Most gastrointestinal pathogens are transmitted by food or drink contaminated with fecal material. Where hygiene fails, diarrheal disease becomes rampant.
Acidic gastric secretions are important defenses within the gastrointestinal tract and are lethal for many gastrointestinal pathogens. Healthy volunteers do not become infected by Vibrio
cholerae unless they are fed 10 organisms, whereas volunteers given Vibrio cholerae and sodium bicarbonate have a 10,000-fold increase in susceptibility to cholera. In contrast, some
ingested agents, such as Shigella and Giardia cysts, are relatively resistant to gastric acid; hence, as few as 100 organisms of each are sufficient to cause illness.
Other normal defenses within the gastrointestinal tract include (1) the viscous mucous layer covering the gut, (2) lytic pancreatic enzymes and bile detergents, (3) mucosal antimicrobial
peptides called defensins, (4) normal flora, and (5) secreted IgA antibodies. IgA antibodies are made by B cells located in mucosa-associated lymphoid tissues (MALT). These lymphoid
aggregates are covered by a single layer of specialized epithelial cells called M cells. M cells are important for transport of antigens to MALT and for binding and uptake of numerous gut
pathogens, including poliovirus, enteropathic Escherichia coli, Vibrio cholerae, Salmonella typhi, and Shigella flexneri. 
Infections via the gastrointestinal tract occur when local defenses are weakened or the organisms develop strategies to overcome these defenses. Host defenses are weakened by low gastric
acidity, by antibiotics that unbalance the normal bacterial flora (e.g., in pseudomembranous colitis), or when there is stalled peristalsis or mechanical obstruction (e.g., in blind loop
syndrome). Most enveloped viruses are killed by the bile and digestive enzymes, but nonenveloped viruses may be resistant (e.g., the hepatitis A virus, rotaviruses, reoviruses, and Norwalk
Enteropathogenic bacteria elicit gastrointestinal disease by a variety of mechanisms:
• While growing on contaminated food, certain staphylococcal strains release powerful enterotoxins that cause food poisoning symptoms without any bacterial multiplication in the
• V. cholerae and toxigenic E. coli multiply inside the mucous layer overlying the gut epithelium and release exotoxins that cause the gut epithelium to secrete high volumes of
• Shigella, Salmonella, and Campylobacter invade and damage the intestinal mucosa and lamina propria and so cause ulceration, inflammation, and hemorrhage, clinically
manifested as dysentery.
• S. typhi passes from the damaged mucosa through Peyer patches and mesenteric lymph nodes and into the bloodstream, resulting in a systemic infection.
Fungal infection of the gastrointestinal tract occurs mainly in immunologically compromised patients. Candida, part of the normal gastrointestinal flora, shows a predilection for stratified
squamous epithelium, causing oral thrush or membranous esophagitis, but may also disseminate to the stomach, lower gastrointestinal tract, and systemic organs.
The cyst forms of intestinal protozoa are essential for their transmission because cysts resist stomach acid. In the gut, cysts convert to motile trophozoites and attach to sugars on the
intestinal epithelia through surface lectins. Thereafter, there is wide species variation. Giardia lamblia attaches to the epithelial brush border, whereas cryptosporidia are taken up by
enterocytes, in which they form gametes and spores. Entamoeba histolytica causes contact-mediated cytolysis through a channel-forming pore protein and thereby ulcerates and invades the
colonic mucosa. Intestinal helminths, as a rule, cause disease only when they are present in large numbers or in ectopic sites, for example, by obstructing the gut or invading and damaging
the bile ducts (Ascaris lumbricoides). Hookworms may cause iron deficiency anemia by chronic loss of blood sucked from intestinal villi; the fish tapeworm Diphyllobothrium latum can
deplete its host of vitamin B12 , giving rise to an illness resembling pernicious anemia. Finally, the larvae of several helminth parasites pass through the gut briefly on their way toward
another organ habitat; for example, Trichinella spiralis larvae preferentially encyst in muscle, Echinococcus species larvae in the liver or lung.
Some 10,000 microorganisms, including viruses, bacteria, and fungi, are inhaled daily by every city inhabitant. The distance these microorganisms travel into the respiratory system is
inversely proportional to their size. Large microbes are trapped in the mucociliary blanket that lines the nose and the upper respiratory tract. Microorganisms are trapped in the mucus
secreted by goblet cells and are then transported by ciliary action to the back of the throat, where they are swallowed and cleared. Organisms smaller than 5 μm travel directly to the alveoli,
where they are phagocytosed by alveolar macrophages or by neutrophils recruited to the lung by cytokines.
Damage to the mucociliary defense results from repeated insults in smokers and patients with cystic fibrosis, while acute injury occurs in intubated patients and in those who aspirate
gastric acid. Successful respiratory microbes evade the mucociliary defenses in part by attaching to epithelial cells in the lower respiratory tract and pharynx. For example, influenza viruses
possess hemagglutinin proteins that project from the surface of the virus and bind to sialic acid on the surface of epithelial cells. This attachment induces the host cell to engulf the virus,
leading to viral entry and replication within the host cell. However, sialic acid binding prevents newly synthesized viruses from leaving the host cell. Influenza viruses have another cell
surface protein, neuraminidase, which cleaves sialic acid and allows virus to release from the host cell. Neuraminidase also lowers the viscosity of mucus and facilitates viral transit within
the respiratory tract. Interestingly, some anti-influenza drugs are sialic acid analogs that inhibit neuraminidase and prevent viral release from host cells.
Certain respiratory bacterial pathogens can impair ciliary activity. For instance, Haemophilus influenza and Bordetella pertussis elaborate toxins that paralyze mucosal cilia; Pseudomonas
aeruginosa, a cause of severe respiratory infection in persons with cystic fibrosis, and Mycoplasma pneumoniae produce ciliostatic substances. Some bacteria such as Streptococcus
pneumoniae or Staphylococcus species lack specific adherence factors and often gain access after viral infection causes loss of ciliated epithelium, making individuals who have had viral
respiratory infection more susceptible to secondary bacterial respiratory infection. Mycobacterium tuberculosis, in contrast, gains its foothold in normal alveoli because it is able to escape
phagocytic killing by macrophages. Growth requirements for microorganisms can determine their site of infection in the respiratory tract. For example, rhinoviruses, which cause the
common cold, grow optimally at 33°C, the temperature of the nasal mucosa, but grow poorly at 37°C, the temperature of the lower respiratory tract. Finally, opportunistic fungi infect the
lungs when cellular immunity is depressed or when leukocytes are reduced in number (e.g., P. jiroveci [carinii] in AIDS patients and Aspergillus species in chemotherapy patients).
The urinary tract is almost always invaded from the exterior via the urethra. The regular flushing of the urinary tract with urine serves as a defense against invading microorganisms.
Urine in the bladder is normally sterile, and successful pathogens (e.g., gonococci, E. coli) adhere to the urinary epithelium. Anatomy is an important factor for infection. Women have
more than 10 times as many urinary tract infections (UTIs) as men, because the distance between the urinary bladder and skin (i.e., the length of the urethra) is 5 cm, in contrast to 20 cm in
men. Obstruction of urinary flow and/or reflux can compromise normal defenses and increase susceptibility to UTIs. UTIs can spread retrogradely from the bladder to the kidney and cause
acute and chronic pyelonephritis, which is the major preventable cause of renal failure.
From puberty until menopause, the vagina is protected from pathogens by a low pH resulting from catabolism of glycogen in the normal epithelium by lactobacilli. Antibiotics can kill the
lactobacilli and make the vagina susceptible to infection. To be successful as pathogens, microorganisms have developed specific mechanisms for attaching to vaginal or cervical mucosa
or enter via local breaks in the mucosa during sex (genital warts, syphilis).
Date: 2016-04-22; view: 597