Reynolds H Y
Pulmonary Section, Yale University School of Medicine, New Haven, Connecticut.
Clin Chest Med. 1987 Sep;8(3):339-58.
Host defense mechanisms spaced along the respiratory tree and in the alveolar spaces effectively remove or contend with micro-organisms that enter the airways, so serious lung infections occur rarely in healthy people. Special circumstances, such as virgin exposure to a virulent microbe or a large innoculum of a pathogen, can result in illness, but usually routine surveillance host defenses are protective and suffice to keep colonizing airway flora in check. When pneumonia develops or recurrent sinopulmonary infection exists, however, some element of the normal defense apparatus may have failed or is inadequate. This review highlights several components of the apparatus, that is immunoglobulins IgG and IgA and the interaction of alveolar macrophages and lymphocytes, and examines deficiencies in their function that may result in infection. Along the conducting airways, poor mucociliary clearance and/or deficiencies in certain IgG subclass antibodies or destruction of IgA may predispose to sinopulmonary infections; these may be a manifestation of a hereditary disease. In pneumonia the alveolar macrophage is positioned as the central cell which must respond in several directions. This scavenger phagocyte first intercepts the microbe and either can kill or contain it or must call in some other phagocytic cell or inflammatory mediator(s) for assistance. Opsonic antibodies (IgG) and other nonimmune opsonins (complement and surfactant or fibronectin fragments) facilitate phagocytosis, but an absence of antibody may permit infection to develop with encapsulated bacteria (pneumococcus). Insufficient bone marrow reserves of PMNs or a paucity of chemotactic factors to attract them into the alveoli is a situation that may permit gram-negative bacilli and fungal organisms to flourish. Inability of immune T-lymphocytes to energize macrophages, through soluble cellular mediators that provide cell-mediated immunity and activation, makes containment of certain intracellular microbes impossible for these phagocytes (Legionella or mycobacteria). Likewise, concomitant infection of macrophages with viruses (human immunodeficiency virus, and cytomegalovirus or herpes viruses) plus an excessive T-lymphocyte suppressor cell influence may make P. carinii and common bacterial and fungal organisms difficult to contain in the lungs of AIDS patients. Consideration about what the lung host deficiency might be can make therapy more specific through immunization to develop special antibodies, replacement of certain immunoglobulins (IgG subclasses), or selective administration of cell mediators (gamma-interferon or interleukins).
沿呼吸道树和肺泡腔分布的宿主防御机制能有效清除或抵御进入气道的微生物,因此健康人很少发生严重肺部感染。特殊情况,如初次接触强毒微生物或大量病原体接种,可能导致发病,但通常常规监测的宿主防御机制具有保护作用,足以控制气道定植菌群。然而,当发生肺炎或反复出现鼻窦肺部感染时,正常防御机制的某些环节可能已经失效或不足。本综述重点介绍了该防御机制的几个组成部分,即免疫球蛋白IgG和IgA以及肺泡巨噬细胞与淋巴细胞的相互作用,并探讨了其功能缺陷可能导致感染的情况。在传导气道中,黏液纤毛清除功能不良和/或某些IgG亚类抗体缺乏或IgA破坏可能易患鼻窦肺部感染;这些可能是遗传性疾病的表现。在肺炎中,肺泡巨噬细胞是关键细胞,必须在多个方面发挥作用。这种吞噬性清道夫细胞首先拦截微生物,要么杀死或抑制它,要么必须召唤其他吞噬细胞或炎症介质来提供帮助。调理素抗体(IgG)和其他非免疫调理素(补体、表面活性剂或纤连蛋白片段)促进吞噬作用,但缺乏抗体可能使有荚膜细菌(肺炎球菌)引发感染。中性粒细胞骨髓储备不足或缺乏趋化因子将它们吸引到肺泡中,可能使革兰氏阴性杆菌和真菌大量繁殖。免疫T淋巴细胞无法通过提供细胞介导免疫和激活的可溶性细胞介质来激活巨噬细胞,使得这些吞噬细胞无法控制某些细胞内微生物(军团菌或分枝杆菌)。同样,巨噬细胞同时感染病毒(人类免疫缺陷病毒、巨细胞病毒或疱疹病毒)以及过度的T淋巴细胞抑制细胞影响,可能使卡氏肺孢子虫以及常见细菌和真菌在艾滋病患者肺部难以控制。考虑肺部宿主可能存在的缺陷,通过免疫接种产生特殊抗体、补充某些免疫球蛋白(IgG亚类)或选择性给予细胞介质(γ干扰素或白细胞介素),可以使治疗更具针对性。