This volume contains the contributions to the workshop "The Semiotics of Cellular Communication in The Immune System" which took place at "11 Ciocco" in the hills north of Lucca, Italy, September ~-12, 1986. The workshop was the first meeting of what we hope will be a broad consideration of communication among lymphocytes, and focused on the new interdisciplinary branch of biological sciences, immunosemiotics. It is in the realm of the possible, if not the probable, that in the future a number of scientists larger than the thirty present at 11 Ciocco will find immunosemiotics to fill a need in scientific thinking and a gap between biology and the humanities. This might lead to growth and flourishing of the branch, and in this case the first conference and this first book could be blessed by the impalpable qual ity of becoming "historical", if in an admittedly 1 imited sense. Just in case this should happen the organizers/editors think it wise to set the record straight at this particular time, about the sequen~e of events and circumstances that crystallized the archeology of the "11 Liocco" gathering. They feel a sort of obligation to this endeavor: it has happened all too often that innocent historians have been left in utter confusion by the careless founders of new religions, schisms, revolutions, et cetera, who simply forget to jot down the facts before the whirlwind of time engulfs them in its fog.

Current Topics in Medical Mycology, which is a new annual series published by Springer-Verlag, is intended to summarize current topics in medical mycology for medical mycologists and other scientists who are work- ing in microbiology and immunology. Topics to be in- cluded in each year's volume will serve as contemporary reviews, summaries of current advancements and future directions, and mechanisms to enhance the interdiscipli- nary use of medically important fungi in the areas of pathogenesis, epidemiology, mycotoxins, taxonomy, and other areas where basic, applied, and clinical science are used. Michael R. McGinnis Contents ix Contributors 1 Pathology of the Mycoses in Patients with the Acquired Immunodeficiency Syndrome (AIDS) FRANCIS W. CHANDLER 1 Composition and Structure of Yeast Cell 2 Walls 24 GRAHAM H. FLEET 3 Animal Models for Candidiasis M. NEAL GUENTZEL, GARRY T. COLE, and 57 LEODOCIA M. POPE 4 Dermatophyte Antigens and Cell-Mediated Immunity in Dermatophytosis 117 TAAVIKAAMAN 5 Natural Cell-Mediated Resistance Against Cryptococcus neoformans: A Possible Role for Natural Killer (NK) Cells J UNEANN W. M URPHY 135 6 Biotyping of Medically Important Fungi FRANK C. ODDS 155 7 Characterization of Protein and Mannan Polysaccharide Antigens of Yeasts, Moulds, and Actinomycetes ERROL REISS, MILTON HUPPERT, and ROBERT CHERNIAK 172 Contents viii The Changing Epidemiology and Emerging 8 Patterns of Dermatophyte Species 208 JOHN WILLARD RIPPON 9 Paracoccidioides brasiliensis: Cell Wall Glucans, Pathogenicity, and Dimorphism GIOCONDA SAN-BLAS 235 10 The Role of Zinc in Candida Dimorphism 258 DAvID R. SOLL 11 Killer Yeasts REED B.

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 immunological intervention in cancer preven tion and treatment. The role of immunotherapy in combination with conven tional modalities of treatment needs to be understood in its proper perspective. Oncogene, interferon, lymphokines, monoclonal antibodies, natural killer cells, platelet-mediated cytotoxicity of antibody-coated target cells, suppressor cells, platelet-derived factors, plasma-blocking factors, control of suppressor cell func tion, abrogation of plasma-blocking factors, and so forth, 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 immunocompetence 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 information in all these areas based on con tributed and solicited articles."

The present monograph will concern itself with those disorders of the endocrine system, either associated with destruction, interference with function or hyper- function, which are considered to be due to auto-immune processes. Endocrinopathies Non-endocrine auto-immune disorders associated with the endocrinopathies Graves' (Basedow's, Parry's) disease Pernicious anaemia Hashimoto's thyroiditis Vitiligo Idiopathic Addison's disease Myaesthenia gravis Insulinopenic diabetes mellitus Sjogren's syndrome Auto-immune oophoritis and orchitis Rheumatoid arthritis Auto-immune hypoparathyroidism Idiopathic thrombocytopenic purpura Auto-immune hypophysitis Chronic active hepatitis Possibly some cases of infertility Primary biliary cirrhosis due to anti-sperm antibodies Reproduced with permission from Volpe (1977) The above table indicates those organ-specific endocrinopathies considered to be due to auto-immune factors, as well as those non-endocrine, organ-specific auto-immune disorders which may be associated with them (Volpe 1977). It is evident that such disorders, occurring without any obvious external cause, raise the very elementary question of how immune processes directed against self- constituents could be initiated. Generally, of course, the immune system acts as a regulatory and defence mechanism, and disorders of auto-immunity represent breakdowns in this regulatory system. The following chapters will be concerned with the individual components ofthe endocrine system so affected by auto-immune processes; it will first be necessary to provide an initial chapter for the purpose of summarizing some general principles of immunology, in order to place the immune disorders of the endocrine system in context.

Allergic Contact Dermatitis presents all up-to-date chemical and physio-chemical concepts for the study and understanding of allergic contact dermatitis (ACD). The book covers all aspects of ACD - skin penetration and metabolism, identification of sensitizers and hapten-protein interaction, including new concepts of increasing importance such as molecular recognition and quantitative structure-activity relationships. In addition, comprehensive references are provided, making this the most complete available text-book for dermatologists.
Allergic Contact Dermatitis reaches an equilibrium between fundamental concepts and clinical applications and thus presents an essential guideline to dermatologists, allergologists, biochemists and toxicologists.

The prevention and control of infectious diseases represents, even today, an important public health problem for responsible national and international authorities. Newly emerging p.athogens such as human immunodeficiency virus (HIV), legionella, and bovine spongiform encephalopathy (BSE) have captured current public awareness. Despite significant success against smallpox, polio myelitis, mumps, and measles, the vast majority of infectious diseases are yet to be satisfactorily controlled. Limited efficacy of some vaccines, e. g., against influenza viruses, or their nonavailability have hampered an effective control of many infections. A meaningful reduction of the health risks posed by microbial pathogens is of crucial importance. Increased efforts need to be exerted in areas of active and passive immunization as well as in stimulation of enhanced nonspecific resistance .. Progress in the field of infectious diseases can be accelerated when a generation of new improved vaccines are developed. These vaccines should be capable of activat ing the cellular and the humoral immune responses as well as inducing persistent immunological memory. Development of novel regimens for enhancing natural resistance against infections is also progressively gaining in importance. The urgency increases as chemotherapy against viral and other infections further continues to be plagued by a carousel of a limited number of licensed drugs, problems of side effects, and development of drug resistance. It is becoming expedient that future strategies embrace a policy directed towards triggering mechanisms capable of inducing specific and nonspecific host defences."

Aromas are an integral part of our civilised society. They are not only used in fine perfumes, but also in numerous other articles with which we have daily contact. Another new development has been the agricultural use of aromas as a "biological weapon" to combat insects and other pests. In the field of dermatology, aromas are today among the most frequent sensitizers and may trigger allergic contact eczemas. This volume presents numerous aspects of the topic for the first time in comprehensive form. In an introduction, the chemistry of frequently used aroma components is described, together with the art of perfume composition that has been refined over the centuries. In a chapter on neuropharmacology, the mechanisms of scent recognition are described in detail.

For a long time, immunology has been dominated by the idea of a simple linear cause-effect relationship between the exposure to an antigen and the production of specific antibodies against that antigen. Clonal selection was the name of the theory based on this idea and it has provided the main concepts to account for the known features of the immune response. More recently, immunologists have discovered a wealth of new facts, in the form of different regulatory cells (helpers, suppressors, antigen presenting cells), genetic determinations of immune responses such as those involved in graft re jections, different molecular structures responsible for intercellular interactions such as interleukins, cytokins, idiotype-antiidiotype recognition and others. While furthering our understanding of the local interactions (molecular and cellular) in volved in the immune response, these discoveries have led to a questioning of the simplicities of the classical clonal selection theory. It is clear today that every single immune response is a cooperative phenomenon involving several different molecular and cellular interactions taking place in a coupled manner. In addition, cross reactivity to different antigens has shown that responses of the whole im mune system to different antigens are not completely isolated from one another and that the history of encounters with different antigens plays a crucial role in the maturation of the whole system. Thus, problems of complexity, generation of di versity and self-organization have entered the field of immunology.

Many of the fundamental concepts of animal virology originated from the study of the variola-cowpox-vaccinia virus system with vaccinia virus serving as the type species (Fen- nerand Burnet 1957; Burnet 1959; Fenner 1976a, b). The importance of the Poxviridae(Fen- ner 1979) for the study of viruses as biologic entities and in defIning the events which occur in virus-infected cells are exemplifIed by investigations which: (a) described the epidemiology of a virus disease in an animal population (Fenner1949, 1959b); (b) em- ployed electron microscopy to study virion structure (Peters 1956, Nagington and Home 1962, Dales and Siminovitch 1961) and to derme the morphologic stages of virion develop- ment in infected cells (Morgan et al. 1954, Dales 1963); (c) dermed and elaborated on the mechanism of nongenetic reactivation for an animal virus (Joklik et al. 1960a, Fenner and Woodroofe 1960, Hanafusa 1960); (d) described the intracellular uncoating of a viral genome (Joklik 1964a, b); (e) studied the antigenic structure and complexity of poxvirions (Loh and Riggs 1961, Woodroofe and Fenner 1962, Appleyard et al. 1964, Appleyard and Westwood 1964); (1) described the use of chemotherapy to treat viral infec- tions (Bauer et al. 1963); (g) fIrst demonstrated the presence of virion-coded enzymes encapsulated within virions (Kates and McAuslan 1967, Munyon et al. 1967); and (h) established the H -2 restriction of cytotoxic T-cell killing of virus-infected cells in the murine system (Doherty et al. 1976).

African and South American trypanosomiases are notable features of clinical and veterinary practice in their respective endemic areas and, as such, are of considerable economic importance. Scientifically, however, their importance ex tends beyond their clinical significance, as the trypano somes are intriguing and easily manipulated models for the study of the control of gene expression, membrane chemistry, proliferation and differentiation. It is clear from the scientific press that the rate of advance has "hotted" up in these areas of trypanosome research over the past 5 years and so a single-topic volume within the scope of the present series seemed timely. As ever, the final admix ture of review topics was a compromise between what was appropriate and what was available - fortunately with the former in vast excess. I should like to highlight two omissions, made for en tirely different reasons. The first is a detailed treatment of the molecular biology of the variant surface glycopro teins of the African trypanosomes (in particular Trypano soma brucei and T. equiperdum). This topic has been the subject of several reviews, for example, BORST and CROSS (1982)1 and TURNER (1982)2, and so was excluded from the present volume. The second omission is a review of the first-class work on genetic recombination from the group of Dr. Leo Jenni at the Schweizerisches Tropeninsti tut, Basel. This group has used isoenzyme markers to show that T."

Leading researchers present contemporary treatment of in situ hybridization applied to current issues in animal virus pathogenesis. The most recent methods are given for locating viral genes in whole animal section and for defining the number and type of cells surrounded by viruses. The genetic programs played out in these cells and the newer methods of hybridization at the electron microscopic level provide valuable insight into the complexities of virus-host interaction.

The development of innovative molecular techniques such as pulse-field gel electro phoresis, cDNA subtraction libraries and chromosome hopping libraries coupled with the increasing popularity in the prospect of sequencing mammalian genomes, has triggered a resurgence of interest in finding and characterizing genes that playa role in modifying immune processes and diseases. Genetically defined strains of mice (e. g., inbred strains and recently derived stocks of wild mice) provide ideal models for examining the genetic control of diseases as a result of their syntenic relationship with man in genetic composition as well as linkage conserva tion. Due to the relative ease of producing a specific genotype via appropriate breeding schedules, murine models may provide the only hope for unravelling those complex disease processes under mUltigenic control. This issue of CTMI is a collection of papers on the characterization and mapping of genes involved in mutations and dysregulated immune responses which produce disease phenotypes. These papers were presented at a workshop which was devoted to examining reverse genetic approaches at localizing, cloning and characterizing genes involved in a variety of developmental, autoimmune, neoplastic and infectious disease processes. In the first of three sections, a series of papers outline the most currently used methods of mapping and isolating genes whose products are unknown. The papers, following, are devoted to specific gene systems whose dysregulation is likely to produce mutant or disease phenotypes."

Oral tolerance is a major immunological property of the gastrointestinal mucosa. It plays a critical role in immune defence by preventing inflammatory and allergic responses to dietary and non pathogenic microbial antigens. The interest in oral tolerance has been renewed in the recent years, due to novel insights on its cellular mechanisms and potential clinical applications in the treatment of autoimmune diseases. Oral Tolerance: Cellular and Molecular Basis, Clinical Aspects, and Therapeutic Potential, has been designed as a concise yet comprehensive overview of the newest fundamental and clinical advances in the field. Based on the outstanding contribution of world experts, this book will be helpful to students, clinicians, and researchers working in mucosal immunology and gastroenterology. The first part of this volume describes the structure and functions of the gastrointestinal mucosa and the fundamental features and mechanisms of oral tolerance, including the role of T cells, cytokines, IgA antibodies, and bacterial antigens. The second part explores the clinical implications of the disruption of oral tolerance in Inflammatory Bowel Diseases, food and milk allergies, and coeliac disease in particular. The final chapter focuses on the clinical potential of oral tolerance as a promising therapeutic tool.

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 u- ally 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.

The data summarized in this chapter show that morphological transformation and oncogenesis by adenoviruses are brought about by the coordinated activity of regions E1A and E1B. Gene products of each of these subregions appear to fulfill distinct roles in oncogenic transformation, with the possible exception of the product(s) encoded by the O. 9-kb E1A mRNA. Also unclear is the func- tion of the 20-kd E1B protein, which has a small role, if any, in morphological transformation, but appears to be essential for the development of the oncogenic phenotype, as defined by the ability of transformed cells to grow in immuno- deficient nude mice. The differences in biological properties of oncogenic and nononcogenic adenoviruses must be attributed to differences in the primary structure of the respective E1A and E1B gene products, in particular of the product(s) of the 1. 0-kb E1A mRNA and of the 55-kd protein encoded by the 2. 2-kb EiB mRNA. The availability of cold-sensitive adenovirus mutants has enabled us to conclude that the transformed phenotype is maintained as a result of continuous expression of at least region E1A gene products, and is therefore not the result of a hit-and-run mechanism. Despite the progress in our understanding of adenovirus transformation and oncogenesis, virtually nothing is known about the precise mechanism by which the viral gene products bring about the neoplastic changes in cells. The only exception is the demonstration that Ad12 region E1A (1.

Allergy is one of the major health problems of most modern societies. Although allergic diseases are well-known for almost two hundred years, their prevalence has increased dramatically over the last decades. Allergic reactions manifest in various organs, most commonly in the skin and mucous membranes, the frontier surfaces where the contact between the individual and the environment takes place. In a very concise and practical way this book covers all aspects of allergic reactions from pathophysiology to diagnosis, therapy and prevention with a strong focus on relevant aspects for the everyday work of the practising dermatologist and allergist in the hospital or office. This book reflects the rich personal experience of a German allergist with international training and reputation, who is active in immunology and allergy research and practice for almost 30 years. In this book, not only IgE-mediated allergic reactions are covered but all other kinds of allergies such as atopic eczema, contact dermatitis, drug eruptions, anaphylaxis and food allergies are equally represented as well as psychosomatic aspects and problems of environmental intolerances.

This key work in the field draws on a broad spectrum of molecular biologic, biochemical, and immunogenetic approaches in combination with human and murine in vitro cell culture and in vivo model systems to address questions in mucosal immunity. Humans produce more immunoglobulin A (IgA) than all other antibody isotypes combined. This book is designed to serve as a concise reference of the present knowledge of the biology of IgA.

This volume forms part of a prestigious series and covers the latest advances in our understanding of the pathophysiology and treatment of asthma. Our understanding of asthma has changed dramatically in recent years, and much of this new information is brought together in this volume written by inter nationally recognised authorities. The aim of the book is to review in depth the changing concepts of inflammatory processes in asthma and to discuss the implications for research of this common chronic disease. Many of the advances in and future therapy our understanding of asthma have originated from a pharmacological approach, and this volume highlights the promising new options for pharma cological intervention. It is hoped this book will be invaluable for research scientists and clinic ians involved in asthma research and will be a major reference resource for chest physicians and those involved in the development of novel pharmaceu tical entities. Each chapter is extensively referenced, generously illustrated with clear diagrams and photographs, and represents a state-of-the-art review of this growing area. c.P. PAGE P.l. BARNES Contents CHAPTER 1 The Pathology of Asthma: An Overview L.A. LAmNEN and A. LAmNEN. With 10 Figures ...................... 1 A. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . 1 . . . . . . . . . . . . . . . B. Methods to Investigate the Pathology of Human Asthma ............ 1 C. Bronchial Epithelium and Inflammatory Cells in Asthmatic Patients Between Attacks ........................... 2 I. Mast Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . 4 . . . . . . . . . . . . . . II. Eosinophils ............................................... 7 III. Neutrophils.............................................. 10 D. Bronchial Epithelial Inflammation During an Asthma Attack. . . . . .. . 10 E. Epithelial Regeneration .... . . . . . . . . . . . . . . . . . . . . . . .. . . 12 . . . . . . . . ."

This book is a collection of critical reviews about a diverse group of virus families with two features in common: the stable repository of genetic information in each virus is RNA, and each virus modifies and appropriates a particular patch of the eukaryotic cell membrane system to complete its structure. The reviews take the reader from the level of virus genome structure and expression through the quaternary interactions between virus-specified elements and cellular components that cooperate to produce virus particles. There are spectacular illustrations in this volume, but it is much more than a picture gallery. Reading widely in this book can be an effective antidote to overspecialization: in these pages, you are likely to learn much about viruses and about cells that you didn't know before; you'll discover illuminating parallels between diverse virus families; you'll come away with a sharpened awareness of important things that are still to be learned. Memphis, Tenn. , Summer 1984 David W. Kingsbury Preface This book was written at the suggestion of Dr. David W. Kingsbury made at a work shop on viruses organized by the Multiple Sclerosis Society in Aspen, Colorado, U. S. A. , three years ago. Originally, we had thought to focus on the morphological aspects of viral assembly. Later, during our discussions on the process of budding of enveloped RNA viruses, it became evident that we should include biochemical data in our review and correlate them with the structural aspects of virus maturation.

Postreplicative methylation of bacterial DNA has long been known to be the molecular basis of" modification," which protects DNA against destruction by restriction endonucleases. More recently, another function of DNA methylation was found in Escherichia coli, where methy- lation is involved during DNA replication in the recogni- tion of old and newly synthesized strands. The intensive search for new restriction enzymes during the 1970s yielded an enormous arsenal of such enzymes and re- vealed the ubiquitous distribution of restriction/modifi- cation systems in the bacterial kingdom without provid- ing much information on the corresponding modifica- tion methyltransferases. However, it is obvious that DNA methyltransferases represent an ideal class of en- zymes to those interested in protein/DNA interactions; these enzymes are at least as interesting as the restriction enzymes, with which they share the capacity to recognize and interact with specific sequences of DNA. In recent years the interest in DNA methylation has been greatly stimulated by two discoveries: the correla- tion between gene expression and hypomethylation in eukaryotes and the convertability of DNA into its Z form through cytosine methylation. In fact, studies on DNA methylation are now being intensively performed in many laboratories. A description of the state of the art of DNA methylation has been the topic of two con- gresses: The Cologne Spring Meeting in 1981 organized by WALTER DOERFLER and an EMBO Workshop at Nethybridge in 1982 organized by ROGER ADAMS.

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.

Contents: Introduction and Overview Lymphopoietic Growth Factors: Pathophysiology of T-Cell Mediated Shock Induced by Bacterial Superantigens - Natural Killer Cells and Interleukin-2-Activated Killer Cells - TumourImmunogenicity Induced by Exogenous Interleukins - Cytokine Gene Therapy of Cancer - Analysis of T-Cell Receptor Variability in Tumour Infiltrating Lymphocytes - Clinical Studies with Interleukin-2: An Overview - Clinical Trials with Local Administration of Lymphopoietic Growth Factors - Clinical Trials with Interlaukin-2. The Rome Experience. Haematopoietic Growth Factors: Lymphohaematopoietic Growth Factor Use in Lung Cancer Patients - Clinical Trials with Haematopoietic Growth Factors and Peripheral Blood Stem Cells

Many bacteria, such as certain Neisseria and Haemophilus or Escherichia coli, are able to withstand the bactericidal activity of complement and phagocytes. This bacterial self protection is brought about by encapsulation. Bacterial capsules thus enable the pathogenic bacteria to survive in the host by counter action or evasion of the nonspecific host defense in the early pre immune phase of an infection. It is only in the late immune phase of the infection, when specific anticapsular antibodies are formed and enforce the host's defense system, that this protective action is overcome. Encapsulated bacteria are then killed and eliminated. Interestingly, some capsules can not or only inefficiently be handled by the immune system. The ensuing lack of antibody formation results in a prolonged susceptibility of the host to the pathogenic bacteria exhibiting such capsules. It was found that bacterial capsules consist of acidic poly saccharides. From this it followed that the role of the capsules in the interaction of encapsulated bacteria with the host may be due to the chemistry of the capsular polysaccharides. This led to intensive studies of capsular polysaccharides in many laboratories. Our increasing knowledge of the structural features of capsular polysaccharides prompted not only immuno chemical studies analyzing the interactions of these poly saccharide antigens and characterizing the epitopes, but also investigations into their biosynthesis. These studies were complemented and supported by genetic analyses. Today many interdisciplinary investigations of capsular polysaccharides are in progress.