E-Book, Englisch, Band 1, 682 Seiten, eBook
Reihe: Molecular Pathology Library
ISBN: 978-0-387-72430-0
Verlag: Springer US
Format: PDF
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Weitere Infos & Material
Basic Concepts of Molecular Pathology.- Genes, Gene Products, and Transcription Factors.- Receptors, Signaling Pathways, Cell Cycle, and DNA Damage Repair.- Cell Adhesion Molecules.- Apoptosis and Cell Death: Relevance to Lung.- Roles of Mutation and Epimutation in the Development of Lung Disease.- Techniques and Experimental Systems in Molecular Pathology.- Bioinformatics and Omics.- General Approach to Molecular Pathology.- Applications of Molecular Tests in Anatomic Pathology.- Polymerase Chain Reaction and Reverse Transcription&###x2014;Polymerase Chain Reaction.- Array Comparative Genomic Hybridization in Pathology.- Loss of Heterozygosity in Lung Diseases.- In Situ Hybridization: Principles and Applications for Pulmonary Medicine.- Proteomics.- Animal Models of Lung Disease.- Tissue Culture Models.- Molecular Pathology of Pulmonary and Pleural Neoplasms: General Principles.- Molecular Oncogenesis of Lung Cancer.- Genetic Susceptibility.- Prognostic Markers.- Pulmonary Angiogenesis in Neoplastic and Nonneoplastic Disorders.- Lung Cancer Stem Cells.- Gene Therapy Approaches for Lung Cancer.- Response to Conventional Therapy and Targeted Molecular Therapy.- Environmental Agents in Lung and Pleural Neoplasms.- Viral Oncogenesis.- Molecular Pathology of Pulmonary and Pleural Neoplasms: Specific Histologic Types.- Adenocarcinoma and Its Precursor Lesions.- Molecular Pathology of Squamous Cell Carcinoma and Its Precursors.- Molecular Pathology of Large Cell Carcinoma and Its Precursors.- Small Cell Carcinoma.- Neuroendocrine Carcinomas and Precursors.- Pulmonary Lymphomas.- Posttransplantation Lymphoproliferative Disorder.- Unusual Benign and Malignant Neoplasms of Lung: Molecular Pathology.- Primary Versus Metastatic Cancer: Gene Expression Profiling.- Diffuse MalignantMesothelioma: Genetic Pathways and Mechanisms of Oncogenesis of Asbestos and Other Agents That Cause Mesotheliomas.- Molecular Pathology of Pediatric Tumors of the Lung.- Molecular Pathology of Pulmonary Infections.- Basis of Susceptibility to Lung Infection.- Molecular Pathology of Viral Respiratory Diseases.- Molecular Pathology of Rickettsial Lung Infections.- Bacteria.- Immunopathology of Tuberculosis.- Molecular Pathology of Fungal Lung Infection.- Parasites.- Molecular Pathology of Other Nonneoplastic Pulmonary Diseases: General Principles.- Inflammation.- Oxidants and Antioxidants.- Epithelial Repair and Regeneration.- Fibrogenesis.- Stem Cells in Nonneoplastic Lung Disorders.- Gene Therapy in Nonneoplastic Lung Disease.- Molecular Pathology of Other Nonneoplastic Pulmonary Diseases: Specific Entities.- Smoking-Related Lung Diseases.- Heritable ?1-Antitrypsin Deficiency.- Asthma.- Cystic Fibrosis.- Pulmonary Organogenesis and Developmental Abnormalities.- Genetic Abnormalities of Surfactant Metabolism.- Usual Interstitial Pneumonia.- Sarcoidosis: Are There Sarcoidosis Genes?.- Histiocytic Diseases of the Lung.- Pulmonary Arterial Hypertension.- Immunopathology of Pulmonary Vasculitides.- Asbestosis and Silicosis.
"Section 5 Molecular Pathology of Pulmonary Infections (p. 369-370)
36 Basis of Susceptibility to Lung Infection
Frank C. Schmalstieg and Armond S. Goldman
Introduction
The myriad microbial pathogens encountered by the lung presents a daunting challenge to the human immune system. Nowhere else in the body is such a vast surface area (approximately 100 m2)1 directly exposed to airborne pathogens at about 20 times per minute. Not only is the area and exposure extreme, but the underlying blood circulation is only two cell layers, of about 0.5 µm each, removed from the alveolar surface. Furthermore, gravity and manifold branching of bronchioles and bronchi interfere with the expulsion of these organisms and tissue debris that occurs during lung infection. It is not surprising, then, that pneumonias are among the most common infectious diseases in the United States.
Understanding the susceptibility to lung infection requires a comprehension of (1) the anatomy and function of the lung, (2) environmental exposures, (3) systemic and mucosal immune functions, (4) virulence of pathogens, and (5) genetic variabilities of the host defenses. Numerous “experiments of nature” and identi- ? cation of the molecular mechanisms of pathogen entry into lung cells especially have provided unique insights into understanding immune aspects of host susceptibility. More recently, rapid, high volume methods of analyzing potential genetic determinants for host susceptibility to speci? c pathogens have shown considerable promise. These considerations and their results are explored in some detail in this chapter.
Lung Anatomy and Function
Unique Aspects of the Lung Microcirculation
Three distinct circulations supply the lung and airways with blood. They are the tracheal, bronchial, and pulmonary circulations. The tracheal arteries branch from the superior and inferior thyroid arteries and drain to the inferior thyroid venous plexus. More importantly, the bronchial arterial supply is from the thoracic aorta, and the venous drainage from this artery is largely (~70%) anastomosed to the pulmonary circulation in a precapillary location3 in the sheep. This also likely occurs in humans.
These anastomoses are signi? cant because neutrophils may be in? uenced by mediators from airway epithelium and then interact directly with the pulmonary capillaries, thus providing a connection with in? ammation in the airway and in the alveolar capillaries. In this regard, the capillary diameter in the bronchial microcirculation is about 8.5 µm but only approximately 5.5 µm in the pulmonary capillaries.4 Neutrophils have to deform during passage through the pulmonary capillaries (Figure 36.1) because of their relatively large diameter (10– 15 µm).
In contrast, erythrocytes pass through those capillaries more readily because of their smaller diameters. Delay in the passage of neutrophils results in a relative increase in neutrophil concentration in the pulmonary capillaries.5 This may be an adaptive modi? cation for better control of any organisms breaching the extensive and exposed surfaces of the alveoli.
The slowing and momentary stopping of neutrophils in the pulmonary capillaries under certain stimuli may allow selectin- and integrin-independent migration of these cells from the capillaries.6,7 The bronchial circulation is also unique in that airway injury can stimulate a ? vefold increase in bronchial blood ? ow in sheep.
Although the increased blood ? ow during injury amounts to less than 3% of the cardiac output, neutrophils activated in the bronchial microcirculation may be directly delivered to the pulmonary capillaries to produce damage. In fact, bronchial artery ligation decreases lung edema in a sheep model of smoke and burn injury.9 The anatomy of the lung then potentially allows damage in the airway to produce in? ammatory changes in the lung that may enhance lung protection or lead to further damage under some circumstances."
