Host defenses that protect against infection include
Natural barriers (eg, skin, mucous membranes)
Nonspecific immune responses (eg, phagocytic cells [neutrophils, macrophages] and their products)
Specific immune responses (eg, antibodies, lymphocytes)
(See also Overview of the Immune System.)
Natural Barriers Against Infection
Skin
The skin usually bars invading microorganisms unless it is physically disrupted (eg, by arthropod vectors, injury, IV catheters, surgical incision). Exceptions include the following:
Human papillomavirus, which can invade normal skin, causing warts
Some parasites (eg, , Strongyloides stercoralis, those that cause hookworm infection)
Mucous membranes
Many mucous membranes are bathed in secretions that have antimicrobial properties. For example, cervical mucus, prostatic fluid, and tears contain lysozyme, which splits the muramic acid linkage in bacterial cell walls, especially in gram-positive organisms; gram-negative bacteria are protected by lipopolysaccharides in their outer membrane.
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.
Respiratory tract
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
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.
Compromised gastrointestinal defense mechanisms may predispose patients to particular infections (eg, achlorhydria predisposes to Salmonella, Campylobacter, and C. difficile infections).
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
The kidneys also produce and excrete large amounts of Tamm-Horsfall mucoprotein, which binds certain bacteria, facilitating their harmless removal.
Nonspecific Immune Responses (Innate Immune Responses)
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, neutrophilschronic 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.
Specific Immune Responses (Adaptive Immune Responses)
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.
Host Genetic Factors
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 (eg, meningococcus, gonococcus).
