It has been recognized that viruses can induce neuronal damage by a variety of mechanisms. This volume summarizes, for the first time, the various ways that neurons can degenerate under the influence of viral infection, ranging from acute necrosis and virus-induced apoptosis to chronic damage in persistent infections. The mechanisms of neuronal latency are dealt with as well. The volume also includes chapters that review the chronic damage caused by viral proteins that interfere with differentiated functions of the neuron, including signaling by neurotransmitters and signal transduction by trophic factors. Other chapters deal with the controversial role of cellular immune reactions, which may be helpful in controlling infection, but may also be detrimental to the host nervous system. The specific mechanisms of damage involved in retroviral infections and in prion diseases of the nervous system are reviewed, and finally how autoimmune diseases can lead to neuronal damage.

This book provides a comprehensive, up-to-date review of the state of knowledge on the role of microbes in inducing autoimmune diseases. The initial chapters address the basic concept and clinical implications of immunology, while the following section discusses the role of genetics, epigenetics, hormones, stochastic and environmental factors in the pathogenesis of autoimmunity. The third section introduces readers to various autoimmune disorders and presents the cellular and molecular mechanisms of autoimmune diseases. In closing, the book examines the role of intestinal flora in the development of autoimmune diseases, delineates the underlying mechanism responsible for autoimmunity onset, and examines the potential of microbial therapeutics in the prevention and treatment of autoimmune diseases. Given its scope, the book offers a valuable asset for all scientists and clinicians working in immunology, rheumatology and autoimmune diseases.

During the last decade or so vaccine development has been facilitated by rapid ad- vances in the molecular and cell biology ofthe immune system. This has laid the foundations of a new generation of vaccines exemplified by subunit vaccines produced through gene cloning and by synthetic peptides mimicking small regions ofproteins on the outer coat ofvi- ruses. However, as subunit and peptide vaccines are only weakly or non-immunogenic, there is areal need for strategies to improve their potency. This book contains the proceedings of the 5th NATO Advanced Studies Institute (ASI), "Vaccine Design: The Role of Cytokine Networks," held at Cape Sounion Beach, Greece, during 24 June-5 July 1996 and deals in depth with the role ofbasic immunology in the regulation of immunity and vaccine design. Special emphasis is given to the use of cyto- kines in conjuction with vaccines with the aim ofimproving their potency or the use ofvac- cines designed to improve cytokine production. We express our appreciation to Dr. J.-L. Virelizier and Dr. G. Kollias for their cooperation in planning the ASI and to Mrs. Concha Perring for her excellent production ofthe manuscripts. The ASI was held under the sponsor- ship of NATO Scientific Affairs Division and generously co-sponsored by SmithKline Beecham Pharmaceuticals (Philadelphia). Financial assistance was also provided by Connaught Laboratories Ltd. (Ontario), Pasteur Merieux (Marcy I 'Etoile), Biochine (Siena), Help SA (Athens), and Avanti Polar Lipids Inc. (Birmingham, USA).

In recent years, the critical role of microRNAs has been revealed within the biology of cells that constitute the immune system. In MicroRNAs and the Immune System: Methods and Protocols, expert researchers explore the latest techniques for studying miRNA expression, including the most up-to-date data on splinted ligation and qRT-PCR assays, as well as high-throughput profiling through cloning, deep sequencing, and microarrays. Chapters outline methods to study miRNA functions in various cell types from a single cell type level to entire model organisms, and present studies of miRNAs in the context of viruses and the immune response. Tools are also provided to help navigate bioinformatics databases on miRNAs and their targets. Composed in the highly successful Methods in Molecular Biology (TM) series format, each chapter contains a brief introduction, step-by-step methods, a list of necessary materials, and a Notes section which shares tips on troubleshooting and avoiding known pitfalls. Contemporary and innovative, MicroRNAs and the Immune System: Methods and Protocols is an essential handbook for immunologists, biochemists, and molecular biologists.

This detailed book focuses on various aspects of Invariant Natural Killer T-Cells (iNKT), which are known to contribute to homeostasis and autoimmunity and can also cause various pathological responses such as allergy, infection, excessive autoimmune response, and cancer. The volume explores techniques for identification and isolation of iNKT cells, iNKT cell activation and transformation, as well as proliferation and differentiation and much more. Written for the highly successful Methods in Molecular Biology series, 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. Authoritative and practical, Invariant Natural Killer T-Cells: Methods and Protocols is an ideal guide for researchers working with and studying iNKT cells, perhaps to provide a deeper knowledge of the human immune system.

The immune system has been known to be capable of distinguishing self from non-self since the pioneering work of Paul Erhlich more than a century ago. Originally described in experiments studying blood transfusion comp- ibility, the principle of "horror autotoxicus" is still valid, although today the phenomenon is usually described in terms of tolerance or ignorance. A great deal has been learned about the various processes preventing self-reactivity normally. These include processes that operate during immune cell ontogeny and subsequently on reactivity of mature lymphocytes in the periphery. They encompass mechanisms that are intrinsic to potentially reactive lymphocytes and can result in central or peripheral deletion or the alteration of functional potential. In addition, there are in?uences that are extrinsic to potentially auto-reactive lymphocytes, including the function of regulatory cells, d- ferentiation state of antigen-presenting cells, availability of self-antigen, the cytokine and chemokine milieu, as well as the traf?cking patterns involved in generating productive immune interactions. It is clear that the immune system devotes a considerable effort to the avoidance of the development of potentially pathogenic self-reactivity. Despite this, the development of self-reactivity is relatively common. - though the development of autoimmune disease is less frequent, autoimmune diseases, such as rheumatoid arthritis, multiple sclerosis, systemic lupus e- thematosus, psoriasis, thyroiditis, and myasthenia gravis, are all too common, and can cause considerable morbidity and even mortality.

The recent developments in modern vaccinology are mainly based on: (i) cloning of microbial genes into recombinant vectors containing genetic information for expression of desired neutralizing immunogens; (ii) alternatives of attenuated vectors with deleted genes permitting the insertion of several foreign genes expressing antigens exposed to the host immune system during the abortive replication of such vectors; (iii) combined vaccines with the aim to protect against many diseases with a limited number of administrations; (iv) evidence demonstrating the ability of animals to respond serologically to DNA injections considered as a potential method of vaccination; (v) the possibility to manipulate the immune system with new and improved immunomodulators enhancing the immune response; and (vi) new microcarrier systems for particular immunogens or immunomodulators delivery, either in a single dose or sustained release, and presentation to the immune system for a relevant response. New vaccines being developed are mainly based on viral, bacterial or other vectors modified with genetic engineering technology, to possess and express desired antigens for vaccination against single or multiple infections. Existing combined vaccines like diphtheria, tetanus, pertussis (DTP) are also experimented with new additional components like recombinant hepatitis B virus surface antigen, inactivated poliovirus, and Haemophilus inJluenzae type b immunogens, in order to produce multivalent vaccines. Such types of vaccines permitting the reduction of multiple medical visits is of particular interest to pediatric immuni zation programs, and would benefit especially the developing countries assuring better vaccine compliance with immunization schedules."

A diverse team of leading experts comprehensively review the complex biology of a wide variety of vaccine combinations, as well as the technical, clinical, and regulatory aspects of their development. Topics covered range from the use of immunological correlates of efficacy, rather than efficacy per se, for the evaluation and licensure of vaccine combinations, to preserving a stable immunogenic mixture in appropriate containers according to accepted regulatory standards. Discussed in detail are the trivalent influenza vaccine, the pneumococcal polysaccharide vaccine, the MMR vaccine, the DTP vaccine and its combinations, and the quadrivalent rotavirus vaccine, all of which serve as models for the development of future combinations. Combination Vaccines: Development, Clinical Research, and Approval illuminates all the scientific, clinical, regulatory, and health care issues involved in the research, development, and human use of combination vaccines.

This volume discusses the vaccine development process and the role delivery concepts contribute to a global goal of effective health outcomes. The chapters in this book cover a wide range of topics such as antigen discovery methods; genetic and protein antigen preparation; preparation of viral vaccines as VLPs; viral and non-viral gene delivery; needle-less or non-invasive delivery technology; vaccine storage; and vaccine administration and assessment. 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. Cutting-edge and practical, Vaccine Delivery Technology: Methods and Protocols is a valuable resource for both novice and expert researchers, in and outside the field, who would like to gain insight into the impactful field of vaccines. Chapter 7 is available open access under a Creative Commons Attribution 4.0 International License via link.springer.com.

This second edition provides updated and new chapters to build on and extend the strengths of the first edition. Chapters guide readers through basic biology of basophils, obtaining the cells by purification, culture of stem cells progenitors, peripheral CD34+ stem cell-derived mast cells, basophils from CD34+ progenitors, diagnostic applications, gene expression patterns in basophils, roles of basophils in different asthma phenotypes, knockout, and disease models. 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. Authoritative and cutting-edge, Basophils and Mast Cells: Methods and Protocols, Second Edition aims to ensure successful results in the further study of this vital field.

This compilation presents mini-reviews derived from work presented at the Aegean Conference: "First Crossroads between Innate and Adaptive Immunity," which occurred in October, 2005 at the Hilton Conference Center on the island of Rhodes, Greece. The conference included sessions dedicated to host recognition of and response to pathogens, innate immune networks, antigen presentation, and adaptive immune responses, each headlined by a leading scientist.

The proposed book is envisioned for the nascent and entry-level researchers who are interested to work in the field of drug delivery and its applications specifically for macrophage targeting. Macrophages have gained substantial attention as therapeutic targets for drug delivery considering their major role in health and regulation of diseases. Macrophage-targeted therapeutics have now added significant value to the lives and quality of life of patients, without undue adverse effects in multiple disease settings. We anticipate examining and integrating the role of macrophages in the instigation and advancement of various diseases. The major focus of the book is on recent advancements in various targeting strategies using delivery systems or nanocarriers followed by application of these nanocarriers for the treatment of macrophage associated disorders. Macrophage Targeted Delivery Systems is primarily targeted to Pharmaceutical Industry & Academia, Medical & Pharmaceutical Professionals, Undergraduate & Post graduate students and Research Scholars, Ph.D, post docs working in the field of medical and pharmaceutical sciences.

This book discusses prospective alternative approaches to fight bacterial infections to minimize the indiscriminate use of conventional antibiotics. It offers the current knowledge on research and development of alternative antibacterial agents such as probiotics, nanobiotics etc. while it also discusses newly emerging trends such as phage therapy, antibody therapy etc. The book highlights on the phytochemicals with potent antibacterial activities as alternatives to conventional antibiotics. Chemical modification to develop next generation antibiotics with enhanced efficacy has also been included. Such modifications are reported to overcome the inherent resistance of the parent antibiotics. Phage therapy and targeted antibodies are considered as potential alternative approaches to treat bacterial ailments and represent areas of cutting-edge research and have therefore been discussed with sufficient care. Mainly, the book highlights various approaches other than conventional antibiotics in treating bacterial infections. The scientific advancements in these areas will strengthen the 'One Health' approach benefiting human beings, animals and environment as well. This book is a comprehensive resource to cater researchers, biological scientists, herbalists and clinical practitioners with up-to-date information on antibacterials other than antibiotics.

Combination Immunotherapy: Immune Therapy of Human Cancers (R.P. Gale, A. Butturini). Clinical Applications of Combination Chemoimmunotherapy in Cancer: Combination of Fluorouracil and Interfon (R. Pazdur). Combination Approaches and Gene Therapy in the Treatment of AIDS and Other Infectious Diseases: Combination Therapies with Cytokines and AntiCytokines in Murine Opportunistic Infections (L. Romani et al.). Mechanism of Action and Synergy Between Drugs, Biological Response Modifiers and/or Vaccines in Combination Therapies: The Case for Synergy of Thymic Hormones and Interleukins in Immune Reconstitution (J.W. Hadden et al.). Immune Mediated Tumor Destruction (P.M. Sondel). Prospects and Future Directions Using Animal Models to Define Effective Combination Therapies with Biological Response Modifiers: Cancer Immunotherapy (L. Tentori et al.). 29 additional articles. Index.

This biography of Dr. Denis Parsons Burkitt, after whom the childhood cancer Burkitt's lymphoma was named, and who was a pioneer of the dietary fiber movement, paints a personal but holistic portrait of both the man and his life's work. Featuring excerpts from Dr. Burkitt's personal diaries, spanning seven decades from his boyhood to just before his passing, and extensive family archives, this book invites readers to follow Burkitt's journey through life and experience his tribulations and successes. Prof. John Cummings was a colleague of Dr. Burkitt and weaves the tale of his life through the lens of family, faith, and science. The journey takes Burkitt from his childhood in Ireland, a country undergoing major social upheaval, through his medical studies in Dublin, to army service in Africa in the midst of WWII and the independence movements that swept the continent in the following years. During his two decades spent in Uganda, working for the Colonial Medical Service, Burkitt made his first major contribution to cancer research - the characterization of Burkitt's lymphoma and its possible viral cause. Following his return to England in 1966, he turned his attention to the cause of 'Western Diseases' especially the role of dietary fibre in the prevention of disease and promotion of health. This earned him even wider international recognition and helped to inspire what is a vital field of research today. The book examines Burkitt's personal views of the world around him, including his experiences as a committed evangelical Christian who had been raised an Irish Protestant, and the challenges, both familial and cultural, that this elicited from and towards him and his scientific work. The lymphoma and later the fibre story propelled Denis into an orbit of worldwide travel, fame and many honours. An engaging speaker but man of great humility, always giving the credit for much of what he did to others, he left a legacy of evidence and ideas for the causes of cancer and prevention of disease from which we all now benefit.

Allergy is an immunological disease caused by multiple factors and characterized by variability, specificity and complexity. "Multidisciplinary Approaches to Allergies" covers diverse aspects ranging from basic molecular mechanisms to societal issues within the framework of multidisciplinary approaches to allergies. It contains 29 chapters in 6 parts: General Allergy; Allergenic Sources and Allergens; Diagnosis; Therapies and Pharmacy; Hypoallergenic Products; Environment, Hygiene and Societal Issues. It can be used in education and research as introductory and supplementary material. It is also an indispensable tool for scientists and doctors who are searching for an integrated way for allergy prevention, treatment and management.

Zhong-Shan Gao, Ph.D., is Professor of Fruit Science and Allergy at the Department of Horticulture and the Allergy Research Center, Zhejiang University, China. Hua-Hao Shen, M.D., Ph.D., is Professor of Respiratory Diseases at the Second Affiliated Hospital, School of Medicine, Zhejiang University, China, and Professor in the Chang Jiang Scholars Program (MOE). Min Zheng, M.D., Ph.D., is Professor of Dermatology at the Second Affiliated Hospital, School of Medicine, Zhejiang University, China. Lynn J. Frewer, Ph.D., is Professor of Food & Society at the School of Agriculture, Food and Rural Development, Newcastle University, UK. Luud J.W.J. Gilissen, Ph.D., is senior researcher at Plant Research International, Wageningen University and Research Centre, the Netherlands.

This detailed book provides a broad collection of methodologies for natural killer (NK) cell research. Beginning with an assortment of methods for the isolation of NK cells and NK cell differentiation, the volume continues with methodologies for functional tests, such as cytotoxicity, viral infection, and metabolism assays, as well as clinical applications of NK cells. Written for the highly successful Methods in Molecular Biology series, 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. Authoritative and practical, Natural Killer (NK) Cells: Methods and Protocols serves as an ideal guide for researchers looking to contribute to the further development of basic and clinical NK cell research.

Reproductive Immunology is a growing area in both immunology and reproductive sciences and is helping us to better understand several complications of pregnancy. Immunology of Pregnancy is the first book to give a complete and up to date review of our knowledge related to the role of the immune system during pregnancy and the interactions between the placenta and the maternal immune system. This new title covers in detail all the different hypotheses and studies related to the immunology of implantation and provide a practical approach for the application of basic reproductive immunology research to pregnancy complications such as preeclampsia, pre-term labor and IUGR."

The complement system is a group of proteins which plays a major role in the processing and removal of microorganisms and tissue breakdown products from the circulation and extracellular spaces. The system is activated by a wide range of targets, and activation leads to the production of opsonins, chemotaxis of granulocytes, cell lysis and other biological activities. Inappropriate overactivation of the system contributes to inflammatory tissue damage in the host, while inadequate activation leads to accumulation of immune complexes and other debris in the circulation, and susceptibility to infection. The biology and biochemistry of the system is now adequately understood, and attempts can be made to manipulate the activation and activities of the system for potential therapeutic purposes. The reviews in this volume summarise what is known of the ways in which the complement system can be activated, by interaction with antibodies, microorganisms, cell debris, and complex carbohydrates and how the activities and activation of the system have been modified, accidentally or by design, in vitro or in vivo by drugs, venoms, particulate carbohydrates, specific antibodies, synthetic peptides and other reagents.

HPV Gene Expression: The Antibody Response Against p53 in Cancer Patients (G. Matlashewski). Enhanced Production of WildType p53 Inhibits Growth and Differentiation of Normal Foreskin Epithelial Cells but not Cell Lines Containing Human Papillomavirus DNA (C.D. Woodworth et al.). Humoral Responses to HPV: Humoral Immune Response to Genital Human Papillomavirus Infections (L. Gissman). HPV 16 Antibodies in Cervical Cancer Patients and Healthy Control Women (V. Vonka et al.). Cell Mediated Immunity to HPV: Evolution of Class I HLA Antigen Presenting Molecules (P. Parham). Major Histocompatibility Complex Expression and Antigen Presentation in Cervical Cancer (J.S. Bartholomew et al.). Animal Models and Therapeutic Strategies: Skin Test Reactivity to Papilloma Cells Is Long Lasting in Domestic Rabbits After Regression of Cottontail Rabbit PapillomavirusInduced Papillomas (R.M. Hoepfl et al.). 42 additional articles. Index.

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.

Both nutrition deficiency and overnutrition can have a significant effect on the risk of infection. Nutrition, Immunity, and Infection focuses on the influence of diet on the immune system and how altering one's diet helps prevent and treat infections and chronic diseases. This book reviews basic immunology and discusses changes in immune function throughout the life course. It features comprehensive chapters on obesity and the role of immune cells in adipose tissue; undernutrition and malnutrition; infant immune maturation; pre- and probiotics; mechanisms of immune regulation by various vitamins and minerals; nutrition and the aging immune system; nutrition interactions with environmental stress; and immunity in the global health arena. Nutrition, Immunity, and Infection describes the various roles of nutrients and other food constituents on immune function, host defense, and resistance to infection. It describes the impact of infection on nutritional status through a translational approach. Chapters bring together molecular, cellular, and experimental studies alongside human trials so that readers can assess both the evidence for the effects of the food component being discussed and the mechanisms underlying those effects. The impact of specific conditions including obesity, anorexia nervosa, and HIV infection is also considered. Chapter authors are experts in nutrition, immunity, and infection from all around the globe, including Europe, Australia, Brazil, India, and the United States. This book is a valuable resource for nutrition scientists, food scientists, dietitians, health practitioners, and students interested in nutrition and immunity.

The concept of using bispecific antibodies for cancer therapy by retargeting immune effector cells was developed several years ago. Initial clinical studies were rather disappointing mainly due to low efficacy, severe side effects and the immunogenicity of the bispecific antibodies. The progress in antibody engineering finally led to the generation of new classes of bispecific antibodies lacking these obstacles. In addition, new applications were established, such as pre-targeting strategies in radioimmunotherapy and dual targeting approaches in order to improve binding, selectivity and efficacy.

In this book, the different ways of generating bispecific antibodies are described, with emphasis on recombinant formats. The various applications of bispecific antibodies, e.g. in cellular cancer immunotherapy, radioimmunotherapy and pretargeting strategies are covered, and emerging applications such as dual targeting strategies, which involve the simultaneous inhibition of two targets, are addressed.

This book represents an evolutionary approach to defense mechanisms of all living organisms. The results achieved in developmental and comparative immunology are among the most interesting data in immunology. These results have great impact on our understanding fundamental problems of the pathology of the human immune system. At the same time, the field of evolutionary immunology provides not only inspiration for further investigation in biomedicine, but also a number of results applicable in clinical and commercial practice.

This book evaluates the advantages and limitations of studying the development of defense reactions. In addition to reviewing the major and crucial achievements of the past, the book offers a comprehensive state-of-the-art treatise focused primarily on the latest experiments described in the last few years.