The Immunological Basis of Asthma
http://www.100md.com
《新英格兰医药杂志》
Asthma and its immunopathophysiology are subjects that prompt many questions. How important are inhaled allergens to sensitization and provocation? What is the role of inflammatory cells, such as eosinophils, lymphocytes, mast cells, and basophils? Does asthma that is apparently not triggered by exposure to allergens (intrinsic or idiopathic asthma) differ in its pathophysiological characteristics from allergic (extrinsic) asthma? What is the mechanism by which aspirin causes violent asthmatic reactions in patients who have asthma that is complicated by the presence of nasal polyps and blood eosinophilia? What is the relation between the occurrence of nasal polyps and asthma? Why is the prevalence of asthma increasing, and what might we do about it? What are the most important targets for therapeutic intervention? These are but a few of the questions that come to mind.
This multiauthored, comprehensive review of the immunology of asthma deals with many of these questions and illuminates an increasingly complex subject. The editors, who are based in the Netherlands, have selected authoritative, predominantly European contributors for the 24 chapters. The presentation is divided into four parts. The first part, consisting of seven chapters, concentrates on cells of the pulmonary immune system and covers the functions of antigen-presenting cells; B-cells and their differentiation; IgE synthesis; inflammatory cells, including mast cells, basophils, and eosinophils; and airway epithelium. Although this part is informative and crucial to understanding subsequent chapters, at times it becomes difficult reading. For example, even though abbreviations reduce the volume of text and speed communication in some areas, they can also become obstacles. Many of the authors would have aided their cause by providing a list of abbreviations to sustain the reader. (Readers, take my advice and create your own list of abbreviations for reference as you go through the first part of this book — a list will help keep you from falling prey to a stupor due to polyalphanumeracy.)
The second part of the book, consisting of six chapters on the regulation of the pulmonary immune response, discusses the effects of inhaled antigen and its ability to cause tolerance and the sensitization and provocation of immune responses, including the importance of dendritic cells and pattern-recognition receptors to the polarization of T-helper responses. The CD28 and B7 superfamily members, critical for T-cell costimulation and regulation, are identified, and current information is reviewed; this topic is especially relevant in view of recent reports on new therapies that target T-cell costimulation. Physicians caring for patients with asthma understand the importance of the effect of emotions and stress on these patients, and the chapter on the relation between the immune and neurologic systems identifies and evaluates this interaction.
The third part, consisting of seven chapters on the integrated immunology of airway inflammation, is focused specifically on asthma and the consequences of sensitization in asthma. In an especially well done chapter on eosinophilic airway inflammation in animal models, the authors scrutinize the often confusing and sometimes contradictory findings from the murine model of asthma and highlight the key messages in these studies. The chapter on atopic and nonatopic asthma tells us that the pattern of cytokine expression does not differ substantially in allergic and nonallergic asthma, in spite of the feeble IgE antibody formation in nonatopic asthma. The question of why serum levels of IgE are near normal in the face of severe asthma remains unanswered; the possibility of a local IgE response remains enigmatic. Regrettably, the authors do not grapple with the problem of idiosyncratic reactions to aspirin and their relation to nasal polyposis and sinusitis and the underlying immunopathologic features of the disease.
Last, the four chapters in the fourth part of the book deal with current and proposed therapies for asthma and the relative paucity of new therapies. The authors point to the increased prevalence of asthma and discuss "the hygiene hypothesis." How one might purposefully substitute bacterial products (rather than bacterial infections) to switch the immune response from a type 2 to a type 1 helper T-cell response is explored, and the potentially favorable outcomes and problems of such approaches are discussed in detail. The final chapter discusses the use of adenovirus-mediated gene therapies and how these might be used to modify asthma.
The concept that asthma has an immunologic basis presupposes the existence of an immune response and, presumably, of an allergen to which the response occurs. However, frequently it is difficult to identify allergens that provoke asthma, and indeed, many physicians treat asthma as idiopathic eosinophilic bronchial inflammation. We know that viral infections and neurogenic stimulation may alter inflammation, and parts of the book are devoted to this topic. The antigen-dependent murine model has been extensively investigated, and this work has led to extensive new information. Although this model is informative in instructing us about the mechanisms of the lung's response to an antigen, however, the information it has provided may be less important for our understanding of asthma as we see it in the clinic.
In spite of these caveats, this book provides a solid foundation of knowledge related to the immunology of the lung. It is a necessary source for investigators and clinicians grappling with understanding the mechanisms of asthma. Moreover, the extensive and thorough discussion of both pulmonary immune responses and asthma makes the textbook valuable to allergists and pulmonologists alike.
Gerald J. Gleich, M.D.
University of Utah
Salt Lake City, UT 84132-2409
gerald.gleich@hsc.utah.edu((Lung Biology in Health a)
This multiauthored, comprehensive review of the immunology of asthma deals with many of these questions and illuminates an increasingly complex subject. The editors, who are based in the Netherlands, have selected authoritative, predominantly European contributors for the 24 chapters. The presentation is divided into four parts. The first part, consisting of seven chapters, concentrates on cells of the pulmonary immune system and covers the functions of antigen-presenting cells; B-cells and their differentiation; IgE synthesis; inflammatory cells, including mast cells, basophils, and eosinophils; and airway epithelium. Although this part is informative and crucial to understanding subsequent chapters, at times it becomes difficult reading. For example, even though abbreviations reduce the volume of text and speed communication in some areas, they can also become obstacles. Many of the authors would have aided their cause by providing a list of abbreviations to sustain the reader. (Readers, take my advice and create your own list of abbreviations for reference as you go through the first part of this book — a list will help keep you from falling prey to a stupor due to polyalphanumeracy.)
The second part of the book, consisting of six chapters on the regulation of the pulmonary immune response, discusses the effects of inhaled antigen and its ability to cause tolerance and the sensitization and provocation of immune responses, including the importance of dendritic cells and pattern-recognition receptors to the polarization of T-helper responses. The CD28 and B7 superfamily members, critical for T-cell costimulation and regulation, are identified, and current information is reviewed; this topic is especially relevant in view of recent reports on new therapies that target T-cell costimulation. Physicians caring for patients with asthma understand the importance of the effect of emotions and stress on these patients, and the chapter on the relation between the immune and neurologic systems identifies and evaluates this interaction.
The third part, consisting of seven chapters on the integrated immunology of airway inflammation, is focused specifically on asthma and the consequences of sensitization in asthma. In an especially well done chapter on eosinophilic airway inflammation in animal models, the authors scrutinize the often confusing and sometimes contradictory findings from the murine model of asthma and highlight the key messages in these studies. The chapter on atopic and nonatopic asthma tells us that the pattern of cytokine expression does not differ substantially in allergic and nonallergic asthma, in spite of the feeble IgE antibody formation in nonatopic asthma. The question of why serum levels of IgE are near normal in the face of severe asthma remains unanswered; the possibility of a local IgE response remains enigmatic. Regrettably, the authors do not grapple with the problem of idiosyncratic reactions to aspirin and their relation to nasal polyposis and sinusitis and the underlying immunopathologic features of the disease.
Last, the four chapters in the fourth part of the book deal with current and proposed therapies for asthma and the relative paucity of new therapies. The authors point to the increased prevalence of asthma and discuss "the hygiene hypothesis." How one might purposefully substitute bacterial products (rather than bacterial infections) to switch the immune response from a type 2 to a type 1 helper T-cell response is explored, and the potentially favorable outcomes and problems of such approaches are discussed in detail. The final chapter discusses the use of adenovirus-mediated gene therapies and how these might be used to modify asthma.
The concept that asthma has an immunologic basis presupposes the existence of an immune response and, presumably, of an allergen to which the response occurs. However, frequently it is difficult to identify allergens that provoke asthma, and indeed, many physicians treat asthma as idiopathic eosinophilic bronchial inflammation. We know that viral infections and neurogenic stimulation may alter inflammation, and parts of the book are devoted to this topic. The antigen-dependent murine model has been extensively investigated, and this work has led to extensive new information. Although this model is informative in instructing us about the mechanisms of the lung's response to an antigen, however, the information it has provided may be less important for our understanding of asthma as we see it in the clinic.
In spite of these caveats, this book provides a solid foundation of knowledge related to the immunology of the lung. It is a necessary source for investigators and clinicians grappling with understanding the mechanisms of asthma. Moreover, the extensive and thorough discussion of both pulmonary immune responses and asthma makes the textbook valuable to allergists and pulmonologists alike.
Gerald J. Gleich, M.D.
University of Utah
Salt Lake City, UT 84132-2409
gerald.gleich@hsc.utah.edu((Lung Biology in Health a)