Chapter 4 - Lesson 4

Host-Pathogen Interactions

Introduction Koch’s Postulates: Experimental Steps

to Determine Disease Causation
Microbes are found everywhere. On a daily basis we
ingest, inhale, and transport thousands of organisms Over a century ago, Robert Koch established that in-
(i.e., bacterial, viral, protozoal, or parasitic). Most fectious diseases were caused by microbes. He was
have no ill effects due to protective mechanisms in our looking for the causative agent for anthrax. Koch’s
body (i.e., coughing, urinating, sneezing, and defecat- postulates are experimental criteria that are used to
ing). Humans and animals have “friendly” organisms determine if a microbe caused a specific disease. The
throughout their bodies that survive as normal flora criteria include:
and colonize a host but do not cause disease. How-
ever, if these organisms begin to cause any obvious 1. The microbe must be present in every case of the
damage to a host by invading tissues and/or producing disease.
toxins, they then become pathogens. 2. The organism must be grown in a pure culture
from diseased hosts.
What is the significance of host-pathogen interactions? 3. The same disease must be produced when a pure
Host-pathogen interactions provide information that culture of the organism is introduced into a sus-
can help scientists and researchers understand disease ceptible host.
pathogenesis, the biology of one or many pathogens, 4. The organism must be recovered from the experi-
as well as the biology of the host. It is through these mentally infected hosts.
interactions that basic research discoveries are made.

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 Components ForThe Host Pathogen
However, there are some exceptions to these criteria.
These include:

1. Some organisms cannot be cultured in a lab and 4

A hosts immunologic
grown on artificial media. ability to eliminate or
control the microbe
2. Some pathogens can cause several disease condi-
tions such as M. tuberculosis, which can cause lung
disease and other diseases of the skin, bone, and in- 3 1
Microbe replication, Invasion of the
ternal organs. with or without host through primary
3. There may be ethical reasons that do not allow spread in the body barriers
testing, (i.e., human diseases with no animal mod-
el – smallpox, rubella). 2
Evasion of local
and tissue host
Host-Pathogen Interactions defenses by microbes

An individual’s or animal’s skin and mucous mem-

branes generate an environment for microorganisms
to interact with the body. This interaction between the Components for the host pathogen interaction.
host and the organism is referred to as symbiosis. There
are three forms of symbiotic relationships that can oc-
cur at an anatomical level. In order for this to take
place the following components will need to occur: available nutrients. For disease to occur there must be
a change in the body’s environment, which, in turn, al-
• Mutualism: In mutualism, both the microorgan- lows the pathogen to overcome the normal flora. This
ism and the body work together. An example of can occur through a change in the pH of the body or
this relationship would be cows and the bacteria elimination of normal flora due to antibiotics.
in their rumen. Bacterial cellulose facilitates di-
gestion in the animal, while the bacteria benefit Host Defenses
from nutrients in the rumen.
• Commensalism: In commensalism, either the A microorganism will not be able to invade unless it
body or the microorganism benefits, while the overcomes an animal’s or individual’s host defenses.
other is not affected by the interaction. Examples Specific host defenses may include:
of this include microorganisms that make up the
normal flora that inhabit the eyes. These organ- • Skin and mucosal secretions
isms thrive on secretions and dead cells, but do • Non-specific local responses (e.g., pH)
not affect the host. • Non-specific inflammatory responses
• Parasitism: In parasitism, one organism benefits • Specific immune responses (e.g., lymphocytes)
at the expense of the other. For example, parasites
use the gastrointestinal tract of a human or animal The ability for a pathogen to overcome host defenses
as an environment in which to reproduce. can be accomplished by two distinct components: a
primary pathogen (causes disease in a healthy host) or
The Body’s Normal Flora opportunistic pathogen (causes disease if host is im-
munocompromised).
The body contains two types of normal flora: 1) resi-
dent flora (survive for extended periods), and 2) tran- Pathogen Defenses
sient flora (temporary). Normal flora help to provide
defenses against invading pathogens by covering ad- Pathogens contain virulence factors that promote
herence sites, producing compounds toxic to other disease formation and provide the opportunity for a
organisms, and preventing pathogens from consuming microbe to infect and cause disease. The greater the

124 Chapter 4 - Biomedical Research

virulence, the more likely disease will occur. Such
factors include:

• Ability of a pathogen to adhere to a host 1 - Transmission

• Ability of a pathogen to colonize (overcome) a host
• Ability of a pathogen to evade host defenses
2 - Adherence

Mechanisms of Pathogenesis
3 - Invasion
Pathogenesis is the method by which a disease can de-
velop. This can occur through foodborne intoxication
where the causative agent produces toxins in the body 4 Colonization

(e.g., botulism). Another route is the colonization of

an invading pathogen on the host surface, which al-
5 - Evasion of host defenses
lows the pathogen to increase in numbers and produce
toxins that are damaging to the host’s cells (e.g., Vib-
rio and Corynebacterium). 6 - Damage and disease to host tissues

Pathogenesis can also occur by pathogens invading

and breaching the body’s barrier in order to multiply. 7 - Exit from the body
These organisms have mechanisms that will not allow
macrophages (the body’s defense against pathogens)
8 - Survival in the environment
to destroy them. They can also evade antibody detec-
tion (e.g., tuberculosis and plague). Finally, organisms
can invade tissues within the body and produce toxins
(e.g., Shigella).
Mechanisms of pathogenesis.
The relationship between a host and pathogen is dy-
namic. Production of disease occurs through a process
of steps. The first five mechanisms make up a patho-
gen’s invasiveness (i.e., ability to invade tissues). receptors or surface proteins. Pathogens may have
specific adherence mechanisms to attach to cells or
Transmission tissue surfaces. Examples of this include: 1) tissue tro-
pism (i.e., pathogens that prefer specific tissues over
In order to begin infection and eventually cause dis- others), 2) species specificity (i.e., pathogens that only
ease, pathogens must find a transmission route. Trans- infect certain species), and 3) genetic specificity (i.e.,
mission of an infectious agent can occur in many surface mutations that occur so previous antibodies do
ways, but it is typically through exposed skin (e.g., a not recognize the invading pathogen). If a microor-
cut, abrasion, puncture, or wound) or mucous mem- ganism cannot adhere to a host cell membrane, dis-
branes (e.g., gastrointestinal tract, respiratory tract, or ease will not occur.
urogenital tract).
Invasion
Adherence
At this point, microbes begin to invade the host and
Once the pathogen has gained access to the body, produce a bacteremia (i.e., presence of bacteria in the
it must have some means of attaching itself to the bloodstream) or viremia (presence of a virus in the
host’s tissues. This attachment is called adherence bloodstream). Microorganisms are exposed to many
and is a necessary step in pathogenicity. Microbes barriers after introduction into the host. Some bacte-
contain ligands, which are projections that attach host ria are able to cause disease while remaining on the

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epithelial barriers, while many need to penetrate that Three types of toxins are produced to cause damage:
barrier. Once this barrier has been penetrated, these
pathogens can multiply without competition. • Exotoxins: Proteins secreted by pathogens that
cause damage to the host (botulinum toxin, teta-
Colonization nus toxin, hemolysin (ruptures red blood cells).
• Endotoxins: Toxic substances that are released
Colonization is the multiplication of pathogenic or- when a cell is killed (Lipolysaccharides).
ganisms where toxins are produced and the normal • Exoenzymes: Enzymes that function outside the
flora are overcome. During this stage, pathogens host cells or tissues. These include coagulase
compete with normal flora for space and nutrients. (forms a fibrin clot that “hides” the microbe from
Pathogens usually colonize host tissues that are in phagocytosis), hyaluronidase (breaks connective
contact with the external environment. During colo- tissues down), or fibrinase (breaks down blood
nization, the host begins to show signs of septicemia clots to allow pathogens to continue spreading).
(i.e., blood infection where bacteria are reproducing).
For infection to proceed an infectious dose should be Exiting the Host
determined. This is the minimal number of microbes
necessary to establish infection. Certain pathogens are A pathogen must exit the body. This occurs through
less contagious and therefore require larger numbers various routes. Examples include sneezing, coughing,
of pathogens to cause disease (i.e., 10-100 for Shigella diarrhea, coitus, pus, blood, or insect bites.
and 1,000,000 for Salmonella).
Survival Outside the Host
Evasion of Host Defenses
Finally, a pathogen must be able to survive in the envi-
After colonization, pathogens circumvent the host’s ronment long enough to be transmitted to another host.
innate nd adapted defenses by phagocytosis. Multiple Some are hardy and can survive for several weeks be-
mechanisms are used by pathogens to evade a host’s fore a new host is found. There are others that survive
immune system. For the innate system this includes: in animal reservoirs or require direct contact because
they are fragile.
• Intracellular pathogens that live inside a host cell
• Avoid phagocyte recognition by producing cap-
sules prevents phagocytosis
• Producing membrane damaging toxins which can
kill phagocytes (e.g., leukocidins)
• Interfere with complement activation
• Survive in the phagocyte

Pathogens must also avoid adapted defenses. Patho-

gens can produce proteases (i.e., allow each pathogen
to avoid antibodies) or catalases (i.e., prevents the di-
gestion of an engulfed pathogen). They can also uti-
lize antigenic variation to alter the antigen structure.
In addition, pathogens can mimic host molecules,
which can cause disease-related damage.

Cause Damage or Disease to Host

While Avoiding Host Defenses

Damage can occur through direct or indirect path-

ways. Direct methods produce toxins, which are poi-
sonous substances that produce toxemia within a host. Mosquito. Photo, James Gathany, CDC.

126 Chapter 4 - Biomedical Research

 Pathogens may exit the body through a cough or sneeze. CDC.

Infectious Diseases: The Basics Disease Stages

An infectious disease is a clinically evident deviation Infections can be either subclicinical or inapparent. If
from health. It occurs when there is a parasitic rela- clinical signs are seen, disease occurs. The incubation
tionship between a host and a microorganism. Several period is the time between infection and first appear-
different factors influence a microorganism’s relation- ance of signs or symptoms. This period depends on
ship to its host and level of severity. These include: the dose level of microbes, microbe type, virulence,
and host health.
• Pathogenicity: The ability to produce disease in
a host organism. The prodromal period of 1 to 2 days follows incuba-
• Virulence: The degree of pathogenicity of a mi- tion in some diseases. This includes early, mild signs/
croorganism. Determinants of virulence for a symptoms such as, fatigue, muscle aches, and/or
pathogen include a pathogen’s genetic, biochemi- headache. Recovery occurs when signs/symptoms are
cal, or structural features. For example, one strain subsiding but the host may remain more susceptible to
of influenza may only cause a fever and sore throat, secondary, opportunistic infections. During the conva-
while another may cause pneumonia or other seri- lescent period, the body returns to a pre-diseased state.
ous respiratory condition.
• Infectivity: The level at which a microorganism Conclusion
is able to infect or invade a host.
• Transmissibility: The measure of a microorgan- Microorganisms are located everywhere, and there
ism’s ability to spread from one host to the next. are many more microbes than hosts. The goal for both
This can include both distance and number of af- host and microbe is survival. Infection can be local-
fected individuals. ized, focal, or occur systemically. Several factors af-
fect the balance between health and infectious disease.
Pathogenesis depends on genetics, the state of host
health, age, and stress.

Chapter 4 - Biomedical Research 127

References 2. Define the following terms:
a. Pathogenicity
Sparling, P. F. Bacterial virulence and pathogene- b. Virulence
sis: an overview. Rev Infect Dis. 1983;5 (Suppl. c. Infectivity
4):S637–S646. d. Transmissibility
3. Describe the mechanisms that must occur for
Wood, W. B., Davis, B. D. (1980). Host-parasite rela- pathogenesis to occur.
tions in bacterial infections. In: Davis, B. D., Dul- 4. What are the components needed for a host-patho-
becco, R., Essen, H. N., & Ginsberg, H. S. (Eds.), gen interaction to occur?
Microbiology. (pp. 551–571). Cambridge, MA: 5. What are the different disease stages?
Harper & Row.
Activity
Questions
1. Using the chart below, choose a disease agent and
1. What is symbiosis? write a sentence to describe each mechanism of
pathogenesis.

Activity: Mechanisms of Pathogenesis

In Animals
Disease Agent: (e.g., Brucellosis)
Agent

Transmission

Adherence

Invasion

Colonization

Evasion of host defense

Damage and disease to host tissues

Exit from the body

Survival in the environment

In Humans
Agent

Transmission

Adherence

Invasion

Colonization

Evasion of host defense

Damage and disease to host tissues

Exit from the body

Survival in the environment

128 Chapter 4 - Biomedical Research