C h a p t e r 1 4
Mechanisms of Infectious Disease
307
that an infectious agent survive the low pH and enzyme
activity of gastric secretions and the peristaltic action
of the intestines in numbers sufficient to establish infec-
tion, deemed an infectious dose. Ingested pathogens also
must compete successfully with the normal bacterial
flora of the bowel for nutritional needs. Persons with
reduced gastric acidity because of disease or medication
are more susceptible to infection by ingestion because
the number of ingested microorganisms surviving the
gastric environment is greater. Ingested pathogens also
must compete successfully for nutrients with the nor-
mal bacterial flora of the colon. Ingestion has also been
postulated as a means of transmission of HIV infection
from mother to child through breast-feeding.
Inhalation.
The respiratory tract of a healthy person is
equipped with a multilayered defense system to prevent
potential pathogens from entering the lungs. The sur-
face of the respiratory tree is lined with a layer of mucus
that is continuously swept up and away from the lungs
and toward the mouth by the beating motion of ciliated
epithelial cells. Humidification of inspired air increases
the size of aerosolized particles, which are effectively
filtered by the mucous membranes of the upper respira-
tory tract. Coughing also aids in the removal of particu-
late matter from the lower respiratory tract. Respiratory
secretions contain antibodies and enzymes capable of
inactivating infectious agents. Particulate matter and
microorganisms that ultimately reach the lungs are
cleared by phagocytic cells.
Despite this impressive array of protective mecha-
nisms, a number of pathogens can invade the human body
through the respiratory tract, including agents of bacterial
pneumonia (
Streptococcus pneumoniae, L. pneumophila
),
meningitis (
Neisseria meningitidis, Haemophilus influen-
zae
), and tuberculosis, as well as the viruses responsible
for measles, mumps, chickenpox, influenza, and the com-
mon cold. Defective pulmonary function or mucociliary
clearance caused by noninfectious processes such as cystic
fibrosis, emphysema, or smoking can increase the risk of
inhalation-acquired diseases.
Source
The source of an infectious disease refers to the location,
host, object, or substance from which the infectious
agent was acquired: essentially the “who, what, where,
and when” of disease transmission. The source may be
endogenous (acquired from the host’s own microbial
flora, as would be the case in an opportunistic infec-
tion) or exogenous (acquired from sources in the exter-
nal environment, such as the water, food, soil, or air).
The source of the infectious agent can also be another
human being, as from mother to child during gestation
(congenital infections); an inanimate object; an animal;
or a biting arthropod. Inanimate objects that carry an
infectious agent are known as
fomites
. For example,
rhinoviruses and many other nonenveloped viruses can
be spread by contact with contaminated fomites such
as handkerchiefs and toys. Zoonoses are a category of
infectious diseases passed from other animal species
to humans. Examples of zoonoses include cat-scratch
disease, rabies, and Creutzfeldt-Jakob disease (vCJD).
The spread of infectious diseases such as Lyme disease
through biting arthropod vectors has already been
mentioned.
Source can denote a place. For instance, infections
that develop in patients while they are hospitalized are
called
nosocomial
or
hospital acquired
, and those that
are acquired outside of health care facilities are called
community acquired.
The source may also pertain to
the body substance that is the most likely vehicle for
transmission, such as feces, blood, body fluids, respira-
tory secretions, and urine. Infections can be transmit-
ted from person to person through shared inanimate
objects (fomites) contaminated with infected body
fluids. An example of this mechanism of transmission
would include the spread of the HIV and hepatitis B
virus through the use of shared syringes by intravenous
drug users. Infection can also be spread through a com-
plex combination of source, portal of entry, and vec-
tor. Infection with hantavirus pulmonary syndrome is
a prime example. This viral illness is transmitted from
mice to humans by inhalation of dust contaminated
with saliva, feces, and urine of infected rodents.
Mechanisms of Disease Production
Infectious agents establish infection and damage tissues
by entering host cells and directly causing their death;
by inducing host responses that, although directed
against the invader, cause additional tissue damage; and
by generating
virulence factors
, substances or products
generated by infectious agents that enhance their ability
to cause disease. Although a large number of microbial
products fit this description, they can be grouped into
four categories: toxins, adhesion factors, evasive fac-
tors, and invasive factors (Table 14-2).
Toxins
Toxins are substances that alter or destroy the normal
function of the host or host’s cells. Toxin production
is a trait chiefly monopolized by bacterial pathogens,
although certain fungal and protozoan pathogens also
produce substances toxic to humans. Bacterial toxins
have a diverse spectrum of activity and exert their effects
on a wide variety of host target cells. For classification
purposes, however, the bacterial toxins can be divided
into two main types:
endotoxins
and
exotoxins.
Bacterial endotoxins
are lipopolysaccharides (LPS)
found in the cell wall of gram-negative bacteria. Free
LPS attaches to a circulating LPS-binding protein, and
the complex then binds to specific leukocyte receptors
that participate in activation of the innate immune sys-
tem (see Chapter 15). The host response to low levels
of LPS induces many important cytokines, as well as
expression of costimulatory molecules, resulting in leu-
kocyte recruitment and enhancement of T-lymphocyte
activation. However, at high levels, LPS can precipitate
septic shock, disseminated intravascular coagulation,
and acute respiratory distress syndrome.
