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Book T Lymphocyte and Inflammatory Cell Research in Asthma

Download or read book T Lymphocyte and Inflammatory Cell Research in Asthma written by G. Jolles and published by Academic Press. This book was released on 2012-12-02 with total page 391 pages. Available in PDF, EPUB and Kindle. Book excerpt: It is well established that asthma is an inflammatory disease of the airway mucosa and drugs like inhaled glucocorticoids are now commonly introduced early in therapy. A characteristic feature of this disease is the vast number of eosinophils in airway tissue, although many other migratory and resident inflammatory cells with the capacity to synthesize and release cytokines and putative asthma mediators are present in the inflamed mucosa. The cross-talk between lymphocytes and these cells and the role of cytokines in complex biological networks are currently areas of intense research. This volume gathers together chapters and discussions on the biology of immunocompetent and inflammatory cells, cellular interplay and communication, and on the relative importance of cells and mediators in disease. It should help contribute to further insights into the pathology of asthma and to the development of novel efficacious drugs for the treatment of asthma and related respiratory disorders.

Book The Immunological Basis of Asthma

Download or read book The Immunological Basis of Asthma written by Bart Lambrecht and published by CRC Press. This book was released on 2003-02-26 with total page 711 pages. Available in PDF, EPUB and Kindle. Book excerpt: This text assesses the role of dendritic cells, T and B lymphocytes, epithelial and mast cells, eosinophils, neutrophils, macrophages, and their products in the initiation and progression of airway inflammation, regulation, and repair. It unveils advances in immunology and cell biology to generate new therapeutic regimens for inflammatory and aller

Book T Cell Regulation in Allergy  Asthma and Atopic Skin Diseases

Download or read book T Cell Regulation in Allergy Asthma and Atopic Skin Diseases written by Kurt Blaser and published by Karger Medical and Scientific Publishers. This book was released on 2008-01-01 with total page 243 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book presents the state of the art in cellular and molecular mechanisms regulating the immune response in allergic inflammation. Special attention is given to the central role of regulatory T cells (Treg) in immune regulation and induction of peripheral tolerance, as well as to the relevance of Th17 cells in chronic inflammation. The importance of Treg and Th17 cells is demonstrated in bronchial asthma, atopic eczema, contact dermatitis and delayed-type hypersensitivity. Furthermore, T-cell-mediated regulatory mechanisms in helminthic infections and fungal allergy are discussed. Several chapters are devoted to the therapeutic consequences that these recently discovered T-cell functions may have. Their role as a potential target for specific immunotherapy is evaluated and novel approaches for peripheral tolerance induction and treatment of allergic and asthmatic diseases and inflammation are suggested. Stem cell transplantation as a future therapeutic intervention in regulatory T-cell disorders is also considered. Well edited and up to date, this volume is recommended reading for allergologists, immunologists, dermatologists and any scientist interested in the immunological events regulating allergic inflammation in general and allergic manifestations in different organs.

Book Inflammatory Cells and Mediators in Bronchial Asthma

Download or read book Inflammatory Cells and Mediators in Bronchial Asthma written by Devendra K. Agrawal and published by CRC Press. This book was released on 2020-10-28 with total page 268 pages. Available in PDF, EPUB and Kindle. Book excerpt: Inflammatory Cells and Mediators in Bronchial Asthma provides reviews and summaries regarding state-of-the-art articles that examine the role of various inflammatory cells and their mediators in the pathogenesis of asthma. Topics include pharmacological and biochemical regulation of the airways; involvement of key inflammatory cells and the release and effect of their mediators in airway function; and the characteristics of receptors for leukotriene B4, C4, and D4, adenosine, platelet-activating factor, sensory and inflammatory peptides, and the effect of various anti-asthmatic drugs on airway inflammation. Physicians, allergists, immunologists, and pulmonary disease research scientists will find this book to be an invaluable reference resource.

Book Role of CD4 T cell sub populations in allergic asthma

Download or read book Role of CD4 T cell sub populations in allergic asthma written by Shakti P. Pattanayak and published by GRIN Verlag. This book was released on 2016-07-27 with total page 47 pages. Available in PDF, EPUB and Kindle. Book excerpt: Scientific Essay from the year 2016 in the subject Medicine - Pharmacology, Pharmacy, , language: English, abstract: Asthma is a chronic disorder specifically characterized by severe inflammation and constriction, mucus hyper-secretion and hyper-responsiveness in the airway. Allergic Asthma (AA) is characterized by discontinuous airway obstruction that may cause temporary to severe asphyxiation and can consequence into death. Airway obstruction in asthma is because of rigorous inflammation concerning multi-cellular components together with eosinophils, neutrophils, CD4+T lymphocytes & mast cells, with eosinophilic infiltration being the most conspicuous feature. The multifaceted phenotype of AA suggested being elevated from multiple interactions of infiltrating and structural cells that is coordinated by T helper 2 (TH2) cells consequential in chronic airway inflammation. By extremely secreting convinced mediators like interleukin (IL)-4, IL-5, and IL-13, which grasps a key point in asthma pathogenesis cause erratic degree of broncho-obstruction, increased mucus production, and airway remodeling. There are a variety of T cell which plays a significant role in AA that is TH1, TH2, TH17, regulatory T cell, TH3 TH22, TH25, TH9 and others. There are various molecular signaling molecules such as STAT4, FOXp3, GATA-3 and T-bet which regulates CD4+T cells in AA. Nowadays the approach to manage asthma is based on inhaled bronchodilator and corticosteroids. But the research is on the mechanism of some promising phytomedicines. we summarized here with some mechanisms of some flavonoids to alleviate AA through CD4+T cells. In conclusion, we found that the CD4+T-cell subpopulations played some major contribution in regulating/modulating the AA and interestingly, the natural potent anti-oxidant & anti- inflammatory compounds such as flavonoids could able to attenuate the AA by regulating these subpopulations of CD4+T-cells or the signaling molecules involved in the pathogenesis.

Book Immunotherapy in Asthma

    Book Details:
  • Author : Jean Bousquet
  • Publisher : CRC Press
  • Release : 1999-08-24
  • ISBN : 9780824701765
  • Pages : 0 pages

Download or read book Immunotherapy in Asthma written by Jean Bousquet and published by CRC Press. This book was released on 1999-08-24 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: This massive reference thoroughly analyzes the mechanisms implicated in the pathophysiology of asthma, such as T helper lymphocyte subsets, and the consequences of various extrinsic and intrinsic factors, and IgE receptor expression-reviewing current concepts in immunotherapeutic approaches for the treatment of this and other allergic diseases. Investigates the only category of treatment showing the potential to affect the natural course of allergic diseases and prevent the onset of asthma. Written by more than 80 internationally renowned pulmonary experts, allergic disease specialists, and basic researchers, Immunotherapy in Asthma discusses the efficacy of new medications examines the role of metachromatic cells, lymphocytes, macrophages, and other cell types present in bronchial biopsies presents basic topics such as the functional and phenotypic properties of Th1 and Th2 cells and their role in allergic disease and the regulation of IgE-mediated inflammatory responses addresses the deleterious effects of smoking and passive exposure to cigarette smoke in children and adults assesses differences and similarities between intrinsic and antigen-induced asthma describes the effects of immunogenic peptides on the cytokine production profile of allergen-specific CD4+ T cells explains the different clinical aspects of allergic responses, such as bronchial hyperreactivity and eosinophilic inflammation of the airways reviews the genetic basis of allergy, as well as risk factors for asthma explores oral, sublingual, local nasal, and local bronchial routes for noninjective immunotherapies evaluates various agents with modulatory effects on normal and pathogenic immune responses focuses on strategies for the prevention of childhood asthma and more! Containing over 3000 references, drawings, and tables, Immunotherapy in Asthma is an indispensable resource for pulmonologists, immunologists, allergists, and medical school students in these disciplines.

Book Asthma  Pathophysiology  Herbal and Modern Therapeutic Interventions

Download or read book Asthma Pathophysiology Herbal and Modern Therapeutic Interventions written by Sheikh Rayees and published by Springer Nature. This book was released on 2021-03-26 with total page 71 pages. Available in PDF, EPUB and Kindle. Book excerpt: Asthma is a chronic airway disease affecting over 300 million people worldwide with an expected increase of an additional 100 million by 2025. Past decade has observed a notable increase in asthma prevalence on both national and global levels with highest rates observed in western countries (about 30%). Over the past 40 years, a drastic increase in global prevalence, morbidity, mortality, and economic burden have been observed due to asthma especially in children. The rising numbers of hospital admissions for asthma, especially young children, reflect an increase in severe asthma, poverty and lack of proper disease management. Worldwide, approximately 180,000 deaths annually are caused due to this condition. The financial burden on a single asthma patient per year in different western countries ranges from US$300–1,300. Asthma is an intricate respiratory disorder with differences in its severity, natural history and hence treatment response. These differences in intensities of various presentations such as bronchial hyper-responsiveness, airway inflammation, mucus production, airflow obstruction make asthma a heterogeneous disease. The mainstay of current therapies for asthma includes inhaled corticosteroids, phosphodiesterase inhibitors, leukotriene modifiers and β2-adrenoceptor agonists. Some of the currently available drugs are efficient in one or more aspects. However the associated side effects or heterogeneity of the disease limit their usefulness and efficacy, thereby putting a demand on development of new drugs and therapies. On the other hand, asthma has also been treated/managed via herbal medications. These approaches have been described in Unani, Ayurvedic or Chinese system of medicine since antiquity. In fact, several anti-asthmatic drugs were developed from herbs commonly utilized in the non-Western system of medicine. This book focuses on the pathophysiology of asthma, its medication (both herbal and modern), limitations and their future prospects.

Book Asthma

    Book Details:
  • Author : Thomas A.E. Platts-Mills
  • Publisher : CRC Press
  • Release : 1999-04-27
  • ISBN : 9781566703734
  • Pages : 260 pages

Download or read book Asthma written by Thomas A.E. Platts-Mills and published by CRC Press. This book was released on 1999-04-27 with total page 260 pages. Available in PDF, EPUB and Kindle. Book excerpt: Asthma is a disease which, beginning in the 1980s, increased in the United States and other countries in both its prevalence and mortality. According to reports by the Center for Disease Control, the number of people with asthma increased by 42% in the last decade, with children, ethnic minorities and the urban poor being most at risk. Timely research on the causes and mechanisms behind the dramatic increase of asthma in the United States and other nations-to epidemic proportions-is presented in this volume. Investigators heading up eight research groups in asthma and/or allergy present their most recent findings, funded by the Center for Indoor Air Research. In addition to the work underway and discussions/suggestions on present research problems, ASTHMA: Causes and Mechanisms of an Epidemic Inflammatory Disease provides a chapter on the causes of asthma-and the reasons for its recent spread, so hotly discussed in the current literature. Researchers in the fields of asthma and allergy, health care providers, and others who follow research in either of these two developing areas will benefit from this book. The book is written at the level of one investigator to another.

Book CRC Desk Reference for Allergy and Asthma

Download or read book CRC Desk Reference for Allergy and Asthma written by Hans-Uwe Simon and published by CRC Press. This book was released on 2000-04-26 with total page 401 pages. Available in PDF, EPUB and Kindle. Book excerpt: As the prevalence of allergic diseases and asthma has increased in recent years, scientists have intensified research efforts to understand the pathogenesis of these sometimes debilitating conditions. Indeed, researchers have provided key insights-and new concepts-that have changed therapeutic strategies. Moreover, allergic inflammation has served

Book Inflammatory Mechanisms in Asthma

Download or read book Inflammatory Mechanisms in Asthma written by Stephen Holgate and published by Routledge. This book was released on 2018-12-07 with total page 1006 pages. Available in PDF, EPUB and Kindle. Book excerpt: This timely volume brings together the latest basic and clinical insights on the cellular and mediator mechanisms involved in the induction and persistence of airway dysfunction of asthma by over 90 experts in the field-paving the way for developing novel and more effective antiinflammatory therapeutic agents and strategies. Furnishing a comprehensive and up-to-date view of the expanding and interrelated components underlying asthma pathogenesis, Inflammatory Mechanisms in Asthma describes how evidence on airway inflammation is obtained with invasive and noninvasive procedures, such as bronchoalveolar lavage and sputum analysis reviews the complex interactions of inflammatory cells that contribute to chronic inflammation and bronchial hyperreactivity, including eosinophils, basophils, neutrophils, fibroblasts, epithelial cells, and macrophages considers mast cells, cytokines, neural factors, leukotrienes, kinins, and other mediators that regulate the development, establishment, or resolution of asthma exacerbations presents new information suggesting that airway changes in asthma can lead to remodeling or airway fibrosis and more! Enhanced with over 4700 references, tables, drawings, and photographs, this compelling investigation into the pathophysiology of asthma is an indispensable resource for pulmonologists, physiologists, immunologists, allergists, epidemiologists, biochemists, molecular biologists, and graduate and medical school students in these disciplines.

Book Indoor Allergens

    Book Details:
  • Author : National Research Council
  • Publisher : National Academies Press
  • Release : 1993-02-01
  • ISBN : 0309048311
  • Pages : 321 pages

Download or read book Indoor Allergens written by National Research Council and published by National Academies Press. This book was released on 1993-02-01 with total page 321 pages. Available in PDF, EPUB and Kindle. Book excerpt: More than 50 million Americans, one out of five, suffer from hay fever, asthma, and other allergic diseases. Many of these conditions are caused by exposure to allergens in indoor environments such as the house, work, and schoolâ€"where we spend as much as 98 percent of our time. Developed by medical, public health, and engineering professionals working together, this unique volume summarizes what is known about indoor allergens, how they affect human health, the magnitude of their effect on various populations, and how they can be controlled. The book addresses controversies, recommends research directions, and suggests how to assist and educate allergy patients, as well as professionals. Indoor Allergens presents a wealth of information about common indoor allergens and their varying effects, from significant hay fever to life-threatening asthma. The volume discusses sources of allergens, from fungi and dust mites to allergenic chemicals, plants, and animals, and examines practical measures for their control. Indoor Allergens discusses how the human airway and immune system respond to inhaled allergens and assesses patient testing methods, covering the importance of the patient's medical history and outlining procedures and approaches to interpretation for skin tests, in vitro diagnostic tests, and tests of patients' pulmonary function. This comprehensive and practical volume will be important to allergists and other health care providers; public health professionals; specialists in building design, construction, and maintenance; faculty and students in public health; and interested allergy patients.

Book Social Networking

    Book Details:
  • Author : Kristin Anne Lambert
  • Publisher :
  • Release : 2019
  • ISBN :
  • Pages : pages

Download or read book Social Networking written by Kristin Anne Lambert and published by . This book was released on 2019 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Asthma is a heterogeneous clinical syndrome that encompasses a remarkably diverse spectrum of chronic lung diseases involving episodic airflow obstruction, bronchial hyperresponsiveness and airway inflammation. Rather than a single disease entity, asthma consists of disease variants or phenotypes that possess divergent immunologic, physiologic, and pathologic features, including varied responses to treatment. One such phenotype, severe asthma, represents a subset of asthmatics who fail to respond to standard therapy with glucocorticoids and remain poorly controlled despite adherence to medication and escalations in clinical management. Representing only 10-15% of asthma, severe asthmatics are a minority of patients who consume a majority of asthma-related healthcare resources and suffer greater morbidity and mortality compared to other asthma subtypes. The exact biologic pathways or endotypes responsible for this vulnerable and difficult-to-treat cluster of patients are still undefined due to the groups overwhelming heterogeneity. We aim to fill this unmet research area through the investigation of inflammatory pathways in severe asthma. Asthma heterogeneity at a population level is the consequence of heterogeneity in cell-to-cell interactions at the molecular level. Assorted cell populations in the lung form diverse networks that collaboratively communicate to initiate and maintain chronic inflammation in various asthma endotypes. Chief among these relationships, airway epithelial cells and T lymphocytes engage in inflammatory dialogue with one another. Their methods for communicating and the content of their messages have not been fully unraveled; although, understanding of these pathways is anticipated to give way to crucial advances in targeted therapeutics for severe, treatment-refractory asthma. In this dissertation, we address the critical need to decipher communications and disentangle intracellular conversations between members of the airway lining and the immune system.Novel cell-to-cell signaling mediators, extracellular vesicles (EVs) have been shown to participate in cellular crosstalk and play roles in immune regulation. We aimed to elucidate the role of extracellular vesicles in severe asthmatic inflammation and hypothesized that EVs would serve as proinflammatory directives from T lymphocytes to airway epithelial cells. Utilizing both peripheral blood mononuclear cells and peripheral CD4+ T lymphocytes of human asthmatics, we studied T-cell derived extracellular vesicle production and function. EVs were produced in response to activating inflammatory stimuli, including dust mite allergen exposure and TCR engagement, and were shed in greater quantities from asthmatic cells compared to healthy controls. Qualitatively, the phenotype of EVs secreted from activated asthmatic T cells mirrored the inflammatory stress of their parental cell and also transmitted the inflammatory phenotype to airway epithelial cells in vitro. EVs upregulated epithelial expression of neutrophilic chemoattractants like CXCL8 (aka IL-8), a pathway associated with severe asthma. Together the data suggest that T-cell derived EVs are generated as a pathogenic swarm of proinflammatory cues capable of altering airway immune function and sustaining chronic inflammation through leukocyte recruitment. More in-depth analysis and profiling of severe asthmatic T cell EVs, uncovered miRNA cargo within extracellular vesicles. Like messages in a bottle, microRNA missives are able to be shuttled between cells, sharing genetic instructions for inflammatory regulation between T lymphocytes and airway epithelium. A proinflammatory miRNA, miR-155 was found in greater abundance within severe asthmatic EVs, while anti-inflammatory molecule and endogenous opponent, miR-146a was found in reduced quantities. The composition of severe asthmatic EVs and the delicate balance between immunoregulatory miRNAs, miR-155 and miR-146a, within EVs likely contributes to the proinflammatory nature of particles and status of inflammation in airway epithelium. We posit that low concentrations of EV-encased miR-146a may result in negligible transfer of anti-inflammatory molecules to airway epithelial cells in severe asthma As a result, we investigated miRNA-based approaches to enhance anti-inflammatory action and boost glucocorticoid functions in airway epithelial cells. We show that overexpression of miR-146a in airway epithelial cells reduces proinflammatory cytokines and when combined with glucocorticoids further suppresses inflammation. This work identifies a novel therapeutic target and innovative approach to overcome steroid resistance in severe asthmatics through exogenous administration of miR-146a. It would be valuable in future studies to investigate exosomal or EV-mediated delivery of miR-146a to airway epithelium. Alternatively, approaches to skew T cell EV cargo towards anti-inflammatory cargo (miR-146a) and away from proinflammatory stowaways (miR-155) may be a worthy line of future investigation to alter EV phenotypes and immune regulation in asthma. In conclusion, our work makes significant strides to characterize novel molecular messages coordinating diverse inflammatory processes in asthma. Our data show that T-cell derived extracellular vesicles and their associated miRNAs participate in cell-to-cell conversations that ultimately coordinate inflammatory responses in the airway. T-cell EVs command inflammatory changes in their target airway cells, inducing neutrophilic chemoattractants required to recruit additional leukocytes to sustain chronic and severe unchecked asthmatic inflammation. Finally, we detect increased numbers of extracellular vesicles and unique extracellular vesicle miRNA signatures for severe asthma. We report that both measures are promising biomarker candidates for the clinical management of severe asthma. Together, these studies elucidate the contributions of extracellular vesicles and miRNAs to a neutrophil-predominant inflammatory endotype associated with severe asthma.

Book Severe Asthma

    Book Details:
  • Author : Kian Fan Chung
  • Publisher : European Respiratory Society
  • Release : 2019-06-01
  • ISBN : 1849841047
  • Pages : 360 pages

Download or read book Severe Asthma written by Kian Fan Chung and published by European Respiratory Society. This book was released on 2019-06-01 with total page 360 pages. Available in PDF, EPUB and Kindle. Book excerpt: Severe asthma is a form of asthma that responds poorly to currently available medication, and its patients represent those with greatest unmet needs. In the last 10 years, substantial progress has been made in terms of understanding some of the mechanisms that drive severe asthma; there have also been concomitant advances in the recognition of specific molecular phenotypes. This ERS Monograph covers all aspects of severe asthma – epidemiology, diagnosis, mechanisms, treatment and management – but has a particular focus on recent understanding of mechanistic heterogeneity based on an analytic approach using various ‘omics platforms applied to clinically well-defined asthma cohorts. How these advances have led to improved management targets is also emphasised. This book brings together the clinical and scientific expertise of those from around the world who are collaborating to solve the problem of severe asthma.

Book T Lymphocytes Subpopulations in Immunotoxicology

Download or read book T Lymphocytes Subpopulations in Immunotoxicology written by Ian Kimber and published by John Wiley & Sons. This book was released on 1998-08-17 with total page 326 pages. Available in PDF, EPUB and Kindle. Book excerpt: Den T-Lymphocyten kommt eine Schlüsselrolle im Immunsystem zu: Sie sind unter anderem für Resistenzen gegenüber Infektionen und Tumoren und für die Entwicklung von Allergien und Autoimmunität verantwortlich. Bisher gab es kein vergleichbares Buch, das Funktionen und Subpopulationen der T-Zellen wie das vorliegende Werk von immunbiologischen Grundlagen ausgehend zusammenfassend darstellt.(05/98)

Book Human Eosinophils

    Book Details:
  • Author : Gianni Marone
  • Publisher : Karger Medical Scientific
  • Release : 2000
  • ISBN : 9783805569743
  • Pages : 0 pages

Download or read book Human Eosinophils written by Gianni Marone and published by Karger Medical Scientific. This book was released on 2000 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Eosinophils represent approximately 1% of peripheral blood leukocytes and play a central proinflammatory and immunoregulatory role in various immune disorders. This volume provides the reader with a comprehensive survey of the major aspects of human eosinophilic biology and immunology as well as the most clinically relevant aspects of eosinophil-related disorders. Expert contributions cover the ultrastructural and phenotypic characteristics of human eosinophils, and their fundamental biochemical features including receptors for IgE and chemokines. The production of cytokines and their role in the activation of eosinophils are reviewed. Furthermore, the classic eosinophil-related disorders such as hypereosinophilia, drug reactions, allergic disorders and some cardiovascular diseases are described. Each of the chapters is written by an investigator actively engaged in research on the topic under consideration. The well-edited and stimulating material compiled in this volume will be of interest to all those working in allergology, immunology, biochemistry and pulmonary medicine.

Book Cytokine Frontiers

    Book Details:
  • Author : Takayuki Yoshimoto
  • Publisher : Springer Science & Business Media
  • Release : 2013-10-28
  • ISBN : 4431544429
  • Pages : 398 pages

Download or read book Cytokine Frontiers written by Takayuki Yoshimoto and published by Springer Science & Business Media. This book was released on 2013-10-28 with total page 398 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book guides the reader through the latest research on the cytokine network, covering signaling pathways, control of the immune response, and potential therapeutics. Different cytokines stimulate diverse responses in various phases of inflammation and immunity, including the innate immune response, the generation of effector T cells, and the development of antibodies by the humoral immune system. It is now clear that the pathophysiology of many infectious, autoimmune, allergic, and malignant diseases can be largely explained by which cytokines are induced and subsequently regulate the cellular responses. In clinical medicine, cytokines are involved in a wide spectrum of diseases. This book describes in three parts the properties and roles of 15 key cytokines under physiological and pathological conditions. Part I presents nine cytokines associated with inflammatory disorders, pro-inflammatory cytokines, and the recently identified new helper T (Th) subset: Th17 cells. Part II gives details of three cytokines associated with allergic disorders, including Th2 responses and recently identified types of innate cells. Part III describes three cytokines that are associated with immunological tolerance and anti-inflammation, including regulatory T (Treg) cells, IL-10-producing Treg (Tr1) cells, and inducible IL-35-producing Treg (iTr35) cells. Cytokines are considered to be important as therapeutic targets for specific agonists or antagonists in numerous immune and inflammatory diseases. The ultimate goal of this book is to facilitate the development of therapeutic treatments for such diseases which has been limited by an insufficient understanding of the biology of cytokines and the complicated network that they create.

Book Regulatory T Cells and Clinical Application

Download or read book Regulatory T Cells and Clinical Application written by Shuiping Jiang and published by Springer Science & Business Media. This book was released on 2008-12-14 with total page 606 pages. Available in PDF, EPUB and Kindle. Book excerpt: Covering one of the hottest topics in immunology today, this book provides a comprehensive view of all types of regulatory T cells described so far in the literature. The book will have broad appeal to both researchers and clinicians.