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Host Defense Mechanisms Against Infection
Host defenses that protect against infection include natural barriers (eg, skin, mucous membranes), nonspecific immune responses (eg, phagocytic cells [neutrophils, macrophages] and their products), and specific immune responses (eg, antibodies, lymphocytes).
Many mucous membranes are bathed in secretions that have antimicrobial properties (eg, cervical mucus, prostatic fluid, and tears containing lysozyme, which splits the muramic acid linkage in bacterial cell walls, especially in gram-positive organisms). Local secretions also contain immunoglobulins, principally IgG and secretory IgA, which prevent microorganisms from attaching to host cells.
The respiratory tract has upper airway filters. If invading organisms reach the tracheobronchial tree, the mucociliary epithelium transports them away from the lung. Coughing also helps remove organisms. If the organisms reach the alveoli, alveolar macrophages and tissue histiocytes engulf them. However, these defenses can be overcome by large numbers of organisms or by compromised effectiveness resulting from air pollutants (eg, cigarette smoke) or interference with protective mechanisms (eg, endotracheal intubation, tracheostomy).
GI tract barriers include the acid pH of the stomach and the antibacterial activity of pancreatic enzymes, bile, and intestinal secretions. Peristalsis and the normal loss of epithelial cells remove microorganisms. If peristalsis is slowed (eg, because of drugs such as belladonna or opium alkaloids), this removal is delayed and prolongs some infections, such as symptomatic shigellosis. Compromised GI defense mechanisms may predispose patients to particular infections (eg, achlorhydria predisposes to salmonellosis). Normal bowel flora can inhibit pathogens; alteration of this flora with antibiotics can allow overgrowth of inherently pathogenic microorganisms (eg, Salmonella typhimurium) or superinfection with ordinarily commensal organisms (eg, Candida albicans).
GU tract barriers include the length of the urethra (20 cm) in men, the acid pH of the vagina in women, and the hypertonic state of the kidney medulla. The kidneys also produce and excrete large amounts of Tamm-Horsfall mucoprotein, which binds certain bacteria, facilitating their harmless excretion.
Cytokines (including IL-1, IL-6, tumor necrosis factor-α, interferon-γ) are produced principally by macrophages and activated lymphocytes and mediate an acute-phase response that develops regardless of the inciting microorganism (see also Components of the Immune System : Cytokines). The response involves fever and increased production of neutrophils by the bone marrow. Endothelial cells also produce large amounts of IL-8, which attracts neutrophils.
The inflammatory response directs immune system components to injury or infection sites and is manifested by increased blood supply and vascular permeability, which allows chemotactic peptides, neutrophils, and mononuclear cells to leave the intravascular compartment. Microbial spread is limited by engulfment of microorganisms by phagocytes (eg, neutrophils, macrophages). Phagocytes are drawn to microbes via chemotaxis and engulf them, releasing phagocytic lysosomal contents that help destroy microbes. Oxidative products such as hydrogen peroxide are generated by the phagocytes and kill ingested microbes. When quantitative or qualitative defects in neutrophils result in infection, the infection is usually prolonged and recurrent and responds slowly to antimicrobial drugs. Staphylococci, gram-negative organisms, and fungi are the pathogens usually responsible.
After infection, the host can produce a variety of antibodies (complex glycoproteins known as immunoglobulins) that bind to specific microbial antigenic targets. Antibodies can help eradicate the infecting organism by attracting the host’s WBCs and activating the complement system. The complement system (see page Complement System) destroys cell walls of infecting organisms, usually through the classical pathway. Complement can also be activated on the surface of some microorganisms via the alternative pathway. Antibodies can also promote the deposition of substances known as opsonins (eg, the complement protein C3b) on the surface of microorganisms, which helps promote phagocytosis. Opsonization is important for eradication of encapsulated organisms such as pneumococci and meningococci.
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