308
U N I T 4
Infection and Immunity
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,
TABLE 14-2
Examples of Virulence Factors Produced by Pathogenic Microorganisms
Factor
Category Organism
Effect on Host
Cholera toxin
Exotoxin
Vibrio cholerae (bacterium)
Secretory diarrhea
Diphtheria toxin
Exotoxin
Corynebacterium diphtheriae (bacterium)
Inhibits protein synthesis
Lipopolysaccharide Endotoxin Many gram-negative bacteria
Fever, hypotension, shock
Toxic shock toxin
Enterotoxin Staphylococcus aureus (bacterium)
Rash, diarrhea, vomiting, hepatitis
Hemagglutinin
Adherence Influenza virus
Establishment of infection
Pili
Adherence Neisseria gonorrhoeae (bacterium)
Establishment of infection
Leukocidin
Evasive
S. aureus
Kills phagocytes
IgA protease
Evasive
Haemophilus influenzae (bacterium)
Inactivates antibody
Capsule
Evasive
Cryptococcus neoformans (yeast)
Prevents phagocytosis
Collagenase
Invasive
Pseudomonas aeruginosa (bacterium)
Penetration of tissue
Protease
Invasive
Aspergillus (mold)
Penetration of tissue
Phospholipase
Invasive
Clostridium perfringens (bacterium)
Penetration of tissue
Botulinum toxin
Exotoxin
Clostridium botulinum (bacterium)
Neuroparalysis, inhibits acetylcholine release
Pneumolysin
Exotoxin
Streptococcus pneumoniae (bacterium)
Inhibition of respiratory ciliated and
phagocytic cell function
