Our current understanding of a/~ T cell receptor (TCR) ex pressing T cells advanced from function and specificity to the molecular organization ofthe TCR.We now know that the TCR a and ~ chains together express specificity for (antigenic) peptides presented by the "responder" M H C allele, thus explain ing the phenomenon of MHC restriction at a molecular level. Surprisingly even though our perception of the molecular organization of the y5 TCR is well advanced, current knowledge of function and specificity of the y5 T cell subset is poor. There fore it appeared rather timely to bring together scientists pioneering research on y5 T cells forthe International Workshop on Function and Specificity ofy5 Tcells,held October11-14, 1990 at Schloss Elmau/Bavaria, FRG. Besides offering a scientific forum for open discussions, it was also hoped that such a workshop would be seminal for collaborative interactions and personal relationships among scientists "addicted" to y 15 T cells.

Recent progress in the fields of pharmacology and immunology has provided us with new possibilities for treating dermatological diseases. This book reviews the most important immunosuppressive and immunostimulatory drugs and gives helpful, practical information on the treatment of various dermatoses, including autoimmundiseases, atopic dermatitis, psoriasis, vasculitis, contact dermatitis, pyoderma gangrenosum, infectious diseases, and neoplasms of the skin - in particular, malignant melanoma.

those who deal with infectious diseases on a daily This two volume work stems from the belief of the Editors that infectious diseases are not only very basis. much with us today but, more importantly, that they There are several excellent textbooks dealing will continue to playa significant global role in mor with medical microbiology, and there are equally well-recognized books devoted to infectious dis bidity and mortality in all people. A continuing need for an informed and knowledgeable community of eases. The Editors of this work, on the other hand, laboratory scientists is fundamental. Data describing were persuaded that there was a need for a publica the global impact of infectious diseases are difficult tion that would bring together the most pertinent and to come by. Fortunately, a recent thoughtful and relevant information on the principles and practice of provocative publication by Bennett et al. (1987) pro the laboratory diagnosis of infectious diseases and vides us with data derived from several consultants include clinical relationships. While this two volume that clearly delineate the impact of infectious dis text is directed toward the role of the laboratory in eases on the United States today."

Although upstaged by the tragic appearance of the human immunodeficiency virus, herpes simplex viruses (HSV) types 1 and 2 continue to be major human pathogens against which we lack acceptable vaccines or other means of immunological control. The virus is large and complex, coding for 70 or more proteins. Although many mysteries remain to be unraveled, our knowledge base regarding genomic organization, gene expression and regulation, pathogenesis, and immune recog nition of component parts is quite considerable. Indeed, meet ings devoted entirely to herpesviruses are conspicuous by their frequency and excellent, yet sometimes exclusive, attendance. The purpose of this volume is to compile in a single book a series of reviews by leading investigators that deal with various aspects of virus-host interactions and which hopefully will pro vide clues as to how to best manage HSV from an immunobio logical perspective. Ultimately, one anticipates that a full under standing of virus-host interaction will lead to strategies useful for the prevention and control of HSV. The state of current progress with conventional vaccines is presented, as is a chapter on intracellular immunization. This latter novel approach to virus infections comes at approximately the bicentenary of Jenner's introduction of a successful conventional immunization strategy."

M. B. A. OLDSTONE Viruses are generally studied either because they cause significant human, animal or plant disease or for their utility as materials to probe a basic phenomenon in biology, chemistry, genetics or molecular biology. Arenaviruses are unusually interesting in that they occupy both of these categories. Arenaviruses cause severe human diseases known primarily as the hemor rhagic fevers occurring in South and Latin America (Bolivia: Machupo virus and Argentina: Junin virus) and in Africa (Lassa virus). Because such viruses produce profound disability and may kill the persons they infect, they are a source of economic hardship in the countries where they are prevalent. Further, they provide new problems for health care personnel owing to the narrowing of the world as visitors from many countries increasingly travel to and from these endemic areas. In addition, lymphocytic choriomeningitis virus (LCMV) can infect humans worldwide, although the illness is most often less disabling than those elicited by other arenaviruses. Yet LCMV is likely of greater concern to non-arena-virologists and experimentalists using tissue culture or animals, i. e. , workers in molecular biology, cancer research, virology, immunobiology, etc. , because normal appearing cultured cells or tissues and animals used for research may be persistently infected with LCMV without manifesting clinical disease or cytopathology and transmit that infection to laboratory workers (reviewed OWSTONE and PETERS 1978). For example, HINMAN et al.

The fourth workshop on Mechanisms in B-Ce11 Neoplasia was held in Bethesda. Maryland. at the National Institutes of Health on March 24. 25 and 26. 1986. The meeting was attended by approximately 150 participants and 58 presentations were given. The purpose of these workshops and the yearly publications has been to provide a means for exchanging the rapidly developing information in this field and to bring maJor problems into focus. Edited trans- cripts of the 1983 and 1985 workshops were published by Editiones Roche Bas1e, Switzerland. Papers brought to the 1984 workshop were published in Current Topics in Microbiology and Immunology, Vol. 113. Numerous retrovira1 recombinant viral constructs are now in general use in a variety of test systems, both in vivo and in vitro. These are proving to have interesting bio10gica1-prQperties. ------- Kecent1y developed systems for inducing B cell tumors are described: 1) The development of spontaneous ~-ce11 tumors in transgenic mice carrying deregulated mlGBP genes and the Ig heavy chain promoter; 2) a method for inducing *p1asmacytomas in BAL~/c mice with short latent periods of ca 70 days by infecting pristane treated mice with retroviruses carrying various types of deregulated mlGBP genes; 3) induction of pre-B cell tumors with erbB containing recombinant retroviruses; 4) induction of B-ce11 and other tumors by infection of neonates with recombinant retroviruses. Several retrovira1 constructs containing mlGBP sequences do not induce B-ce11 tumors in pristane conditioned mice *.

Vaccines have historically been considered to be the most cost-effective method for preventing communicable diseases. It was a vaccine hat enabled global eradication of the dreaded disease smallpox. Mass immunization of children forms the anchor of the strategy of the World Health Organization (WHO) to attain "health for all" status by the year 2000. Vaccinology is undergoing a dimensional change with the advances that have taken place in immunology and genetic engineering. Vaccines that confer short or inadequate immunity or that have side effects are being replaced by better vaccines. New vaccines are being developed for a variety of maladies. Monoclonal antibodies and T cell clones have been employed to delineate the immunodeterminants on microbes, an approach elegantly complemented by computer graphics and molecular imaging techniques. Possibilities have opened for obtaining hitherto scarce antigens of parasites by the DNA recombinant route. Better appreciation of the idiotypic network has aroused research on anti-idiotypic vaccines. Solid-phase synthesis of peptides is leading to an array of synthetic vaccines, an approach that is expected to attain its full potential once the sequences activating suppressor cells are discovered and the rules for presentation of antigens to T and B cells are better worked out. A new breed of vaccines is on the horizon that seeks to control fertility.

There is no doubt among experts that the prevalence of allergic diseases has increased in many industrialized countries in recent years. The rea sons for this increase are unknown; only suppositions exist. Many people focus on environmental influences. However, the assumption that air pollution alone is responsible for this increase seems to be too simple: many other influences, including the genetic predisposition of individual patients, allergen exposure, and possibly socioeconomic factors, also have to be taken into consideration. Although our understanding of the complex mechanisms of allergic diseases has considerably improved thanks to the progress made in ex perimental immunology and allergology, we still have a long way to go before this scientific knowledge is translated into new therapeutic mo dalities. For this reason, the scientific community welcomed the gathering of scientists from very different disciplines and different parts of the world at an international symposium, "New Trends in Allergy IV" together with "Environmental Allergy and Allergotoxicology III" in Hamburg in 1995. This volume contains the invited papers, covering a wide range from basic science to practical clinical diagnosis and therapy. A further unique feature of this event was the concomitant first official workshop of the Environmental Pollution and Allergy Committee of the International Association of Allergy and Clinical Immunology (IAACI), at which the state of scientific knowledge in this field was defined and formulated."

The rapid and continuous upsurge of interesting data in the subject of tumor immunology necessitates the publication of an annual series to furnish the updated materials to the students, researchers, and clinicians in this rapidly advancing field. Concepts and methodologies are ever changing. Also, current research in tumor immunology promises to offer breakthroughs in the future. Important is the need to communicate to the right people the exact role of immunodiagnostic methods and immunolog ical intervention in cancer prevention and treatment. The role of immuno therapy in combination with conventional modalities of treatment needs in its proper perspective. Oncogene, interferon, lympho to be understood kines, monoclonal antibodies, natural killer cells, platelet-mediated cyto toxicity of antibody-coated target cells, suppressor cells, platelet-derived factors, plasma-blocking factors, control of suppressor cell function, ab rogation of plasma-blocking factors, etc., are some of the areas that are continually advancing. Progress in these areas will have implication in cancer therapy. Further, it is already understood that if immunocompe tence of the host can be maintained at a reasonably good level, there exists the potential to increase the therapeutic indexes of conventional modalities of treatment. This series will attempt to present updated infor mation in all these areas based on contributed and solicited articles. P. K."

For more than ten years cell fusion techniques have been applied in studies on various lymphocyte functions. Ig expression was first studied in hybrids obtained by fusing myeloma cells with fibroblasts (1) or lymphomas (2), both of which do not produce Ig, and with Ig producing myelomas (3) or human blood lymphocytes (4). Kohler and Milstein (5) fused a myeloma with spleen cells from immunized mice. Up to 10% of the hybrids obtained secreted antibodies specific for the immunizing antigen. This suggested that plasma cells preferenti ally fused with the myeloma cells, a finding which was of enormous practical value. It was found that both Band T lymphocytes could be fused with the T cell tumor BW5147, which is however not permissive for Ig synthesis (6). A very large number of T cell hybridomas were generated by fusing BW5147 with cell populations containing in vivo or in vitro activated cells (7). The hybrids showed no specific T cell functions and binding assays for T cell receptors were not available. In particular, no hybrids were obtained which expreS1ed specific cytolytic activity that could be tested in short-term Cr release assays (8). However, the frustrations expressed about these failures, published in January, 1978 (9), were relieved by Taniguchi and Miller's publication a few months later of T cell hybridomas producing antigen-specific suppressor factors (10). Unfortunately, their hybrids rapidly lost factor production."

The skin allograft has been used as the test tool since the beginning of investiga tions of the fate of skin transplanted between two individuals of ordinary genetic diversity. This monograph is designed to furnish the transplantation work er with a review of the significant papers in which skin allografts and xeno grafts, applied to experimental animals and man, have played a role in acquiring a body of knowledge concerning the behavior and fate of these transplants and the reaction of the body to their presence. Skin, an essential organ for survival, a barrier between the "milieu inte rieur" of Claude Bernard and the "milieu exterieur," will remain the most frequently used transplant in transplantation research. Because it is highly antigenic, the final solution of the problem of acceptance of allografts of various tissues and organs will probably depend upon the achievement of a permanent survival of skin allografts. My personal interest in transplantation, which originated during my surgi cal training, was rekindled when I met Peter Medawar (today Sir Peter) in England during World War II. I had joined, in 1940, an American Volunteer Surgical Unit (The American Hospital in Britain), organized and headed by Dr."

During the past decade, there have been numerous direct and indirect scientific contributions to both the etiology and therapy of aplastic anemia and related bone marrow failure syndromes. Clinical observations, such as autologous bone marrow recovery after conditioning with immunosup pressive agents for bone marrow transplantation; failure to achieve en graftment in some identical twins without prior immunosuppressive ther apy; and hematologic response to immunosuppressive agents, have led to the concept of immune-mediated etiology of acquired aplastic anemia. Such a concept was further strengthened by laboratory findings, implicat ing the role of activated cytotoxic T lymphocytes and abnormal produc tion of inhibitory lymphokines. The immunologic mechanisms may also apply to the idiosyncratic bone marrow aplasias associated with drugs, toxic chemicals, and viruses. These agents may alter normal cellular recog nition sites by interacting with cellular components and result in loss of self tolerance. Immunologic mechanisms have long been advocated in many other organ failures, and the hemopoietic organ is no exception. It is of interest that parallel clinical and laboratory investigations in juvenile diabetes mellitus type I and in rodent models of this disease have yielded results compatible with the same pathogenic mechanisms. The infiltration of pancreatic islets by activated T lymphocytes, functional and morphological alterations of islet cells upon incubation with lymphokines such as gamma interferon and tumor necrosis factor, and clinical response to cyclosporine are a few examples."

Fibronectins comprise a class of high molecular weight glycoproteins present both in extracellular matrices and in soluble form in body fluids. Although they have been studied for about forty years, their real significance emerged only during the past decade. Intensive research has focused on their role in platelet function, cell migration, the cytoskeleton, reticuloendothelial function, and on alterations in fibronectin distribution during development and disease. Fibronectins have emerged as glycoproteins with a very interesting set of properties generally involving adhesion of cells to cells or to extracellular material. In more recent years, the complete sequences of several fibronectin molecules and their genes were determined, the relation between structure and function was understood and much has been learned about cell surface receptors for fibronectins and other adhesive ligands. Having been at the forefront of all these exciting developments, the author has synthesized the entire field and with all the latest information at hand for the first time given it a clear perspective.

It has been a challenge for us to edit this volume of Endocrinology and Metabo lism: Progress in Research and Clinical Practice. The topic of the pathogenesis of insulin-dependent, type I diabetes mellitus is particularly appropriate for this series, since advances in this area have been made, to a large extent, by applying state-of-the-art laboratory techniques to clinical samples. Over the last several years, a number of lines of evidence have been gathered, suggesting that classic type I diabetes mellitus results from the autoimmune des truction of pancreatic beta-cells in genetically susceptible individuals. This hypothesis is particularly appealing because it offers a rational approach to the prevention of diabetes by immunosuppression. We have tried to present a balanced, authoritative summary of the information currently available to support the autoimmune hypothesis for the pathogenesis of human type I diabetes, to place this information in historical perspective, to include relevant information from animal models of type I diabetes in which more invasive experimentation is ethical, and, finally, to update the reader on the current status of attempts to intervene in the progression of diabetes with immunosuppressive drugs. New York, New York Fredda Ginsberg-Fellner Robert C. McEvoy Contents Preface.. . . .. .. .. . . . . . . . . . . . . ... . . . . . . . . . . . .. . . . . . . .. . . . . v Contributors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Xl . . . . . . . . . . . . . 1. The Autoimmune Hypothesis of Insulin-Dependent Diabetes: 1965 to the Present . . . . . . . . . . . . ..................... . . . . . .

This volume documents our growing understanding of the human major histocompatibility complex. The application of this information is ever more important as the limits of transplantation continue to be reduced, including the recent success of bone marrow transplantation between unrelated but closely matched individuals. In addition, the need to transfuse platelets in the face of immunologic barriers continues to challenge transfusion services. Thus, the serologic information summarized in this volume is essential for optimal patient care. At the same time, recombinant DNA technology has led to a revolution in our understanding of many aspects of basic biology. Among the advances has been the initial characterization of the structure of some HLA loci. While this will ultimately improve clinical services, constant reference to serologic data is essential so that the powerful new techniques can be applied in the most effective ways. The timing of the First Red Cross International Histocompatibility Workshop is fortunate as it brings together experts from around the world to address the state of the art. We are all grateful to Dr. John Lee and his colleagues for organizing the workshop, and for bringing together in this volume the material to be presented in Beijing during October 17-23, 1990. Leon W. Hoyer, M.D.

Vaccines have historically been considered to be the most cost-effective method for preventing communicable diseases. It was a vaccine that en abled global eradication of the dreaded disease smallpo. ."

The human leukocyte antigen (HLA) or tissue types are the products of a rapidly developing field of knowledge within the last 20 years. In the early stages of the research many investigators suspected the existence of a complex series of transplantation antigens, but it was widely believed that these antigens would not be well-defined even in this century. Yet in the last two decades as many as 124 different HLA antigens determined by at least 7 very closely linked genes located on the short arm of chromosome 6 have been identified and subsequently agreed upon by an international nomenclature committee. 1 Extensive international collaboration fueled by the potential clinical application of these antigens to clinical transplantation has advanced the field rapidly. There were nine inter national histocompatibility workshops held during this period. Although iden tification of HLA antigens was of primary clinical importance in transplantation 2 and of great basic interest in human genetics and anthropology, a rather un expected bonus has been the determination that HLA antigens are associated with disease susceptibility to a greater extent than any other known genetic marker in man. In the past, many genetic polymorphisms have been suspected to be associated with diseases. The most extensively studied markers are blood groups, enzymes, and serum proteins. A comprehensive account of published studies, totalling approximately 1,000, of these markers is available in a book by Mourant et al."

Through numerous discussions with colleagues it became apparent that the time was right to begin a series of workshop-like meetings on myeloid tumorigenesis. Myeloid tumors are the nonlymphocytic tumors of the hematopoietic system which include tumors of the neutrophilic, monocytic, erythrocytic, basophilic (mast cell) and megakaryocytic lineages. Pioneering studies in myeloid tumorigenesis were initially made in chickens with the discovery of retroviruses that induce various kinds of myeloid tumors acutely (myelocytomatosis, myeloblastosis, and erythroblastosis). These avian retroviruses were subsequently shown to contain the oncogenes v-myb, v-~, v-~, v-erbA, or v-erbB. There have been dramatic advances in studying the pathogenesis of hematopoietic tumors in genetically defined mammalian systems. Many of the well developed model systems in inbred mice, have focused on T- and B-1ymphoma development. Although myeloid tumors have been found in mice, they have not been studied as intensively as lymphoid tumors. Possibly this is because myeloid tumors are less common than lymphoid tumors. Recently, there has been renewed interest in murine myeloid tumor systems. This focus has resulted from 1) the discovery of inbred strains of mice (e. g. BXH-2, AKXD- 23, SJL/J) that are highly susceptible to spontaneous or induced myeloid tumorigenesis; 2) establishment of transplantable murine myeloid tumors (e.

Any professional concerned with immunology will be interested in this book dedicated to the memory of Milan Hasek, former director of the Prague Institute of Experimental Biology and Genetics. Prof. Hasek was a congenial scientist and most amiable person - a personal friend of almost all leading immunologists around the world. He was displaced from his post of director in 1970, yet had a lasting impact upon his students and the group known as the Prague School of Immunogenetics. The topics covered in the contributions range from tolerance, immune network, and immunogenetics to the immunology of bacterial and viral infections. They are written by 27 of Prof. Hasek's former co-workers who emigrated to western countries around or after 1968 and became well-known and distinguished scientists in the field. The papers include their personal reflections of the Prague Institute, their impressions upon arriving abroad and their interesting experimental work since then. The book also provides a complete bibliography of their publications after leaving Czechoslovakia.

Diabetes mellitus represents one of the most frequent and serious clinical syn dromes in contemporary medicine. Since the end of the nineteenth century, the endocrine pancreas has been implicated in the pathogenesis of this disease. Several pathologists of the twentieth century detected various lesions and mor phologic alterations in the pancreatic islets of diabetic patients, but the patho physiologic basis of their findings remained long obscure. The systematic mi croscopic work of WILLY GEPTS clarified the views and related the variety in histopathology to differences in origin, duration and clinical expression of the disease. Over the past two decades, the concept of a multifactorial origin of diabetes has become widely accepted. Various agents and mechanisms have been identified which can lead to a quantitative or qualitative deficit in pancre atic B-cells. The purpose of this book is to bring an update on the many path ways which may induce an absolute or relative insufficiency in insulin release and hence a diabetic state. Rather than bringing a complete account on all re search relevant to the understanding of the pathology of the diabetic pancreas, the authors of the various chapters of this volume have focussed on selected processes which can impair B-cell function, survival or regeneration.

When I entered the field of allergy in the early 1970s, the standard textbook was a few hundred pages, and the specialty was so compact that texts were often authored entirely by a single individual and were never larger than one volume. Compare this with Allergy Frontiers: Epigenetics, Allergens, and Risk Factors, the present s- volume text with well over 150 contributors from throughout the world. This book captures the explosive growth of our specialty since the single-author textbooks referred to above. The unprecedented format of this work lies in its meticulous attention to detail yet comprehensive scope. For example, great detail is seen in manuscripts dealing with topics such as "Exosomes, naturally occurring minimal antigen presenting units" and "Neuropeptide S receptor 1 (NPSR1), an asthma susceptibility gene." The scope is exemplified by the unique approach to disease entities normally dealt with in a single chapter in most texts. For example, anaphylaxis, a topic usually confined to one chapter in most textbooks, is given five chapters in Allergy Frontiers. This approach allows the text to employ multiple contributors for a single topic, giving the reader the advantage of being introduced to more than one vi- point regarding a single disease.

Due to the topology and structure of the lymph nodes, their role in the pathogenesis and development of diseases is a very special one. Each organ and even each organ-related region of the body has its own group of lymph nodes, specific topological reactions, such as in circumscribed inflammation or in the metastatic spread of malignant tumors. On the other hand, all the lymph nodes of an organism join in a uniform function effected by highly differentiated structures. Volume 84 of Current Topics in Pathology presents our current knowledge about the structure and reaction patterns of this "sec ondary" lymphoid organ. Despite our original intention to publish all the contributions in one book, it became necessary to divide them: Part 1 focuses on the involved nodal compartments, cell types, and functions, while Part 2 describes their reactions in inflammatory, neo plastic, and immune-deficient diseases. Even with the cooperation of more than 30 authors, the coverage cannot be exhaustive. The scope of both parts is limited to those reactions that can be described by direct and indirect morphological methods, including modern tech niques such as immune electron microscopy."

"Immunopharmacology" , why not "pharmacoimmunology"? Professor H. O. Schild University College London, 1962 An intact immune response is essential for survival, as is evidenced by the various innate immune deficiency syndromes and by the emergence of the acquired immune deficiency syndrome (AIDS) as a pandemic during the last decade. Substances which stimulate the immune response might contribute to the therapy of AIDS and its precursor, AIDS-related syndrome, as well as of other clinical conditions in which immune responses can be diminished, such as carcinoma and infections. In other circumstances, an intact or heightened immune response may pose clinical problems; hence there is need to suppress, or diminish, components of the immune response. For instance, it is necessary to impair cellular immunity in order to ensure lasting acceptance of heterografts and it is already established that agents effective in transplantation are therapeutically effective in an range of autoimmune diseases. More recently, experimental studies have indicated that aberrant manifestations of humoral immunity, as in allergies, may also be amenable to pharmacological intervention.

The papers in this book were presented at the 6th Workshop on Mechanisms in B-Cell Neoplasia, held in Bethesda, March 23-25, 1988. On alternate years this meeting is sponsored by the . ;. Basel Institute of Immunology in Basel, Switzerland and by the National Cancer Institute in Bethesda, and is attended by 100 to 150 parti cipants. This 6th workshop, like the preceding five, was characterized by intense and enthusiastic discussion which reflects, we think, the exciting growth and development of this field. It is quite clear, however, that despite many general advances an understanding of the precise underlying mechanisms in B-cell tumor development is not yet defined. Probably, there is no single mechanism for all the various forms of B-cell neo plastic development. Many different forms of B-cell neoplasms are known, and these are distinguished by several characteristics: 1) the stage of development attained by the tumor stem cells; 2) mode of growth (slow or fast); 3) association with natural or inductive etiologic agents and 4) specific and consistent mutational mechanisms such as retroviral insertion, chromosomal rearrangement. Those charac teristic forms which arise naturally in relatively high frequency or those tumors with hallmark properties which can be induced consistently are the models most frequently studied, e. g. , endemic Burkitt's lymphoma, follicular lymphoma, acute and chronic lymphocytic leukemia and mUltiple myeloma in man; bursal lymphoma in chickens; Abelson virus induced pre B cell lymphomas and plasmacytomas in mice and immunocytomas in rats. Each model system, has special problems and advantages.

There is now widespread recognition that emotional problems, to say nothing of the interactions of emotions with other manifestations of illness and disease, constitute a substantial component of all human suffering. For too long the pro vision of medical care has been restricted to the physical aspects of that suffer ing while the psychological aspects have been shunned. Whether through igno rance about the nature of emotional illness and its clinical management, or through uncertainty about the legitimacy of their ministrations, physicians and many other health professionals have left the care of psychiatric problems to psychiatrists and other mental health professionals. For a variety of reasons this strategy is no longer feasible and substantial changes are required. The extent of the needs, the nature of the presenting problems, the ex pectations of the patients, the prohibitive costs of alternative approaches, and the lack of trained mental health professionals make it imperative that general health workers learn to cope with the psychological and behavioral health prob lems of their patients. There are no other alternatives if the realities of comtem porary suffering, limited resources and psychobiological knowledge are accepted. It is to the pragmatic knowledge base for this essential component of contemporary health care that this book makes a seminal contribution. Dr."