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).

Natural Barriers
Skin: The skin usually bars invading microorganisms unless it is physically disrupted (eg, by injury, ! catheter, or surgical incision). "#ceptions include human papillomavirus, $hich can invade normal skin, causing $arts, and some parasites (eg, Schistosoma mansoni,Strongyloides stercoralis). Mucous membranes: %any mucous membranes are bathed in secretions that have antimicrobial properties (eg, cervical mucus, prostatic fluid, and tears containing lyso&yme, $hich splits the muramic acid linkage in bacterial cell $alls, especially in gram'positive organisms). (ocal secretions also contain immunoglobulins, principally g) and secretory g*, $hich prevent microorganisms from attaching to host cells. Respiratory tract: The respiratory tract has upper air$ay filters. f invading organisms reach the tracheobronchial tree, the mucociliary epithelium transports them a$ay from the lung. +oughing also helps remove organisms. f the organisms reach the alveoli, alveolar macrophages and tissue histiocytes engulf them. Ho$ever, these defenses can be overcome by large numbers of organisms or by compromised effectiveness resulting from air pollutants (eg, cigarette smoke) or interference $ith protective mechanisms (eg, endotracheal intubation, tracheostomy). GI tract: ) tract barriers include the acid pH of the stomach and the antibacterial activity of pancreatic en&ymes, bile, and intestinal secretions. ,eristalsis and the normal loss of epithelial cells remove microorganisms. f peristalsis is slo$ed (eg, because of drugs such as belladonna or opium alkaloids), this removal is delayed and prolongs some infections, such as symptomatic shigellosis. +ompromised ) defense mechanisms may predispose patients to particular infections (eg, achlorhydria predisposes to salmonellosis). -ormal bo$el flora can inhibit pathogens. alteration of this flora $ith antibiotics can allo$ overgro$th of inherently pathogenic microorganisms (eg, Salmonella typhimurium) or superinfection $ith ordinarily commensal organisms (eg, Candida albicans). GU tract: )/ tract barriers include the length of the urethra (01 cm) in men, the acid pH of the vagina in $omen, and the hypertonic state of the kidney medulla. The kidneys also produce and e#crete large amounts of Tamm'Horsfall mucoprotein, $hich binds certain bacteria, facilitating their harmless e#cretion.

Nonspecific Immune Responses

+ytokines (including ('2, ('3, tumor necrosis factor'4, interferon'5) are produced principally by macrophages and activated lymphocytes and mediate an acute'phase response that develops regardless of the inciting microorganism (see also 6iology of the mmune 7ystem8 +ytokines). The response involves fever and increased production of neutrophils by the bone marro$. "ndothelial cells also produce large amounts of ('9, $hich attracts neutrophils.

The inflammatory response directs immune system components to injury or infection sites and is manifested by increased blood supply and vascular permeability, $hich allo$s chemotactic peptides, neutrophils, and mononuclear cells to leave the intravascular compartment. %icrobial spread is limited by engulfment of microorganisms by phagocytes (eg, neutrophils, macrophages). ,hagocytes are dra$n to microbes via chemota#is and engulf them, releasing phagocytic lysosomal contents that help destroy microbes. :#idative products such as hydrogen pero#ide are generated by the phagocytes and kill ingested microbes. ;hen <uantitative or <ualitative defects in neutrophils result in infection, the infection is usually prolonged and recurrent and responds slo$ly to antimicrobial drugs. 7taphylococci, gram'negative organisms, and fungi are the pathogens usually responsible.

Specific Immune Responses

*fter infection, the host can produce a variety of antibodies (comple# glycoproteins kno$n as immunoglobulins) that bind to specific microbial antigenic targets. *ntibodies can help eradicate the infecting organism by attracting the host=s ;6+s and activating the complement system. The complement system (see 6iology of the mmune 7ystem8 +omplement 7ystem) destroys cell $alls of infecting organisms, usually through the classical path$ay. +omplement can also be activated on the surface of some microorganisms via the alternative path$ay. *ntibodies can also promote the deposition of substances kno$n as opsonins (eg, the complement protein +>b) on the surface of microorganisms, $hich helps promote phagocytosis. :psoni&ation is important for eradication of encapsulated organisms such as pneumococci and meningococci.