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 Overview of the Immune System The immune system distinguishes self from nonself and eliminates potentially harmful nonself molecules and cells from the body. The immune system also has the capacity to recognize and destroy... read more .)
Natural Barriers Against Infection
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 Human Papillomavirus (HPV) Infection Human papillomavirus (HPV) infects epithelial cells. Most of the > 100 subtypes infect cutaneous epithelium and cause skin warts; some types infect mucosal epithelium and cause anogenital warts... read more , which can invade normal skin, causing warts
Some parasites (eg, Schistosomiasis Schistosomiasis is infection with blood flukes of the genus Schistosoma, which are acquired transcutaneously by swimming or wading in contaminated freshwater. The organisms infect the... read more , Strongyloides stercoralis Strongyloidiasis Strongyloidiasis is infection with Strongyloides stercoralis. Findings include abdominal pain and diarrhea, rash, pulmonary symptoms (including cough and wheezing), and eosinophilia.... read more , those that cause hookworm infection Hookworm Infection Ancylostomiasis is infection with the hookworm Ancylostoma duodenale or Necator americanus. Symptoms include rash at the site of larval entry and sometimes abdominal pain or other... read more )
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.
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 Cystic Fibrosis Cystic fibrosis is an inherited disease of the exocrine glands affecting primarily the gastrointestinal and respiratory systems. It leads to chronic lung disease, exocrine pancreatic insufficiency... read more ).
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 Shigellosis Shigellosis is an acute infection of the intestine caused by the gram-negative Shigella species. Symptoms include fever, nausea, vomiting, tenesmus, and diarrhea that is usually bloody... read more and Clostridioides difficile–induced colitis Clostridioides (formerly Clostridium) difficile–Induced Diarrhea Toxins produced by Clostridioides difficile strains in the gastrointestinal tract cause pseudomembranous colitis, typically after antibiotic use. Symptoms are diarrhea, sometimes bloody... read more .
Compromised gastrointestinal defense mechanisms may predispose patients to particular infections (eg, achlorhydria predisposes to Salmonella Overview of Salmonella Infections The genus Salmonella is divided into 2 species, S. enterica and S. bongori, which include > 2500 known serotypes. Some of these serotypes are named. In such cases, common... read more , Campylobacter Campylobacter and Related Infections Campylobacter infections typically cause self-limited diarrhea but occasionally cause bacteremia, with consequent endocarditis, osteomyelitis, or septic arthritis. Diagnosis is by culture... read more , and C. difficile Clostridioides (formerly Clostridium) difficile–Induced Diarrhea Toxins produced by Clostridioides difficile strains in the gastrointestinal tract cause pseudomembranous colitis, typically after antibiotic use. Symptoms are diarrhea, sometimes bloody... read more 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 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.
Nonspecific Immune Responses (Innate Immune Responses)
Cytokines Cytokines The immune system consists of cellular components and molecular components that work together to destroy antigens (Ags). (See also Overview of the Immune System.) Acute phase reactants are plasma... read more (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 Polymorphonuclear Leukocytes The immune system consists of cellular components and molecular components that work together to destroy antigens. (See also Overview of the Immune System.) Although some antigens (Ags) can... read more , 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 Chronic Granulomatous Disease (CGD) Chronic granulomatous disease is characterized by white blood cells that cannot produce activated oxygen compounds and by defects in phagocytic cell microbicidal function. Manifestations include... read more ), 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 Antibodies The immune system consists of cellular components and molecular components that work together to destroy antigens (Ags). (See also Overview of the Immune System.) Acute phase reactants are plasma... read more (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 Complement System The complement system is an enzyme cascade that helps defend against infection via activation of a local inflammatory response. Many complement proteins occur in serum as inactive enzyme precursors... read more 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).
Drugs Mentioned In This Article
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