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Host Microbe Interactions
Host Microbe Interactions
daily we
– ingest thousands of microorganisms on the food we
eat
– inhale hundreds of thousands of microorganisms in
the air we breath
– have microorganisms stick to us wherever we go
most of these invaders have no ill effect on us as we
cough, urinate and defecate them away
we are also protected by the “friendly” resident
microorganisms found throughout our body
Host Microbe Interactions
microorganisms very easily colonize the warm, moist,
nutrient rich environment we call the human body
– usually they live as normal flora
– in some cases, they are able to overcome the bodies
defenses, and cause disease
– organisms that can cause any noticeable damage,
invade tissue, or produce toxins are called pathogens
Anatomical Barriers
in addition to providing barriers to the microbial
world, skin and mucous membranes also create an
environment for interacting microorganisms and the
human body
these interactions are referred to as symbiosis,
which means living together
Anatomical Barriers
symbiotic relationships between microorganisms and a
host include
– mutualism
– commensalism
– parasitism
Mutualism
in this type of relationship, both partners benefit
– E. coli synthesizes vitamin K in the intestine
– in exchange the large intestine provides nutrients
necessary for survival of the microorganisms
E. coli
Commensalism
one organism is benefited and the other is unaffected by
this type of relationship
– many of the microorganisms that make up our normal
flora inhabit places like the eyes, ears, and external
genitalia
these bacteria live on secretions and sloughed off
cells
they bring no benefit to the host and yet the
microorganisms benefit greatly from the
environment they inhabit
Parasitism
one organism benefits at the expense of the other
– all pathogens are parasites
parasitic microorganisms
Normal Flora
microorganisms that colonize a host without causing
disease
two types of normal flora exist
– resident flora are microorganisms that inhabit sites on
the body for extended periods
– transient flora are microorganisms that are temporary
Normal Flora
the presence of normal flora
– cover potential adherence sites for invading
microorganisms
– consume the available nutrients
– produce compounds toxic to other microorganisms
bacteria found on skin
Normal Flora
when the balance between normal flora and
pathogens is upset, disease can result
– the normal bacterial microorganisms of the adult
human vagina maintain the pH at about 3.4 – 4.5
– the presence of this normal flora inhibits the
overgrowth of Candida albicans, yeast
Normal Flora
– if the presence of the normal flora is eliminated by
antibiotics, or excessive douching, the pH of the
vagina becomes nearly neutral, creating an
environment very conducive to the growth of C.
albicans
C. albicans
Principles of Infectious Disease
a parasitic relationship between a microorganism and a
host is called an infection
– infections can be subclinical or inapparent: meaning
no symptoms or the symptoms are so mild as to be
noticed
infection that causes impairment of body function is
called disease
Principles of Infectious Disease
the more virulent a pathogen is the more disease
promoting attributes it possesses
– virulence factors are substances or features of a
microorganism that help it infect and cause disease
– they may include
ability to adhere
ability to overcome host defense
ability to evade host defense
Establishing the Cause of Infectious
Disease
Koch’s Postulates
– criteria for establishing the fact that specific microbes
cause specific diseases
– determined by Robert Koch in 1877 while looking for
the causative agent for anthrax
Establishing the Cause of Infectious
Disease
1.
2.
3.
4.
Koch’s Postulates
– in order to determine that a microbe causes a
particular disease, the following postulates must be
met:
The microorganism must be present in every case of
the disease.
The organism must be grown in a pure culture from
diseased hosts.
The same disease must be produced when a pure
culture of the organism is introduced into a susceptible
host.
The organism must be recovered from the
experimentally infected hosts.
Mechanisms of Pathogenesis
pathogenesis is the manner in which a disease develops
– patterns that disease-causing microorganisms may
follow include
production of ingested toxins
– foodborne intoxication
– the causative agent must produce toxins
– few organisms are capable of causing disease
this way, the few that can include Clostridium
botulinum or Staphylococcus aureus
Mechanisms of Pathogenesis
colonization of host surface, then toxin production
– invading pathogen is able to grow to high
numbers on host surfaces such as the
respiratory and intestinal tract
– they then produce a toxin that is damaging to
the cells
– organisms that use this mechanism include
Vibrio cholerae, which causes cholera or
Corynebacterium diphtheriae, which causes
diphtheria
Mechanisms of Pathogenesis
invasion of host tissue
– breaching body’s barriers then multiplies in the
body’s tissues
– these organisms have mechanisms that allow
them to avoid macrophage destruction
– some are also capable of avoiding detection by
antibodies
– organisms that use this mechanism include
Mycobacterium tuberculosis, causative agent
for tuberculosis, and Yersinia pestis, causative
agent for plaque
Mechanisms of Pathogenesis
invasion of tissue, then toxin production
– breach the body’s barriers, then make toxins
– in addition to invasion, these organisms also
make toxins
– organisms that use this mechanism include
Shigella dysenteriae and Streptococcus
pyogenes
Mechanisms of Pathogenesis
in order to cause disease microorganisms need to be
able to
– adhere and colonize host tissue
– avoid the innate defenses
– avoid the adapted defenses
– cause damage related to the disease
Adherence
to establish disease the causative agent needs to
– adhere
difficult to overcome our first-line defenses so
adherence is imperative
many bacteria have adhesions, generally found on
the pili
Colonization
causative agent needs to
– multiply in order to colonize
to multiply, they must compete successfully with
the normal flora for space and nutrients
– toxins that may be produced by the normal flora
must be overcome
Avoiding Innate System
while some bacteria are able to cause disease while
remaining on the surface of the skin or mucosa,
many need to penetrate that barrier
once this is done, those pathogens have it on easy
street, exclusive rights to rich nutrition and
multiplying without any competition
penetrating the skin is extremely difficult
– bacteria take advantage of trauma to provide a
break in the skin
– West Nile Virus is transmitted to the host through
a mosquito bite, a penetration of the skin
Avoiding Innate System
mucous membranes penetration is the most common
entry for most microorganisms
– one method that is used is referred to as ruffling
once the microorganism attaches to the
membrane, it can direct the that cell to engulf the
bacterium: this is referred to as ruffling
ruffling on the surface of
mucous membrane
Avoiding Innate and Adaptive System
several mechanisms can be used by microorganisms to
avoid the potentially lethal effects of our immune system
– hide inside a host cell
phagocytes, complement and antibodies can’t find
them: remember self and non-self!
– interfere with the activation of complement (which
attracts phagocytes)
Avoiding Innate and Adaptive System
avoid destruction by phagocytes by simply preventing
encounters with phagocytes
– C5a peptides are an enzyme that is made by some
bacteria
– C5a peptide destroys the complement component
if the complement is not activated, neither are the
phagocytes
– some bacteria produce membrane-damaging toxins
that kill phagocytes
Avoiding Innate and Adaptive System
avoid recognition and attachment to phagocytes by
– producing capsules to prevent phagocytosis
Streprococcus pneumoniae procduces capsules
survive in the phagocyte
– they don’t worry about being engulfed, simply enjoy
the “free ride”
some microorganisms can escape from the
phagosome before being fused with the enzyme
lysosome
Hal 58
Avoiding Innate and Adaptive System
survive in the phagocyte
– some microorganisms can block the fusion of the
phagosome and lysosome
– a few organisms can actually survive the lysosome
environment
Avoiding the Adaptive System
avoiding antibodies which integral to the adaptive
system; this can be accomplished several ways including
– IgA protease
cleaves IgA class of antibodies found in mucus
and other secretions
– antigenic variation
alter structure of antigens
stay ahead of antibody production and destruction
by altering the structure the antibodies are
searching for
– mimic host molecules
some microorganisms have the ability to cover
themselves with molecules similar to “self”
Host Damage
in order for disease to happen damage of some sort
must happen to the host
– in most cases damage to the host facilitates dispersal
of the pathogen
damage to the host can occur either
– directly
– indirectly
Direct Host Damage
toxins produced by the invading pathogen cause direct
damage to the host which results in disease
toxins capable of causing damage include
– exotoxins
a protein toxin released from a living cell
mostly found in Gram + cells
Bacillus anthraxis
produces an exotoxin
Toxins
Some bacteria release poisons known as
toxins which cause food poisoning.
Some toxins, known as exotoxins multiply in
food. These toxins are not easily destroyed
by cooking and may remain in food once
they have developed.
Other bacteria produce toxins inside the
human body only after the food has been
eaten. These are called endotoxins
Exotoxins
exotoxins are secreted by the bacteria or released
following lysis
exotoxins are soluble in body fluids which makes them
easily diffused into blood and then are rapidly
transported throughout the body
exotoxins work by destroying particular parts of the host
cells or by inhibiting certain metabolic functions
Exotoxins
exotoxins are highly specific
exotoxins are among the most lethal substances known
to man
– 1 gram of the exotoxin produced from Clostridium
botulinum is capable of killing the entire population of
the United States, close to 300 million people
the danger with exotoxins is not the ingestion of the
bacterium, but the ingestion of the toxin
Clostricium botulinum
Exotoxins
most exotoxins are grouped according to the tissues
they adversely impact
– neurotoxins damage the nervous system
– entereotoxins upset the intestinal system
– cytotoxins afflict their damage on many different types
of cells by disrupting cellular function of by lysing the
cell
Endotoxins
endotoxins are lioopolysaccharides (LPS) found in
the lipid portion of the outer wall of Gram – bacteria
– endotoxins are released when Gram – bacteria die
and the cell wall undergoes lysis
antibiotics that are used to treat Gram –
diseases can lyse the bacterial cells, releasing
the endotoxin
– this can lead to an immediate worsening of
the symptoms
– these symptoms usually improve as the
endotoxins break down
Endotoxins
endotoxins can also activate blood-clotting proteins,
causing the formation of small blood clots
– blood clots obstruct capillaries, resulting in decreased
blood supply, which can lead to tissue death
this is referred to as disseminated intravascular
coagultaion
endotoxins also cause fever (pyrogenic response) and
rapid blood pressure decrease
Immune Response Damage
inflammatory response can destroy tissue
– antibody-antigen complexes formed during the
immune response settle in kidneys and joints
activates complement, which produces damaging
inflammation
Thank you
Principles of Infectious Disease
pathogenicity is the ability of a microorganism to cause
disease by overcoming the host defenses
– this can be accomplished with
a primary pathogen: microorganism capable of
causing disease in a healthy host
opportunistic pathogen: is only capable of
causing disease when the immune system is
overcome, or the organism is introduced to an
unusual location
– opportunistic organisms can be part of the
normal flora or found in the environment
A closer look at intestinal bacteria
Lactobacillus
 E. coli
Bifidobacterium
 Bacteroides
Staphylococcus
C. perfringens
Viral Pathogenesis Mechanisms
viral pathogenesis is very dependent on
– gaining access to the host
– evading the host’s defenses
– causing damage to or death of the host cell while
continuing to reproduce themselves
viral access to the host was discussed in the virus
lecture; remember viral attraction is specific to the host
– viruses bind more successfully to organisms found in
mucous membranes
Viral Evasion of Host
interferons play a role in limiting the ability of viruses
moving from neighbor cell to neighbor cell
– once infected cells are capable of producing a protein
that can regulate and limit viral replication
some viruses are able to encode proteins to shut
down this cellular protective device
Viral Evasion of Host
though limited in the ability to control viruses, those few
antibodies that are used can be circumvented by viruses
that have developed methods to transfer directly from
one cell to its immediate neighbor
– since antibodies control viruses by neutralizing
extracellular viral particles, the above renders this
useless
Terminology of Infectious Diseases
communicable
– disease that spreads from one host to another, either
through direct or indirect contact
infectious dose
– # of microbes needed to establish infection
some microorganisms are less contagious than
others and as a result require a larger number of
pathogens present to establish disease
Terminology of Infectious Diseases
sign
– objective changes that are observable and
measurable
– examples of signs include swelling, fever, paralysis
symptoms
– subjective effects experienced by patient
– examples of symptoms include pain or nausea
Terminology of Infectious Diseases
disease stages
– incubation
the time between the initial infection and the first
appearance of any signs or symptoms
this time can vary depending on the pathogen and
the condition of the host
– illness
signs and symptoms of the disease are experienced
if the disease is not successfully overcome or
treated, the patient dies during this period
– convalescence
person regains strength and the body returns to its
pre-diseased state
Terminology of Infectious Diseases
types of infectious diseases
– acute disease
rapid onset, short duration
influenza is an acute disease
– chronic disease
develop slowly, last longer
the body’s reaction may be less severe
hepatitis B is a chronic disuse
– latent disease
causative agent is never completely eliminated
remains inactive, but can become reactivated and
symptomatic if immune response is diminished
shingles is a latent disease
Terminology of Infectious Diseases
localized infections
– invading microorganisms are limited to a small area
– boils and abscesses are local infections
systemic infections
– infectious agent spread throughout body by blood or
lymph
– measles is a systemic infection
Virus and Host Damage
some viruses take-over and destroy the cell
virus causes inflammatory response – more damage –
more activation of inflammatory response
– often times, in particular with the case of the common
cold, the inflammatory response initiated by the virus
causes much less effect than the domino effect of the
inflammatory response that follows
Mechanisms of Eukaryotic
Pathogenesis
these mechanisms are not clearly understood, though
the mechanisms include colonization of the host, evasion
of the host defenses and damage to the host
fungi
– these organisms are generally opportunistic, taking
advantage of a weakening or change in our immune
system
excessive growth of Candida albicans is often a
result in immunocompormised hosts
– C. albicans is the causative agent of thrush, a
common occurrence in AIDS patients
Mechanisms of Eukaryotic
Pathogenesis
eukaroytic parasites
– are generally found in the intestinal tract or have
gained access through an insect bite
– attach with specific receptors
– are capable of hiding within the host cell
– the damage they can inflict varies
some cause malnutrition by competing for
nutrients
some can cause direct damage by the enzymes
they produce