Porth's Essentials of Pathophysiology, 4e

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Infection and Immunity

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TABLE 14-2 Examples of Virulence Factors Produced by Pathogenic Microorganisms Factor Category Organism Effect on Host

Cholera toxin

Exotoxin Exotoxin

Vibrio cholerae (bacterium)

Secretory diarrhea

Diphtheria toxin

Corynebacterium diphtheriae (bacterium)

Inhibits protein synthesis Fever, hypotension, shock

Lipopolysaccharide Endotoxin Many gram-negative bacteria

Toxic shock toxin Hemagglutinin

Enterotoxin Staphylococcus aureus (bacterium)

Rash, diarrhea, vomiting, hepatitis

Adherence Influenza virus

Establishment of infection Establishment of infection

Pili

Adherence Neisseria gonorrhoeae (bacterium)

Leukocidin IgA protease

Evasive Evasive Evasive Invasive Invasive Invasive Exotoxin Exotoxin

S. aureus

Kills phagocytes

Haemophilus influenzae (bacterium) Cryptococcus neoformans (yeast) Pseudomonas aeruginosa (bacterium) Clostridium perfringens (bacterium) Clostridium botulinum (bacterium) Streptococcus pneumoniae (bacterium) Aspergillus (mold)

Inactivates antibody Prevents phagocytosis Penetration of tissue Penetration of tissue Penetration of tissue

Capsule

Collagenase

Protease

Phospholipase Botulinum toxin

Neuroparalysis, inhibits acetylcholine release

Pneumolysin

Inhibition of respiratory ciliated and phagocytic cell function

Exotoxins are proteins released from the bacterial cell during growth. Bacterial exotoxins enzymatically inactivate or modify key aspects of host cell struc- ture or function, leading to cell death or dysfunc- tion. Diphtheria toxin, for example, inhibits protein synthesis; botulism toxin decreases the release of neurotransmitter from cholinergic neurons, causing flaccid paralysis; tetanus toxin decreases the release of neurotransmitter from inhibitory neurons, producing spastic paralysis; and cholera toxin induces fluid secre- tion into the lumen of the intestine, causing diarrhea. Bacterial exotoxins that produce vomiting and diar- rhea are sometimes referred to as enterotoxins. There has been resurgent interest in streptococcal pyrogenic exotoxin A (SPEA), an exotoxin produced by certain strains of group A, β -hemolytic streptococci ( S. pyo- genes ) that causes a life-threatening toxic shock–like syndrome. The syndrome, sometimes called Henson disease because this infection caused the death of famous puppeteer Jim Henson, is typified by inva- sion of the skin and soft tissues, acute respiratory dis- tress syndrome, and renal failure. Other enterotoxins that have gained notoriety include the Shiga toxins produced by Escherichia coli O157:H7 (see Chapter 29). The ingestion of undercooked hamburger meat or unpasteurized fruit juices contaminated with this organism produces hemorrhagic colitis and a some- times fatal illness called hemolytic uremic syndrome (HUS), characterized by vascular endothelial damage, acute renal failure, and thrombocytopenia. Hemolytic uremic syndrome occurs primarily in infants and young children who have not developed antibodies to the Shiga toxins. Adhesion Factors No interaction between microorganisms and humans can progress to infection or disease if the pathogen is unable to attach to and colonize the host. The process of microbial attachment may be site specific

(e.g., mucous membranes, skin surfaces), cell specific (e.g., T lymphocytes, respiratory epithelium, intestinal epithelium), or nonspecific (e.g., moist areas, charged surfaces). In any of these cases, adhesion requires a posi- tive interaction between the surfaces of host cells and the infectious agent. After initial attachment, some bacterial agents become embedded in a gelatinous matrix of polysaccha- rides called a slime (or mucous) layer. The slime layer serves two purposes: it anchors the agent firmly to host tissue surfaces and it protects the agent from the immu- nologic defenses of the host. Many viral agents, including influenza, mumps, mea- sles, and adenovirus, produce hair-like appendages or spikes called fimbriae. Fimbriae are used by bacteria to attach to one another or attach to cell surfaces. On the distal tips of fimbriae, hemagglutinins recognize carbo- hydrate receptors on the surfaces of specific cells in the host, allowing the bacteria to attach to the host cell in a specific manner. Evasion Factors A number of factors produced by microorganisms enhance virulence by evading various components of the host’s immune system. Extracellular polysaccha- rides, including capsules, slime, and mucous layers, discourage engulfment and killing of pathogens by the host’s phagocytic white blood cells (i.e., neutrophils and macrophages). Encapsulated organisms such as Cryptococcus neoformans, S. pneumoniae, N. menin- gitidis , and H. influenzae type b (before the vaccine) are a cause of significant morbidity and mortality in neonates and children who lack protective anticapsular antibodies. Some bacterial, fungal, and parasitic pathogens avoid phagocytosis by excreting leukocidin C toxins, which cause specific and lethal damage to the cell mem- brane of host neutrophils and macrophages. Other pathogens, such as the bacterial agents of salmonellosis,