Mechanisms of bacterial clearance

The development of pneumonia depends on interaction between bacterial innoculum size and local lung defenses. These may be altered by the underlying disease, comorbidities, malnutrition, and some therapies. Mechanical defenses prevent micro-organisms from entering the lower airway tract. If these defenses are bypassed in the normal host, viable organisms are eradicated from the lower respiratory tract by a very efficient and rapid process in which killing of micro-organisms by phagocytes is of great importance. However, uncontrolled infection may develop in the presence of highly virulent organisms, large microbial inoculums, or failure of cellular defenses to restrict microbial replication. In the normal host, local and systemic defenses can be further amplified by activation of an immune response mediated by cytokines that limits microbial invasion but may cause serious abnormalities in the lung or other organs.

Mechanical defenses

Mechanical defenses include filtration and humidification of inspired air in the upper airways, intact epiglottic and cough reflexes, tracheobronchial secretions, and mucociliary transport. Cigarette smoke alters both the ciliated epithelium and macrophage activity.

The presence of an endotracheal tube produces mucociliary dysfunction and a less effective cough. If mucociliary clearance is slow, respiratory tract mucus traps bacteria which, instead of being removed, proliferate and lead to both colonization and infection. In addition, if there is excessive mucus secretion, the bacterial receptors in secretions may promote colonization by providing organisms with more loci to bind within the airway.

Cellular defenses

Cell-mediated immunity is modulated by alveolar macrophages, T lymphocytes, and polymorphonuclear neutrophils. Alveolar macrophages account for 85 per cent of the total cellularity of the alveoli and are the most important defensive system against microbes in the lung. Macrophages interact with bacteria through the binding of molecules to specific membrane surface receptors.

The most important process during phagocytosis is oxidative burst. Non-oxidative mechanisms include the release of enzymes such as proteases, hydrolases, and lysozymes. Lymphocytes form 10 per cent of the alveolar cell population and produce soluble mediators that stimulate alveolar macrophages. This mechanism seems to be regulated by cytokines. In addition, alveolar macrophages are able to release several mediators (e.g. interleukin 8, C5a, leukotriene B4, and platelet activating factor) with potent chemotactic activity for polymorphonuclear bodies. These cells act mainly through phagocytosis and exert their antibacterial activity in a dose-dependent manner via the release of granular enzymes. They constitude the primary defense against pathogens such as Staphylococcus aureus or fungi. Finally, natural killer cells are lymphocytes responsible for immunological surveillance of viral infections.

Humoral immunity

B lymphocytes, immunoglobulins, and complement constitute the key points of humoral immunity. Structures on the microbial surface, such as endotoxin and certain carbohydrate domains, can activate complement components through the alternate pathway. In immune hosts, binding of specific immunoglobulin G or M molecules to the microbial surface initiates activation of the classical pathway. Both pathways of complement activation result in binding of C3b to the infectious agent, which can be recognized by the type 1 complement receptors on neutrophils and macrophages. In addition, local secretory immunoglobulin A promotes clumping and decreases the adherence of a variety of bacteria to the airway. It also protects the lung against certain viruses, and deficit of this substance predisposes to recurrent episodes.

Healthy Fat Loss For A Longer Life

Healthy Fat Loss For A Longer Life

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