Host Defense Mechanisms Against Infection
Host defenses that protect against infection include
(See also Overview of the Immune System.)
The skin usually bars invading microorganisms unless it is physically disrupted (eg, by arthropod vectors, injury, IV catheters, surgical incision). Exceptions include the following:
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, and proteins that bind iron, which is essential for many microorganisms.
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, by compromised effectiveness resulting from air pollutants (eg, cigarette smoke), interference with protective mechanisms (eg, endotracheal intubation, tracheostomy), or by inborn defects (eg, cystic fibrosis).
Gastrointestinal 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 intestinal 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 and Clostridioides difficile–induced colitis.
Normal bowel flora can inhibit pathogens; alteration of this flora with antibiotics can allow overgrowth of inherently pathogenic microorganisms (eg, Salmonella Typhimurium), overgrowth and toxin formation of C. difficile, or superinfection with ordinarily commensal organisms (eg, Candida albicans).
Genitourinary tract barriers include the length of the urethra (20 cm) in men, the acid pH of the vagina in women, the hypertonic state of the kidney medulla, and the urine urea concentration.
The kidneys also produce and excrete large amounts of Tamm-Horsfall mucoprotein, which binds certain bacteria, facilitating their harmless removal.
Cytokines (including interleukins 1 and 6, tumor necrosis factor-alpha, and interferon-gamma) are produced principally by macrophages and activated lymphocytes and mediate an acute-phase response that develops regardless of the inciting microorganism. The response involves fever and increased production of neutrophils by the bone marrow. Endothelial cells also produce large amounts of interleukin-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 (eg, chronic granulomatous disease), 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 white blood cells and activating the complement system.
The 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.
For many pathogens, the host's genetic make-up influences the host's susceptibility and the resulting morbidity and mortality. For example, patients who have deficiencies of the terminal complement components (C5 through C8, perhaps C9) have an increased susceptibility to infections caused by neisserial species.