Proper development and differentiation of B lymphocytes is es sential to ensure that an organism has the ability to mount an effective humoral immune response against foreign antigens. The immune system must maintain a balance between the deletion of harmful self-reactive B cells and the generation of a diverse rep ertoire of B cells that has the ability to recognize an almost un limited array of foreign antigens. The need to delete self-reactive cells is tempered by the need to avoid the generation of large functional holes in the repertoire of foreign antigen-specific B cells that patrol the periphery. To accomplish this, the immune system must reach a compromise by eliminating only the most dangerous autoreactive clones, while allowing less harmful au toreactive B cells to exist in the periphery where they may com plement the organism's ability to mount a rapid response against invading micro-organisms. Those autoreactive cells that do enter the peripheral pool are subject to a number of conditional re straints that effectively attenuate their ability to respond to self antigens. Deleterious alterations in the homeostasis between tolerance induction and recruitment of B cells into the functional repertoire may lead to increased susceptibility to autoimmune disease or infection, respectively. Therefore, delineation of the molecular processes that maintain immunological homeostasis in the B cell compartment is critical."

Today, advances in the area of immunology and breast cancer are made at an increasing rate, yielding an amount of information that can become unwieldy. The opportunity for scientists in this area of research to gather together to exchange results and working hypotheses represents, in my belief, a very attractive proposition. With this in mind, these workshops have been convened with two year intervals for the last ten years. In each of them, selected topics have been highlighted. The present workshop underscores the large advancements made in the molecular biology of both breast cancer associated antigens and their corresponding antibodies. Understanding the genetic information for the expression of these antigens has been recently advanced leading to preparation of molecularly engineered reagents for use in vaccination, serum assays, and immunizations for novel antibody production. In the anti-breast cancer antibody field the availability of molecular engineering approaches to humanize murine antibodies has induced intense interest in the creation of less immunogenic antibody forms that are now available for clinical testing. Clinical studies using anti-breast murine antibody continue to be carried out and are presented at this meeting establishing a base line for safety and efficaciousness in imaging and immunotherapy that it is hoped will be superseded by the humanized forms. Basic immunology and immunochemistry studies in breast cancer are also included in this workshop that demonstrate the fast pace at which this research is advancing in many laboratories worldwide.

Scientists and clinicians attending the last "New Directions in Antiviral Therapy" conference in late 1994 could hardly have predicted the revolution in the management of patients with HIV infection that has occurred since. Two new classes of antiretrovirals have been licensed, the second-site RT inhibitors and the protease inhibitors; the long in cubation period of active HIV infection, when the infection is clinically latent, is now un derstood to be a period of intense viral replication and turnover of CD4 lymphocytes; measurements of HI V RNA concentration in plasma have been shown to be essential tools for monitoring the course of HIV infection, deciding when to treat, and assessing the re sults of treatment; and finally, combinations of antiretrovirals, particularly combinations including protease inhibitors, have been shown to have dramatically beneficial effects on patients with HIV infection. These advances, coupled with new drugs for the management of herpesvirus infections, have made dramatic differences in the quality and length of life of HIV-infected patients. Additional advances have been made since 1994 in the prevention or management of influenza virus (zanamavir), respiratory syncytial virus (palvizumab), hepatitis B virus (lamivudine and famciclovir), and enterovirus infections (pleconaril). It is difficult to re member that only slightly more than a decade ago there were only a handful of antiviral agents available (none of which were antiretrovirals), and a number of those were either highly toxic, of dubious efficacy, or both."

The immune system has evolved in large part to enable organisms to resist microbial infeetion. Given this very fundamental relationship between the immune system and infeetious microbial agents it is entirely appropriate that avolume in this series should be devoted to the immunology of infeetion. Mieroorganisms have long been used as experimental tools by immunologists, and the study of the immune response to viruses and baeteria has eontributed mueh to our understanding of basie immunologieal meehanisms (for example of the meehanism by whieh non-self determinants on eells are reeognized). However there are of eourse important praetieal and elinical reasons for attempting to understand the immunology of infeetions - these inelude the needs for rational design of vaeeines and to understand the pathogenesis of human infeetious diseases. The last deeade or so has seen a resurgenee of interest in infeetious diseases and a reeognition that they remain of importanee and pertinenee to all areas of medicineo This is not just beeause of the advent of AIDS, although that has been a major faetor - the rise in drug-resistant myeobaeterial infeetions and the reeognition of the infeetious aetiology of peptie uleer disease are other illustrations. It should be made elear that this volume deals with aspeets of the immunolgy of baeteria, viruses and fungi - but it does not deal with parasite immunology which it is planned to eover in a separate volume in the series.

Immunosuppression in solid organ transplantation is currently experiencing a worldwide revival since new drugs are now available and others are under development. In order to contribute to the design of future strategies, a critical approach of surrogate endpoints is given and long-term side effects are analysed, together with the impact of non-compliance, quality-of-life and economical parameters. In this book, international specialists have set up the scientific rationale and provided new bases for further immunosuppressive strategies.

Physiological, pharmacological and molecular biological data generated over the past three decades have demonstrated the existence of two major families of extracellular receptors, the P1, a family of four G-protein coupled receptors and the P2, a family of at least 12 receptors responsive to purine (ATP, ADP) and pyrimidine (UTP) nucleotides through which adenosine and ATP can function as extracellular messengers. The present two-part volume represents an integrated compendium of invited chapters by leading researchers in the area focusing on advances in the understanding of purinergic and pyrimidinergic signaling systems, their role(s) in tissue function and pathophysiology and advances in developing potential new medications based on the modulation of P1 and P2 receptor signaling processes. The volumes will thus provide the reader with a topical, comprehensive and integrated overview of this important area.

The term "autoimmunity" has been used to categorize a number of different diseases of unknown etiology. The term as applied to many of these diseases would probably be interpreted best as "autoreactivity," as the clinical phenotypes are often characterized by an inflammatory-like accumulation of activated cells of the immune system at sites of obvious damage of normal cells and/or tissue. The reasons as to why an immune system should attack itself are far from clear, although the association with specific infectious diseases in genetically susceptible people remains perhaps our best lead. The input of the biotechnological revolution has enabled us to attempt to readdress many of the fundamental questions raised by clinical and serological associations with autoimmune disease. The ability to dissect the immune response to these infectious agents which are associated with autoimmune features (as well as the facility to identify new agents, e. g. HIV), in addition to the ability to clone and sequence immune response genes, has enabled a much better understanding, at least of the complexity of "autoimmunity" to be gleaned. This volume contains the chapters that summarize the plenary presentations given at The Impact of Biotechnology on AUTOIMMUNI1Y meeting in Florence, Italy in June 1993. They cover all aspects from pathogenesis to treatment. The association with infectious diseases and autoimmunity is comprehensively covered by David Isenberg who reviews major issues, such as the association of autoantibodies appearing after infectious disease and antibacterial antibodies associated with autoimmune disease.

Recent Developments in Graves' Ophthalmopathy offers an overview of the pathogenesis, assessment and management of patients with thyroid-associated eye disease. Each chapter is written by an expert and truly represents the current state of the art on the particular topic. This book can therefore almost be considered a textbook on this enigmatic disorder. Recent Developments in Graves' Ophthalmopathy is designed for all those interested in this disease, including basic scientists, clinical endocrinologists, ophthalmologists, radiotherapists, and orbital surgeons. The book gives a comprehensive overview of all aspects of Graves' ophthalmopathy. Subjects covered include the pathology of Graves' eye disease and the controversial views on its autoimmune pathogenesis; assessment of the eye changes using reliable measurements; medical management of Graves' eye disease with an overview of the many treatment options available to the clinician, including orbital radiotherapy and other immunosuppressive treatments; management of the thyroid disease; and finally, the techniques for performing various surgical procedures, which are explained and illustrated.

In transfusion medicine the scientific fundamentals of immunology have had a considerable clinical impact. Transfusion may suppress the immunity but some patients could suffer disadvantages including GvHD, alloimmunisation and possible cancer, where white cells (WBC) play pivotal roles in this phenomenon, presenting antigens and producing cytokines. A clinical application of this practice is LAK-cells targeted against cancer. MHC on the WBC may provide additional immunological modulations through series of secondary messengers. Thus reduction of WBC in the blood and bone marrow may be advantageous for patients. On the other hand, sharing a part of MHC or making the transplanted white cells anergic by storage may be even more advantageous for patients. CMV infection could mimic part of this MHC. UV radiation is effective in the inactivation of the WBC although filters are easy means for such removal. However, their accurate quantification requires flow cytometry that has considerable potential application in blood transfusions. Idiotypic antibody could play an important role in platelet theory. However, the potential infection risks in transfusion like HIV and HCV remain, but application of molecular biological methods like PCR or RT/PCR has great potentials in detection of infectious diseases, transplantation and genetic disorders. Immuno affinity purified concentrates, like factor IX and protein C, could reduce patients' immune functions, where in the future protein C could be derived from transgenic animals. Advances are sure to emerge through adoptive immunotherapy and gene therapies are exciting prospects when genes transferred into lymphocytes could be used to correct cell mediated immune deficiency, as in ADA.

Despite major efforts by the scientific community over the years, our understanding of the pathogenesis or the mechanisms of injury of multiple sclerosis is still limited. Consequently, the current strategies for treatment and management of patients are limited in their efficacy. The mechanisms of tissue protection and repair are probably even less understood. One reason for these limitations is the enormous complexity of the disease and every facet of its pathogenesis, the mechanisms of tissue injury, the diagnostic procedures and finally the efficacy of treatments and their side effects. The aim of this book is to review the most recent advances made in this highly complex field.

Fluorescence is a very powerful tool for work at the frontier of cell biology, photobiology and bioinstrumentation. The stated aim of the workshop was to highlight the significance of fluorescence work for the understanding of cell and tissue physiology, physiopathology and pharmacology, particulary in terms of the analytical use of fluorescent probes in oncology. In the organization of the workshop a multidisciplinary approach was selected. The purpose of the Advanced Research Workshop (ARW) was to bring together researchers in the various disciplines of tissue optics, imaging, microspectrofluorometry and state of the art probes, in order to explore the full benefits that can be derived in biomedicine through the convergence of these approaches. When applied to in vivo and in situ studies, fluorescence and related optical methods enable us to explore within tissues, cells and organelles photon effects previously understood only in solution photochemistry. Processes which can be studied at the molecular level by photophysics, photochemistry and physical chemistry can be evaluated in living tissue by fluorescence spectroscopy and imaging at the intracellular level in terms of structure and function. Thus, fluorescence adds a new dimension to cell biology and physiology. This approach is now supported by a full and versatile, rapidly growing armamentarium of new selective probes for organelles, enzymes, cations, cytoskeleton and metabolic control.

Osteoarthritis is the most common joint pathology which primarily affects the older population. The disease is characterized by unique pathological changes in some synovial joints, predominantly affecting the articular cartilage, but also entire joints, including the synovial tissue and subchondral bone. The remarkable growth of research on normal and abnormal biology of tissues in the articulating joint, including the application of novel molecular biological approaches and new imaging techniques, is reflected in this volume. It describes the current state of knowledge and helps to further understand the etiopathology of osteoarthritis, hopefully leading to early detection of the disease and novel treatment modalities. The volume contains contributions and discussions from a select group of investigators, all experts in this field, who met at the conference "The Many Faces of Osteoarthritis", held in June 2001 at Lake Tahoe, to acknowledge Klaus E. Kuettner and his contributions to osteoarthritis...

Organ Shortage: The Solutions is the latest subject in the Continuing Education series, organized by Fondation Marcel Merieux and Universite Claude Bernard in Lyon. The annual subject is chosen to reflect the status of the topical issues of the year, as taught by leading international experts. The contribution of transplantation and clinical immunology to advanced medicine is considerable and promising. The annual volumes in this series keep the reader abreast of these developments. "

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.

Connective tissue diseases demand study because of their frequency, morbidity and mortality. They present intriguing challenges in the fields of diagnosis, management and research. Their range has now expanded enormously so that no individual can master the whole subject, particularly as this relates to their immunological basis. Immunology of Connective Tissue Diseases has been written by experts who are either clinical or basic scientists. The book presents up-to-date reviews of the immunological basis of connective tissue diseases as it impacts on diagnosis, pathogenetic concepts, disease monitoring and management. The book is aimed at physicians interested in understanding the immunological basis of these diseases, and at immunologists who are either entering this field for the first time and would like to have a convenient state-of-the-art account of its status, or who are researching in one area and would like to acquaint themselves with the developments which have taken place in others.

Integrating Population Outcomes, Biological Mechanisms and Research Methods in the Study of Human Milk and Lactation is the product of the 10th Conference of the International Society for Research on Human Milk and Lactation, held on September 15-19, 2000, in Tucson, Arizona. The presented sessions at the meeting are as diverse as the volume itself. These sessions include the impact of micronutrient deficiencies during lactation on maternal and infant health, the premature infant, developmental immunology, breastfeeding in the industrialized world, and viral transmission in milk. Whenever possible, the sessions were organized to include human population research, research showing the biological underpinnings of the effects on human health, and important methodological issues. This volume is a contemporary and influential tool for human milk biologists, breastfeeding epidemiologists, biochemists, immunologists, clinical specialists, and all professionals and researchers in the field.

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

Hot Topics in Infection and Immunity in Children brings together leading experts in the field to provide a current and authoritative view concerning the hottest topics of concern to clinicians caring for children with infections and research scientists working in the areas of infectious disease, immunology, microbiology and public health. The book is based on a collection of manuscripts from a faculty of authors of international standing who contributed to a course in Paediatric Infection and Immunity in Oxford, UK in June 2003.

When we were first approached by the senior editors of this series to edit a book on interactions between the host and infectious agents, we accepted this offer as an exciting challenge. The only condition, readily agreed upon, was that such a book should focus on the immunology of infections in humans. Our reasons, if not biases, were severalfold. We sensed that the fields of microbiology and im munology, which had diverged as each was focusing on its individual search, were coming together. In agreement with the opinions expressed by Dr. Richard Krause in the Introduction, we strongly believed that the development of the immune system evolved in response to infectious agents and that the evolution of these agents was influenced in turn by the character of the host's responses. An inten sive examination of the multitude of primitive or more recently developed host defense mechanisms to determine their relative contribution to man's resistance to a given infectious agent appeared to us to be of crucial basic and practical interest. Many immune mechanisms studied in animals were being explored in humans and it appeared timely to focus particularly on what was known about man's resistance to infectious agents, correlating this information with lessons learned from relevant experiments in animal models.

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.

Antibody-directed enzyme prodrug therapy (ADEPT) directly addresses the major problem in cancer chemotherapy-its lack of selectivity. Antibody delivery combined with the amplification provided by the enzymatic activation of prodrugs enables selection to be made between tumour and normal tissue. ADEPT offers a novel field of opportunities in the therapy of systemic cancer and may be a major advance for the treatment of solid tumours. This book is the first to describe ADEPT in detail. Each chapter reviews an aspect of the immunology, enzymology, biochemistry, chemistry, and cancer chemotherapy which have been integrated into the ADEPT concept. An additional chapter describes the related approach of gene-directed enzyme prodrug therapy (GDEPT). This latter approach is still in its infancy but ADEPT has entered the clinic. The initial clinical studies with ADEPT are included and discussed in detail.

380 years ago, in the year 1614, Ubbo Emmius transplanted the gene ofscience from Ostfriesland into the education genome ofthe city ofGroningen as devel- oped by Regnerus Praedinius. He thereby founded the University ofGroningen. It is with great pleasure that the Faculty of Medicine as one of the founding faculties ofour University, welcomes you to this 19th International Symposium ofBloodTransfusion, whichwill coverthe themeofHereditaryDiseasesandtheir relation to Transfusion Medicine, where cell expansion, gene transfer and gene therapy are the read thread. Since the earlydays there has beena specificand sincere interest in inborn errors ofmetabolism and hereditarydisorders. This interest has resulted in a structured research, diagnostic and counselling facilities, and therapeuticapproaches where various disciplines within our faculty work closely together with groups from related faculties of the University of Groningen, as well as other national and international scientific institutions. The field of inborn errors, genetic abnormalities and mutations, and hereditary diseases covers a broad gamma of extremely interesting and exciting scientific aspects,whichrangefrom clearphysicalaberrationstomolecularanalysisofgenes and genomes, coding areas and amino acid sequences. It is intriguing to realise that the balance of life seemingly depends on the position or presence of one single molecule as a part ofthe total complex ofgenetic information in the cell.

Leading researchers review the activation of the mammalian immune system by bacterial DNA and its immunostimulatory sequences (ISS), and consider the applications of ISS in clinical medicine. The authors survey the latest findings concerning the receptor-recognition and signaling pathways triggered by ISS , the process of cell activation, and the potential vaccination strategies using ISS. Specific pharmaceutical applications discussed include infectious disease (Hepatitis B, HIV, and mycobacterial infections), allergy (asthma and conjunctivitis), cancer (lymphoma), and inflammation and autoimmunity (arthritis and colitis).

It is now 10 years since the first AIDS cases were reported in the USA. In that relatively short period of time, study of the disease has moved from the level of early clinical description to exhaustive and extensive laboratory characterization of the human immunodeficiency virus (HIV), the immune responses directed towards it and reasons for their failure. This volume provides contributions from clinical and basic scientists who are actively involved in research in a number of areas of current interest and controversy. Further progress in the clinical management of the HIV-infected patient will undoubtedly build on the basic knowledge about HIV and its modes of pathogenesis. The intimate relationship between HIV and the human immune system provides observations and questions that are relevant to viral immunopathogenesis in general. In the first chapter the clinical features of HIV immunodeficiency are re viewed, and aspects of its changing face are discussed. Dr Tersmette then presents evidence for changing viral characteristics at different stages of the disease. This view of close competition for ascendancy between HIV and the host immune response raises questions about current approaches to therapy."

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.