M. BENcovA Slovak Foundation Education in Immunogenetics Kopanice 25, 821 04 Bratislava Slovak Republic Short History of Slovakia After the end of the 5th century, the major part of Central Europe was dominated by Slavs (Slovaks). They had already in the 7th century settle ments in the vicinity of towns Bratislava, Devin, Nitra to create the Slovak's state formation with the name "The Empire of Sam", territory of which corresponded to that of Slovakia of present. The Empire of Sam was also the first state formation in the Central Europe (as present states Czech Republic, Poland, Hungary, Slovakia etc. ) Very important town of this state was Nitra, with the biggest Castle in the Central Europe with his Duke Pribina. The first Church of the Central Europe was built here in the year 830, and it is now considered to be the "Slovak Bethlehem". In the year 880, Nitra also became the first Office of Bishops. Later, the Slovak Duke Pribina and Moravian Duke Mojmir (Moravia corresponded to eastern part of the present Czech Republic) joined their formations to common state "Greate Moravian Empire". The strongest King of the Great Moravian Empire was Svatopluk (864 A. D. ), who spread his empire over Czech Republic, Hungary and part of Poland, Ukraine and eastern Germany of present, which at that time still did not exist as state formations.

"Immuno Systems Biology" aims to study the immune system in the more integrated manner on how cells and molecules participate at different system levels to the immune function. Through this bookKumar Selvarajoointroduces to physicists, chemists, computer scientists, biologists and immunologists the idea of an integrated approach to the understanding of mammalian immune system. Geared towards a researcher with limited immunological and computational analytical experience, the book provides a broad overview to the subject and some instruction in basic computational, theoretical and experimental approaches. The book links complex immunological processes with computational analysis and emphasizes the importance of immunology to themammalian system. "

Cell adhesion - the attachment of cells to any surface such as other cell membranes or tissues - is a complex process. In many physiological and pathological processes adhesion of a cell is the first critical step.
A wide spectrum of the most powerful techniques currently available to study the basic parameters of cell adhesion, including binding strength, binding efficiency, membrane-membrane or membrane-substrate interaction, structural properties and dynamics of cell surface molecules, is presented in this strategy book. Sophisticated quantitative approaches as well as comprehensible semi-quantitative methods are described. The detailed theoretical background allows the critical assessment and application of these techniques.

With a long practice of organ transplantation, retransplantation has become a major goal in patients with long-term failure of their first transplant (chronic rejection, exhaustion of the transplant, recurrence of the initial disease, etc. ). In addition, retransplantation can be necessary in the initial period, due to severe acute rejection, a non-functioning organ, or surgical complication. Immunological and non-immunological factors affecting the success of a second transplant are described in this volume, together with alternatives to retransplantation. It is hoped that in the future retransplants will be less frequent, as a result of improved prevention of transplant failure. J. L. Torrroine et a/. (ens. ), Retra isplantation, xvii. Q 1997 Kluwer Academic Pirblislters. P . iilted in Great Britain. List of contributors R. ARNOLD Y. W. CHO University of Pittsburgh UCLA School of Medicine Center for Medical Ethics Tissue Typing Laboratory Division of General Internal Medicine 950 Veteran Avenue 200 Lothrop Street - MUH, Suite W-919 Los Angeles, CA 90095-1652 Pittsburgh, PA 15213-2582 USA USA P. COCHAT M. A. BELGER Hopital Edouard Herriot UKTSSA Pavillon S Fox Den Road 5, Place d'Arsonva1 Stoke Gifford F-69437 Lyon Cedex 3 Bristol BS12 5RR France UK B. CUZIN F. BERTHOUX Hopital Edouard Herriot Service de Nephrologie et Pavillon V Transplantation Renale 5, Place d3Arsonval Hopital Nord F-69437 Lyon Cedex 3 F-42055 Saint Etienne Cedex 2 France France J. H. DAUBER C.

Borna disease was first described over 200 years ago, in what is now Southeastern Germany, as a fatal neurologic affliction of horses and was considered a curiosity for many decades. The causative agent was unknown, and the animal species infected in nature were limited to horses and sheep. Today, as described in this volume, the host range has extended to all warm-blooded animals, the genes and proteins of the virus have been identified, and many of the mechanisms responsible for behavioral disturbances are understood. Serologic studies suggest that BDV or related agents are likely to play a role in human neuropsychiatric diseases.

Diseases of the gastrointestinal tract are common. There is increasing appreciation of the importance of the immune system in the pathogenesis of a number of these diseases. This book covers basic aspects of innate and adaptive immunity in the gastrointestinal tract, oral tolerance, and cellular and molecular mechanisms of acute and chronic inflammation. Specific disease covered include bacterial infections, human immunodeficiency virus (HIV) infection, coeliac disease, and inflammatory bowel disease. Other topics include mucosal immunisation and intestinal transplantation immunology. The readership of this book includes clinicians, scientists, and students interested in the gastrointestinal tract.

In 1986, the Committee of Experts on Blood Transfusion and Immunohae- tology of the Council of Europe chose for their Programme of Co-ordinated Research "An investigation of the procurement and sharing of transplantable organs for potential recipients who are highly sensitized to HLA-antigens." This topic was of common concern to all centres practising renal transplan- tion. The terms of reference of the study were: To estimate the number of patients who are virtually "untransplantable" because of high sensitization in each European country. To study the nature of immunization in terms of the type and specificity of antibodies present in the blood and techniques used for their detection. To investigate possible practical solutions - both current and future, invo- ing cross-matching procedures, the circulation of reference material from patients, and the willingness of the national organizations to share resources. 4. To explore other methods of resolving this problem. Although the study did not offer the prospect of a brilliant new insight into the problem of high sensitization, it was unique in several ways: for the first time we saw all European organizations collaborating in a common project to provide information on their activities, their problems and the methods to resolve them; it introduced, for this subject, relatively novel statistical methods to investigate susceptibility to sensitization and factors affecting transplant outcome; it enabled a large database of transplanted highly sensitized patients and matched controls to be assembled, that would have been unavailable as a research resource at any single centre.

9. Wright, D. J. M. (1980). Reaction following treatment of murine borreliosis and Shwartzman type reaction with borrelial sonicates. Parasite Immunol. , 2, 201-21 10. Tekli. l, B. , Habte-Michal, A. , White, N. J. , Warrell, D. A. and Wright, D. J. M. (1983). Meptazinol diminishes the Jarisch-Herxheimer reaction. Lancet, 1, 835-9 II. Wright, D. J. M. (1973). The significance of the fluorescent treponemal antibody (FTA- ABS) test in collagen disorders and leprosy. J. Clin. Pathol. , 26, 968-72 12. Noguchi, H. (1911). A cutaneous reaction in syphilis. J. Exp. Med. , 14, 557-68 13. Frei W. (1925). Eine neue hautreaktion bei 'lymphogranuloma inguinale'. Klin. Wochenschr. , 4, 2148-9 14. Murray, J. F. , Felton, C. P. , Garay, S. M. et al. (1984). Pulmonary complications of the acquired immunodeficiency syndrome. Report of a National Heart, Lung and Blood Institute workshop. N. Engl. J. Med. , 310, 1682-8 15. Ehrmann, S. (1907). Versuche uber autoinfektion bei syphilis. Verh. Dtsch. Dermatol. Gesel Berl. , 1,265-70 16. Gluck, A. , cited by Grin E. 1. (1953). Epidemiology and control of endemic syphilis: report on mass treatment campaign in Bosnia. Monograph I I, pp. 34-5. (Geneva: WHO) 17. Neisser, A. , cited by Chesney, A. (1926). Immunity in syphilis. Medicine (BaIt. ), 5,463-87 18. Grimble, A. and Lessof, M. H. (1965). Anti-prostate antibodies in arthritis. Brit. Med. J. , 11, 263-4 xiii 1 Syphilis S. J.

The availability of powerful genome-wide association study technology, during the last five years, has shown that most of the "new" MS susceptibility loci are immune-response genes. It is clear that there is much novelty in the field of MS immunology, which has served as an impetus to invest in new therapies. Notably, most if not all of these are immunotherapies. Even the equally exciting field of cell-based therapies and neuro-regeneration may well rely on cells or growth factors that are no less immunomodulators than restorative of myelin and neural cell function. Multiple Sclerosis Immunology looks at MS immunology as the basis for the present and-even more-the future of treatments for this complex autoimmune condition. Both editors are immunologists, as well as clinical neurologists, and appreciate the importance of a sustained dialogue between basic and clinical scientists to ensure that "translation" is real and not just virtual.

The introduction of monoclonal antibodies revolutionized immunology. The development of human monoclonal antibodies was inspired primarily by the enormous clinical benefits promised by these reagents which can be used as anti-inflammatory reagents, anti-tumor reagents and reagents for passive immunization in a variety of pathologies. Human Monoclonal Antibodies: Methods and Protocols presents technical protocols of cellular and molecular methods for the production, purification and application of human monoclonal antibodies, as well as review articles on related topics of human monoclonal and polyclonal antibodies. Written in the successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and easily accessible, Human Monoclonal Antibodies: Methods and Protocols seeks to serve both professionals and novices with its well-honed methodologies which will prove invaluable in a clinical setting.

The phenomena involved in infections of man and domestic animals with metazoan or protozoan parasites present formidable practical problems as well as a theoretical challenge to immunologists, molecular biologists, and evolu tionary biologists. With respect to the public health and economic problems, malaria, for example, remains a major health problem with approximately 200 million people being infected yearly and, on the basis of World Health Organiza tion estimates, more than 1 million children die each year of malaria infections (Chapter 4). This volume addresses state-of-the-art immunologic approaches to the development of vaccines for parasitic diseases (Chapter 9) and analyses of studies bearing on the antigenic characterization of protozoan and metazoan parasites (Chapters 4, 5, and 7), on investigations of the role of precise mecha nisms underlying natural resistance or non permissiveness of the host to parasitic infections (Chapters 1, 2, and 12), on induced mechanisms including the genera tion of parasite-specific T-cell lines and clones (Chapter 6), and on the generation of monoclonal antibodies (Chapters 4 and 5) to parasite antigens of distinct de velopmental stages. Great progress has been made in characterizing parasite antigens capable of inducing a protective response in the vaccinated host; further progress in this area strongly depends on biochemistry and molecular biology with the long-term goal of synthesizing such antigens chemically or producing them by means of recombinant DNA technology (Chapter 4).

Leishmania-related illnesses remain among the world s deadliest neglected tropical diseases, affecting approximately 12 million people in 88 countries.The mortality rate is substantial, contributing to nearly two million disability-adjusted life years. As more is understood about this parasite and its effects, work toward prevention, control, and treatment continues apace."Leishmania and Leishmaniasis" will address the parasite and its attendant disease, which manifests in three syndromes: Visceral (VL), Cutaneous (CL) and Mucocutaneous Leishmaniasis (ML). The morphology and life cycles of the various species will be among the topics addressed in Part One. Part Two will focus on immunology, including host-immune response to Leishmania infection, cross-immunity between the different species and adoptive transfer of immunity. Parts Three and Four will address how Leishmania invade and survive, the clinical features of the disease, and its diagnosis.Drugs, vaccines and treatment will be thoroughly explored, including experimental models of therapeutics. "Leishmania and Leishmaniasis" will provide a thorough examination of a parasite, the illnesses it causes and the misery it continues to visit upon large segments of the population. "

Immunology has come a long way in the hundred or so years since the general concepts were first enuciated by Metchnikoff, Ehrlich, Von Bebring and others, One of the landmarks in this progress was the invention and development of monoclonal antibody secreting hybridomas by Milstein and bis co-workers in Cambridge. Unlike most modern inventions of this importance that of monoclonal antibody production was made available to the scientific community tbroughout the world unimpeded by patent protection. This may explain tbe unusual rapidity witb which it has been applied to the benefit of mankind in general. This book, representing as it does the proceedings of tbe first International Symposium to be held on the clinical appli cations of monoclonal antibodies, shows just how much bas been achieved within the space of little more than a decade. The enormaus promise of monoclonal antibody technology, which became apparent soon after its discovery, has already progressed a long way towards fulfillment. The contributors to tbis volume, all of whom are actively engaged in monoclonal antibody development and application, represent the state of the art. Professor Vincent Marks V INTRODUCTION It has been some twelve years since the pioneering experiments of Koehler and Milstein led to the discovery of monoclonal antibodies. Single molecular species antiborlies with desired specificities could be produced by the fusion of antibody - producing cells with neoplastic cells.

This book offers comprehensive information on the polymorphisms of genes encoding pattern recognition receptors (PRRs). Following a short description of the general role of PRRs in the immune system, the structure and function of Toll-like and NOD-like receptors are examined in detail. The main focus is on the role of inherited variation in PRRs and their correlation to cancer and cardiovascular diseases. A review of all epidemiological investigations is included, and a concept of genomic risk markers for the prevention of various diseases is also discussed.

The immune systems of human and non-human primates have diverged over time, such that some species differ considerably in their susceptibility, symptoms, and survival of particular infectious diseases. Variation in primate immunity is such that major human pathogens - such as immunodeficiency viruses, herpesviruses and malaria-inducing species of"Plasmodium"- elicit striking differences in immune response between closely related species and within primate populations. These differences in immunity are the outcome of complex evolutionary processes that include interactions between the host, its pathogens and symbiont/commensal organisms. The success of some pathogens in establishing persistent infections inhumans and other primateshas been determined not just by the molecular evolution of the pathogen and its interactions with the host, but also by the evolution of primate behavior and ecology, microflora, immune factors and the evolution of other biological systems.

To explore how interactions between primates and their pathogenshave shaped their mutual molecular evolution, "Primates, Pathogens and Evolution"brings together research that explorescomparativeprimate immune function, the emergence of major and neglected primatediseases, primate-microorganism molecular interactions, and related topics. Thisbookwill be of interest to anyone curious as to why infectious diseases manifest differently in humans and their closest relatives. It will be of particular interest to scholars specializing in humanand non-human primate evolution, epidemiology and immunology, and disease ecology."Primates, Pathogens and Evolution"offers anoverview and discussion of current findings on differences in the molecular mechanics of primate immune response, as well as on pathogen-mediated primate evolution and human and non-human primate health."

The first libraries of complementary DNA (cDNA) clones were con structed in the mid-to-late 1970s using RNA-dependent DNA polymerase (reverse transcriptase) to convert poly A* mRNA into double-stranded cDNA suitable for insertion into prokaryotic vectors. Since then cDNA technology has become a fundamental tool for the molecular biologist and at the same time some very significant advances have occurred in the methods for con structing and screening cDNA libraries. It is not the aim of cDNA Library Protocols to give a comprehensive review of all cDNA library-based methodologies; instead we present a series of up-to-date protocols that together should give a good grounding of proce dures associated with the construction and use of cDNA libraries. In deciding what to include, we endeavored to combine up-to-date versions of some of the most widely used protocols with some very usefiil newer techniques. cDNA Library Protocols should therefore be especially useful to the investigator who is new to the use of cDNA libraries, but should also be of value to the more experienced worker. Chapters 1-5 concentrate on cDNA library construction and manipula tion, Chapters 6 and 7 describe means of cloning difficult-to-obtain ends of cDNAs, Chapters 8-18 give various approaches to the screening of cDNA libraries, and the remaining chapters present methods of analysis of cDNA clones including details of how to analyze cDNA sequence data and how to make use of the wealth of cDNA data emerging from the human genome project.

This book describes how the Jerne-Burnet Forbidden Clone Theory and the Adams-Knight H Gene Theory, solved the pathogenesis and genetics of the autoimmune diseases showing how specific immunotherapy and prophylaxis can be developed. Furthermore, Ebringer's discovery of two microbial triggers of autoimmune diseases is described and the conclusion drawn that all autoimmune diseases have microbial triggers, so will be preventable by the finding of the triggers and vaccination against them.

Providing current diverse approaches and techniques used to study the immunoproteome, Immunoproteomics: Methods and Protocols collects chapters from key researchers that deliver information to be used in diagnostics, disease progression, and vaccine correlates of protection analysis, to name but a few. This detailed volume includes techniques used for the study of the antibody targets of bacterial pathogens, viruses, and cancer, mass spectrometry-based approaches to characterize T-cell epitopes, chapters on detection and relative quantification of cytokines in serum, as well as in silico prediction of epitopes using sequence-based or modeling approaches. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Practical and thorough, Immunoproteomics: Methods and Protocols aids researchers in transferring these techniques to their own laboratories in addition to providing a reference to guide researchers toward appropriate techniques.

Viral Vaccines Joseph L. Melnick As with history in general, the history of vaccines needs to be reexamined and updated. My task is to look back to see what has been successful and to look forward to see what remains to be accomplished in the prevention of viral diseases by vaccines. Also, I shall refer to the pertinent material discussed at two recent conferences of the Institute of Medicine, National Academy of Sciences, on virus vaccines under development and their target populations in the United States (1985b) and in developing countries (1986). These reports, plus a third on Vaccine Supply and Innovation (1985a), should be required reading for all those in both the public and the private sector who have a responsibility or interest in vaccines for the prevention of human disease. It has been through the development and use of vaccines that many viral diseases have been brought under control. The vaccines consist either of infectious living attenu ated viruses or of noninfectious killed viruses or subviral antigens. When we look at the record, it is the live vaccines that have given the great successes in controlling diseases around the world. Examples are smallpox, yellow fever, poliomyelitis, measles, mumps, and rubella."

The difficulty in achieving effective translation of basic mechanistic biomedical knowledge into effective therapeutics, is the greatest challenge in biomedical research. Nowhere is this more apparent than in the reductionist approaches to understanding and manipulating the acute inflammatory response in the settings of sepsis, trauma/hemorrhage, wound healing, and related processes. This book discusses complex systems and computational biology methods and approaches that have advanced sufficiently to allow for knowledge generation, knowledge integration, and clinical translation in the settings of complex diseases related to the inflammatory response. Well-regulated, self-resolving inflammation is necessary for the appropriate communication and resolution of infection and trauma, and for maintenance of proper physiology and homeostasis. In contrast, self-sustaining inflammation drives the pathobiology of the aforementioned diseases. It is now increasingly recognized that controlling and reprogramming inflammation in order to reap the benefits of this evolutionarily-conserved process is preferred to simply abolishing indiscriminately.

Superantigen Protocols assembles experimental protocols that have proved useful for the study of superantigens. These techniques will allow researchers from various areas of cell biology, microbiology, immunology, biochemistry, and molecular biology to assess the physical characteristics and biological effects of well-known superantigens as well as of putative substances that might have superantigenic activities, and to explore therapies for superantig- induced effects. Microbial exotoxins have been studied for decades as virulence factors because of their pathogenic effects. The term "superantigen" was coined by Marrack and Kappler a decade ago for some of these molecules because of their potent T-cell stimulatory activities. In recent years, advances in mole- lar biology provide recombinant as well as natural superantigens in highly purified form for physical characterization. Superantigens are now used extensively as tools to study interactions between receptors on cells of the immune system as they bind to major histocompatibility complex class II m- ecules on antigen-presenting cells and V regions of T-cell receptors. The b- ? logical effects that result from these interactions are studied both in vitro and in vivo. The intent of this book is, therefore, to bring together up-to-date te- niques developed by experts in the field of biochemistry, immunology, and molecular biology for the study of superantigens. Superantigen Protocols begins with an overview of the field to provide background information on the various classes of superantigens and their str- ture.

The aim of MHC Protocols is to document protocols that can be used for the analysis of genetic variation within the human major histocompatibility complex (MHC; HLA region). The human MHC encompasses approximately 4 million base pairs on the short arm of chromosome 6 at cytogenetic location 6p21. 3. The region is divided into three subregions. The telomeric class I region contains the genes that encode the HLA class I molecules HLA-A, -B, and -C. The centromeric class II region contains the genes encoding the HLA class II molecules HLA-DR, -DQ, and -DP. In between is the class III region, originally identified because it contains genes encoding components of the complement pathway. The entire human MHC has recently been sequenced (1) and each subregion is now known to contain many other genes, a number of which have immunological functions. The study of polymorphism within the MHC is well established, because the region contains the highly polymorphic HLA genes. HLA polymorphism has been used extensively in solid organ and bone marrow transplantation to match donors and recipients. As a result, large numbers of HLA alleles have been identified, a process that has been further driven by recent interest in HLA gene diversity in ethnic populations. The extreme genetic variation in HLA genes is believed to have been driven by the evolutionary response to infectious agents, but relatively few studies have analyzed associations between HLA genetic variation and infectious disease, which has been difficult to demonstrate.

This Methods in Molecular Biology book offers methods for studying inflammasome function, including generation of inflammasome stimuli, monitoring of caspase-1 activity and processing, activation of IL-1 cytokines, plus lab protocols, material lists and tips.