's'Biochem­ istry of Antibodies'from Russian admirably fulfills this need in the form of a scientific monograph directed to medical and biolog­ ical scientists. The appearance of this monograph also serves to emphasize the conceptual unification of diverse immunological phenomena which has emerged from progress in molecular immunology. This unity is a consequence of the key role played by the antibody mol­ ecule (either in solution or cell-bound) in every biological process properly described as immunological. Indeed, immunology as an independent natural science can be described as the study of the structure, interactions, and biosynthes is of the antibody molecule.

Rapid advances continue to be made in all areas of immunology, not least the biology of the immunoglobulins. This knowledge has resulted in a better understanding of antibody responses and helped to clarify pathogenic mechanisms in many diseases, particularly autoimmune and allergic diseases, as well as expand our comprehension of antibody deficiency diseases and mechanisms in therapeutic immunization. In addition, the recognition that diverse disease states may result in abnormalities of the amount of immunoglobulins in body fluids has resulted in the use of immunoglobulin assays for disease diagnosis and management. The aim of this book has been to condense both the established and recent aspects of this knowledge, particularly that pertaining to clinical immunology. The contributions of different authors hopefully provide a comprehensive review of their particular field of interest as well as a discussion of how this information can be applied to clinical medicine. Immunological terms and concepts have been explained where appropriate so that the book can be read by those with only a basic knowledge of immunology. In producing a book on this one area of immunology some duplication of information has been accepted so that topics can be considered in different contexts. I hope the book will be of value to those in training or already pursuing a career in clinical or laboratory medicine by providing a basic and short text on immunoglobulins. M.A.H.F.

Since the discovery more than thirty years ago that antibody actlvlty could be localized to discrete plasma protein fractions, the study of immunoglobulin struc­ ture and function has dominated the field of immunochemistry. During this time, sources of homogeneous immunoglobulin molecules have been discovered, the subunit nature of the proteins has been defined, and the three-dimensional struc­ tures of the antigen-recognition portion of several antibody molecules have been elucidated. Insights into the complicated genetic control of these proteins are being gained rapidly through analysis of amino acid sequences of naturally occurring and induced homogeneous immunoglobulins. Immunoglobulins have been analyzed by protein chemists as models of complex multimeric systems, examined by geneticists studying serum protein polymorphisms, and employed by molecular biologists as highly selective probes capable of distinguishing minor features of molecular topog­ raphy. Clinical applications have ranged from the now routine quantitation of immunoglobulin levels to the use of antibodies to detect trace levels of a variety of natural products and drug metabolites. All these applications have depended ulti­ mately on a thorough understanding of the immunoglobulin and its antigen-combin­ ing site. To cover the entire field of immunoglobulin structure and function would require many volumes this size; therefore, subjects presented in this volume represent those which we felt contribute most to our current understanding of this protein family. The first chapters deal with the structure and function of the immunoglobulin molecule.

The ever-expanding research on human cancer has resulted in numerous technical and conceptual advances during the last few years. Serological, structural, and biological char­ acterization of human melanoma constitutes one area of research that has received consid­ erable attention from researchers and clinicians and has generated new and exciting infor­ mation. In this volume, we have attempted to assemble work on topics that produced some of the most recent advances. We asked each author to describe and interpret his most cur­ rent research and, whenever possible, to compare and contrast it with work of other inves­ tigators in the field. We have been careful not to impose our viewpoints except in contri­ butions from our own laboratories, since we want to provide the reader with as many divergent and sometimes opposing viewpoints as feasible. Therefore, we have not been overly concerned with overlaps in some individual topics. We hope that this volume will provide the reader with a well-balanced overview of current problems and ideas in a par­ ticular area of cancer research. We wish to express our thanks to all contributors for their timely and very interesting manuscripts, and we sincerely hope that the reader will enjoy this volume and benefit as much from it as we did. R. A. Reisfeld S. Ferrone La Jolla ix Contents CHAPTER 1 Immunogenetics of Melanoma RONALD T. ACTON, CHARLES M. BALCH, BRUCE BUDOWLE, RODNEY C. P. Go, JEFFREY M. ROSEMAN, SENG-jAW SOONG, AND BRUCE O. BARGER 1. Introduction.........................................................

Many pathogens and aberrant malignant cells express unique carbohydrates on their surface representing attractive targets for vaccine design. Considerable progress has recently been made in the identification of novel carbohydrate based vaccines and a large number has reached clinical phase studies. The success of several licensed carbohydrate based vaccines against bacterial pathogens such as Haemophilus influenzae type b, Neisseria meningitidis or Streptococcus pneumoniae demonstrates their great potential. However, the study of anti-carbohydrate antibodies is technically challenging and partly because of low affinities and promiscuous specificity they have not been medically exploited to full potential. The study of antibody specificities and identification of protective carbohydrate epitopes lies at the heart of successful vaccine design. In addition to therapy, antibodies in general serve as diagnostic tools in medical and scientific laboratories. In this setting high affinity and exquisite specificity are important factors for their successful use. “Anticarbohydrate Antibodies – from molecular basis to clinical application” compiles current knowledge on the immunological recognition of carbohydrates by the adaptive immune system from a molecular perspective providing fundamental insight needed for advancing clinically relevant diagnostics and therapeutic applications. Based on significant progress in the fields of glycoimmunology and structural biology in recent years, the book comprehensively reviews the state-of-the-art in defining the key elements of carbohydrate recognition by antibodies, the molecular mimicry of carbohydrate epitopes as well as the molecular features leading to specific and relaxed binding modes. Backed-up by a combination of modern technologies to elucidate structural details of carbohydrate-antibody interactions, biomedically important carbohydrate antigens from viral, bacterial, parasite, insect and tumor cells have beenanalyzed in in-depth reviews written by well-known experts in the field. Fundamental knowledge of these molecular mechanisms eventually provides a rational basis to improve efficacy of carbohydrate-based vaccines and to further refine diagnostic tools in detection of pathogens and malignant cells.

This volume illustrates the functional properties of NAbs. Authors from pioneering groups report in their chapters on the tissue homeostatic, tissue regenerating and regulatory properties of NAbs and NAbs in pooled human IgG. Scientists interested in the regulation and modulation of components of the immune system found a whole variety of NAbs to cytokines with regulatory and protective functions and NAbs that modulate, e.g., dendritic cells, regulatory T cells, B cells and granulocytes. Considering the large plasma pools and initial difficulties in preparing IVIG that does not induce adverse effects upon infusion into recipients, this volume ends with a historical chapter on how pooled human plasma was fractionated and the IgG component pretreated for a safe intravenous application.