Human Microbe Interactions
In this lecture we will look at
microbial pathogenesis and
epidemiology.
• Pathology: the scientific study of disease.
– Concerned with etiology as well as structural and
functional changes brought about by the disease.
• Etiology: what caused the disease?
• Infection: invasion and colonization of body by
pathogenic microorganisms.
– Infection may exist in spite of an absence of detectable
disease.
• Disease: occurs when an infection results in any
change from a state of health
– An abnormal state in which part or all of body is
incapable of performing normal functions.
Normal Microbiota
• # of body cells in an average individual = 1 x 1013
• # of bacterial cells that inhabit an individual’s
body normally = 1 x 1014
• The microbes that normally inhabit a healthy
individual’s body is called normal microbiota or
normal flora.
• Microbial antagonism: normal microbiota can
benefit host by preventing overgrowth of harmful
microorganisms. In other words, the good
bacteria help defend against the bad bacteria.
– The good bacteria defend against the bad
bacteria by:
• Competing for attachment sites.
• Competing for nutrients.
• Making antibiotics against invading microbes.
– Disease occurs when this balance between the
normal flora and the host is upset.
• For example the use of antibiotics kills not just
invading bacteria but the normal flora as well,
leaving attachments sites available, more nutrients
available, etc. This in turn leads to increased risk
for another infection.
– An infection that results from a prior infection
is called a secondary infection.
Events in Infection
• Becoming Established: There are 3 main
factors that aid a microbe in becoming
established.
– 1. It enters the body through the correct portal
of entry.
– 2. The number of cells that enter the body is
enough to escape the body’s defenses.
– 3. Other predisposing factors that may make
the host more susceptible to disease.
– Portal of Entry: ways to enter the host
• Microbes can’t cause disease unless they enter the
body through the right opening.
– For example, if you eat a cold virus, you won’t get a cold.
• The body has 3 main ways that microbes enter.
• 1. Mucous membranes: respiratory tract (RT),
gastro-intestinal tract (GIT), urogenital tract (UT),
Conjunctiva (membranes that line the eyes).
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RT-inhale droplets of moisture or dust
GIT-food and water, fingers, pencils
UT-sexual intercourse
Conjunctiva-rubbing eyes with dirty hands.
• 2. Skin: unbroken, impenetrable to most people
– Can gain access through hair follicles, sweat ducts,
abraisons
• 3. Parenteral Route: deposited directly into tissues
beneath skin
– Punctures, injections, cuts, wounds, surgery, cracking
– 2. Size of Innoculum: number of cells that
enter through the portal of entry
• ID (Infectious Dose): minimum number of cells
required to cause infection
• Some organisms require 100’s of cells to cause
infection while others require as few as 10.
• 3. Predisposing Factors: one that makes the body
more susceptible to a disease and may alter the
course of the disease
– Gender
• For example, urinary tract infections occur more often in
females simply because their anatomy is such that fecal
material can easily enter the urinary tract leading to infection
by E.coli.
– Climate and weather
• For example, winter weather brings on more dry air. The dry
air dries out mucous membranes causing them to be more
susceptible to invasion.
• Winter weather also results in more people crowding together
indoors creating more opportunities for infection to spread.
– Others include nutrition, age, fatigue, etc.
Attachment
• After the microbe has entered the body, the
next step is to attach and colonize the body
surfaces.
– Adhesion: fimbriae, surface proteins, and
capsules are used by microorganisms to adhere
to and colonize body surfaces.
– Mechanical means such as suckers, hooks, and
barbs are used by parasites, such as tape worms,
to adhere and colonize body surfaces.
Surviving Host Defenses
• Once the organism has made it into the body and
attached it still has to avoid or defend itself from
the bodies internal defenses, the immune system.
– Avoiding Phagocytosis: some white blood cells gobble
up cells that don’t belong in the body, break them down
and discard the garbage. That process is called
phagocytosis.
• Capsules or other disguises are used by microorganisms to
avoid these vacuum cleaners of the cells.
– Some microorganisms make chemicals that are toxice
to white blood cells called Leukocidins
Process of Disease
• Stages of Disease
(See Pg. 396 tan box)
– Incubation period: time interval between the initial
infection and the first appearance of any signs or
symptoms. (in other words, no signs or symptoms but
the organism has entered the body).
– Prodromal period: short period that follows the
period of incubation in some diseases
• Early, mild symptoms
• You’re just starting to feel that a cold may be coming on, a
scratchy or mildly sore throat.
– Period of Illness: most acute stage of the illness. The
person exhibits full signs and symptoms of the disease.
• Number of white cells increases or decreases.
• If the patient were going to die, death would occur during this
period.
– Period of Decline: signs and symptoms subside.
• Patient is susceptible to secondary infections. The immune
system has just fought off an infection and the body is
weak. It is the perfect time for a new infection to begin.
– Period of Convalescence: person regains strength and
the body returns to its pre-diseased state.
• The period during which the disease is spread is
dependent upon the infecting organism. For
example, some organisms are contagious before
signs and symptoms are manifest. Others are
contagious during the worst portion of the
manifest signs and symptoms.
• How disease is caused:
– Virulence factors: any characteristic or
structure of the microbe that helps it to establish
itself in the host or cause damage in the host.
• Exoenzymes: enzymes that break down and damage
tissues or dissolve host defense barriers
– Ie. Mucinase: digest protective coating on mucous
memb.
– Keratinase: digest principal components of skin and hair
– Collagenase: digest principal fiber of connective tissue
– Hyaluronidase: digests hyaluronic acid, substance that
cements animal cells together
– Toxins: chemical products that are poisonous
to other organisms.
• Toxemia: toxin spread by the blood from the site of
infection to other parts of the body.
• Intoxication: ingestion of toxin.
• Toxins named according to mode of action
– For example, neurotoxins affect the nervous system. An
example of a neurotoxin is tetanospasim. Tetanospasim is
the toxin made by Clostridium tetanii. This organism
causes the disease known as Tetanus. Tetanospasim binds
to nerve cells and blocks relaxation pathways, or in other
words it causes uncontrollable muscle spasms.
– Death occurs when the toxin affects the function of the
heart or lungs.
2 Types of Toxins
• 1. Exotoxins: made inside a living microbe,
released into surrounding environment.
– This type of toxin is usually carried on plasmids or
phages.
– They work by destroying host cells or blocking
metabolic fuctions
• 1. Cytotoxins: kill host cells (damage cell memb)
• 2. Neurotoxins: interfere with nerve impulse transmission
• 3. Enterotoxins: affect cells lining GIT
• The body produces antibodies to exotoxins
called antitoxins. The antitoxins help the
body fight off the effects of toxins made by
bacteria.
– Pharmaceutical companies inactivate toxins
with heat and use them as vaccinations for
some diseases, such as the tetanus shot.
– Altered exotoxins are called toxoids.
– Ex. Clostridium tetani , tetanus toxin
• Endotoxins: are part of the LPS in the outer
membrane of the G- cell wall.
– When the G- bacteria die, the cells are lysed
which liberates the toxin.
– Responses by host are fever, chills, weakness,
aches, and in some cases leads to shock and
death.
– Endotoxins can also induce miscarriage and
activate blood clotting proteins which can in
turn lead to heart attack or stroke.
• Septic shock: is the life threatening loss of blood
pressure.
– Phagocytosis of G- bacteria causes the phagocyte to
release tumer necrosis factor (TNF).
• TNF damages capillaries causing them to become more
permeable. As a result, they loose large amounts of fluid and
more bacteria can cross the barrier.
• Shock is when large amounts of fluid are lost the blood
becomes thick and it is difficult for the heart to continue
pumping the blood through the body. The organs eventually
fail and the patient dies.
• Endotoxin without live bacterial cells can still cause disease.
Remember that it is the lysis of G- bacterial cells that releases
the toxin which then results in shock and death.
Classifying Disease
• Symptoms: changes in body function
– ex. Malaise, lethargy
• Signs: measurable or observable changes
– Red throat
– fever
• Syndrome: a specific group of symptoms and
signs that always accompany a disease
– Ear infection: tugging pulling at ear, disinterest in
eating or sucking, crying at night, ear hurts,
inflammation in ear canal, perhaps a slight fever, etc.
• Communicable Disease: spreads from host
to host either directly or indirectly
– Ex. Herpes: type 1 causes cold sores. Spread
by direct contact with open sore.
• Contagious Disease: disease that is easily
spread from person to person
– chickenpox
• Noncommunicable Disease: not spread
from host to host
– Tetanus, acquired by coming into contact with
organism in the environment.
Pathologic Effects of Disease
• Local infection: invading microorganisms
are limited to small area of body (boils)
• Systemic: microorganisms or their products
spread throughout body (tetanus).
• Focal infection: local infection spreads to
other areas of body where they are confined
– Ex. Infection in tooth causes sinus infection
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Bacteremia: presence of bacteria in blood
Septicemia: bacteria multiply in blood
Viremia: presence of viruses in blood
Toxemia: presence of toxin in blood
Primary infection: acute infection that causes
initial infection.
• Secondary infection: caused by opportunistic
pathogen after primary infection weakened the
body’s defenses.
• Subclinical infection: one that does not cause
any noticeable illness.
Severity or Duration of Disease
• Acute: develops rapidly, but lasts a short time.
(several days).
– cold
• Chronic: develops more slowly, disease is
continual, or recurrent for long periods (can last
for months or years).
– Mono
• Subacute: a disease that is in between
• Latent: causative agent remains inactive for a
time but becomes active with certain triggers
– Cold sores brought on by stress
• Rate at which disease spreads and the number of
people involved are determined partly by the
immunity of the population.
– The immunity of the population is determined by the
number of people who are current on their vaccines and
the number of people who have had previous exposure
to a particular organism.
• Herd immunity: means that many people in
community are immune to a particular organism.
They help provide immunity to a small number of
individuals in the community who are not
immune.
Portals of Exit
• Org. have definite routes of exit for spread.
• Most common portals of Exit are the respiratory and GI
tracts.
– Exit in discharge from mouth and nose.
– Some exit through feces.
• Urogenital tract and reproductive tracts are also portals of
exit.
• Drainage from wounds and infected blood can also be
portals of exit.
• Keep in mind that an organism doesn’t cause disease
because it hates you and wants you to die, it causes disease
as a result of it’s efforts to stay alive and grow.
Epidemiology
• Epidemiology studies when and where diseases
occur and how they are transmitted.
• Epidemiologists look for factors and patterns
concerning the people who are affected by the
disease.
• Then he/she assembles and analyzes the data
collected such as age, sex, occupation, history of
immunization, presence of other diseases and
common history of affected individuals.
• Epidemiologists are also concerned with
methods of controlling disease in the future
with ways such as water treatment,
pasteurization, and food inspection.
Occurrence of Disease
• Incidence: # of people in a pop. who develop a disease
within a particular time period.
– For example Flu season is October through March. The incidence
of Flu would be the number of people reported to have been
diagnosed with Flu during those months.
• Prevalence: # of people in a pop. who develop a disease at
a specified time, regardless of when it first appeared.
– The prevalence of Flu in the population would be how many
people who had Flu on December 25.
• Sporadic Disease: disease only occurs occasionally. Not
predictable.
– Stomach flu, doesn’t coincide with any months of the year.
• Endemic Disease: disease constantly
present in a population
– Ex. Cold or stomach flu
• Epidemic Disease: many people in a given
area acquire a certain disease
– Usually a smaller area, such as a city, state,
continent. Ex. E.coli outbreak.
• Pandemic Disease: epidemic disease that
occurs worldwide
– AIDS is now considered a pandemic.
Reservoirs of Infection
• Reservoir of Infection: a continual source of the
organism that causes a particular disease.
– The source can be either living or inanimate. It simply
need to provide the pathogen with adequate conditions
for survival and multiplication and an opportunity for
transmission.
– Human: people who harbor a disease without signs or
symptoms (carrier) can be reservoirs of infection.
• HIV
• Herpes
• Animals can be reservoirs of infection.
– Diseases that primarily occur in wild and
domestic animals but can be transmitted to
humans are called zooneses.
• Ex. Rabies
– Transmission: direct contact with infected
animals, direct contact with infected waste,
contamination of food and water, air from
contaminated hides, fur, or feathers, consuming
infected animal products, or insect vectors
(fleas biting rats and then biting humans).
• Nonliving reservoirs: soil and water are
two major examples
– Ex. A deer infected with Giardia goes to a
beautiful mountain stream to take a drink and
defecates next to the water while there.
• An unsuspecting hiker sees the beautiful mountain
stream and takes a drink. (One case of Giardia
coming up….)
Transmission of Disease
• 3 principle routes:
– 1. Contact: direct contact, indirect contact,
droplet transmission
• Person to person: touching, kissing, sexual
intercourse
– AIDS, Mono, colds
• Transmission through fomites. Fomites are
inanimate objects that can carry the disease.
– Kleenexs, bedding, diapers, drinking cups, eating utensils,
money, thermometers, syringes, etc)
» AIDS, Hepatitis B
• Droplet: Coughing, sneezing, laughing, talking
– Influenza
– 2. Vehicle: transmission by a medium such as
water, food, or air
• Food poisoning
• Giardia
• Fungal spores in air
– 3. Vectors:
• Mechanical transmission: passive transport of org.
on insects body or feet
– Flies can transport typhoid fever, shigellosis.
• Biological transmission: insect bites infected person,
transfers org. to an uninfected person upon biting
the new victim.
– Malaria, West Nile Encephilitis, etc.
Nosocomial Infections
• A nosocomial infection is an infection that
is acquired as a result of a hospital stay.
(You are admitted for one thing and acquire
an infection while there.)
• CDC estimates that 5%-15% of all hospital
patients acquire some type of nosocomial
infection.
– It happens because the hospital is a major
reservoir for a variety of pathogens;
– Hospitalized persons are in a weakened state
and more susceptible to infection;
• Resistance to infection is impaired by disease,
therapy, or burns
• Two principle conditions compromise host:
– Broken skin or mucous membranes
– Immunocompromised
• Risk of infection is also related invasive procedures
such as catheters, tracheotomy, injections,
intravenous catheters,
– There are more antibiotic resistant strains in
hospitals.
Transmission of Nosocomial
Infections
• Direct transmission from hospital staff to
patient and from patient to patient.
• Indirect contact transmission through
fomites and the hospital’s ventilation
system.
• Certain areas of hospital reserved for
specialized care such as burn, intensive
care, oncology to prevent nosocmial
infections.
Control of Nosocomial Infections
• Hand washing is the most important means
of preventing the spread of infection.
• Disinfection of tubs used to bathe patients,
humidifiers and respirators, and materials
used for bandages and intubation.
• Physicians should prescribe antibiotics and
immunosuppressive drugs only when
necessary.
How Scientists Discover the
Etiology of Infectious Disease
• Koch’s Postulates:
– 1. Same pathogen must be present in every case of the
disease
– 2. Pathogen must be isolated from the diseased host and
grown in pure culture
– 3. Pathogen from pure culture must cause the disease
when inoculated into a healthy, susceptible lab animal
– 4. Pathogen must be isolated from the inoculated
animal and must be shown to be the original organism.
Exceptions to Koch’s Postulates
• Org. such as Mycobacterium leprae, the organism
that causes leprosy, has never been grown on
artificial media because its growth requirements
are difficult to reproduce.
• Many other pathogens cannot be cultivated on
artificial media because they are obligate
intracellular parasites. That means they can only
grow within particular host cells.
• Some pathogens cause several diseases
– S. pyogenes can cause sore throat, scarlet fever, skin
infections, inflammation of bone, as well as others.
• Many org. that cause same kind of disease
such as pneumonia.
• For some diseases, the only host is humans.
For obvious reasons we can’t experiment on
humans.
• For the most part, the principles and steps
that Koch used almost 200 years ago to
identify Anthrax in sheep, are still
applicable today in identifying disease
causing organisms.
• No HW today.