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Host-Microbe Relationships and Disease
• Classical ecological definitions
– Mutualism: organisms live together, both benefit
• E. coli in GI tract; we get Vitamin K, protection from
pathogens, it gets warm wet place to live, lots to eat.
– Commensalism: one organism benefits, the other is not
particularly benefited or harmed; to eat at the same table
• Most GI tract microbes; we provide a warm wet place
to live with food, we don’t get all that much in return.
– Parasitism: one organism benefits at the other’s expense
• Disease-causing bacteria; to them, we’re dinner.
• Classically, a “parasite” lives in or on host.
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Terms, terms, and more terms
• Contamination: presence of microbes (where they don’t
belong).
• Infection: multiplication of parasitic organisms in/on host.
– Infestation: used to describe larger organisms, e.g. lice.
• Disease: malfunction in or damage to the host.
– Many kinds of “disease”; here we discuss “infectious
disease”.
– Disease is a condition of the host, not an infectious
microbe.
• Pathogen: a parasite capable of causing disease
– Not all pathogens are equal as we will see..
• Pathogenicity: ability of pathogen to cause disease
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Terms, terms, and more terms-2
• Virulence: relative ability to cause disease.
– Especially variations in pathogenicity w/in specific group
– Can be weakened (attenuation) or increased (animal
passage); Growing pathogens on agar attenuates them.
• Normal microbiota: the microbes normally found on the
body. Since people are not “normally” sick, pathogens are
not normally consider “normal microbiota”.
• “flora” is to be avoided as microbes are NOT plants!
– Resident microbiota: always found on human tissues.
– Transient microbiota: come and go, can include potential
pathogens.
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Where do they live?
• Microbes live where it is “topologically outside”
– We are a tube within a tube. We have sacs
open to the outside.
• Respiratory tract:
– nasal passages, sinuses, trachea, lungs. Lungs
well protected, other areas more populated.
• GI tract: Crowded!
– Mouth is full, fewer in esophagus and stomach; toward
end of small intestine, numbers increase greatly.
– Feces consist largely of bacteria.
http://www.radiation-scott.org/deposition/respfig2.gif
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Where do they live?-2
• Skin: largest organ in the body.
– Colonized. Various factors keep the numbers down.
• Genito-urinary tract:
– Female reproductive tract colonized, especially with
Lactobacillus which is helpful and with yeast which is
occasionally not helpful.
– Lower portion of urethra contains some bacteria, but
bladder, ureters, and kidneys normally sterile.
• All areas of the body have mechanisms for keeping
us from being lunch; to be discussed soon.
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What determines whether we get sick?
• Inf Dis: the likelihood of
contracting an infectious
disease.
• N: the numbers of infecting
organisms.
•V: the virulence of the organism.
•HF: host factors, including overall health, nutritional
status, genetic background, age, immune status.
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How dangerous?
• Pathogen: causes disease.
• Opportunistic pathogen: can cause disease under the
right circumstances
– Dose in high numbers
– Host is in a weakened state, e.g. HIV infection.
– Organism gets where it doesn’t belong
• E. coli and urinary tract infections.
– Lack of microbial antagonism, e.g. superinfection
• competition for space, nutrients; bacteriocins.
• Saprotroph: decompose dead stuff.
Whether an organism will cause disease
is not always a clear cut thing
8
• Not everything in biology can be neatly classified.
There is a gradation from pathogen to opportunist to
non-infectious, and what happens depends on the
balance of these 3 factors.
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Types of disease
•
•
•
•
Inherited diseases: caused by a faulty gene
Congenital: due to damage during development.
Degenerative diseases, due to age or lifestyle
Nutritional, endocrine, mental, immunological,
neoplastic (cancer), idiopathic; same caveat.
• Iatrogenic: caused by doctor.
– Nosocomial infections: occur in hospital.
• Infectious disease: caused by infectious agents
– Bacteria, viruses, fungi, etc.
– Infectious agents may affect other types of disease
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Types of infectious diseases
• Communicable: can be spread from one person to
another.
– Example: tuberculosis, HIV
• Contagious: highly communicable, can easily be
spread from one person to another.
– Genital herpes, measles.
• Non-communicable: are not spread from one host to
another.
– Examples: your infected appendix bursts
– You get tetanus from “rusty nail”
How bacteria cause disease
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• Bacteria can be invasive
– Bacteria spread through tissues, usually using
digestive enzymes which damage tissues, kill cells.
• Bacteria can be toxigenic (produce toxins)
– Bacteria may not spread, but release soluble toxins
which dissolve in body fluids, damaging cells.
– Gram negatives contain endotoxin (LPS)
• Host processes
– Host defenses, like inflammation, may overrespond, cause significant tissue damage.
Steps in an infectious disease-Overview
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• Entry and attachment
– Microbe needs to approach tissue, then attach to it.
• Deal with host defense
– Successful parasite must infect, persist long enough to
reproduce, then escape. Host defense seeks to kill it.
• Damage: if disease is involved, damage occurs.
• Escape: parasite must escape and spread to others.
– Discussed in “Portals of exit”
Virulence Factors: Things that bacteria have that
improve their abilities to cause disease
– Fimbriae, capsules, enzymes, toxins, all these things.
Typical steps in a bacterial infection
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• Attachment
– Typical first step is attachment to tissues. Often a
specific interaction takes place between molecules.
– Fimbriae, capsules help in attachment.
– Molecules that aid in attachment = adhesins.
• Deal with host defenses
– A pathogen can defend, attack, or hide.
• Interfere with phagocytosis, have a capsule, etc.
• Produce leukocidins, etc.
• Switch surface antigens, hide inside WBC, etc.
Step 3: Damage
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• Damage occurs from combination of factors
– Bacteria increase their growth by
• Releasing enzymes that break down host cell
molecules, releasing nutrients or allowing spread.
–Hemolysins release iron.
• Releasing toxins that kill cells or damage organ
systems, eliminating host resistance.
– Bacteria cause disease by
• Stimulating inflammation, leading to damage and
discomfort
• Over-stimulating host defense, damaging cells
and organ systems.
Virulence factors: enzymes and toxins
• Enzymes
– Coagulase, streptokinase.
– Allow spread or hiding of pathogen.
• Toxins
– Exotoxins, produced by G+ and G-, proteins, heat
labile, released and affect different targets
• Enterotoxins, neurotoxins, general cytotoxins.
– Endotoxin: LPS, especially Lipid A part
• Present only on Gram –
• Released when bacterium dies
–Acts as Super antigen
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Hijacking host defenses
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• Inflammation
– A protective mechanism, but can cause local
damage.
• Chronic inflammation results in loss of functional
tissue, disease.
• Super antigens
– Endotoxin, Toxic Shock Syndrome toxin, et al.
• Cause massive over response of WBCs
– Fever, shock, intravascular coagulation, emesis
• Over-response followed by under-response
Epidemiology and Disease terms
• Epidemiology is the study of disease:
– the study of the factors involved in the frequency
and spread of disease.
• Etiology
– The study of the causes of disease
• Signs and symptoms
– Signs are observable/measurable
– Symptoms are experienced by patient
• Syndrome: collection of signs and symptoms
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More epidemiology definitions
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• Incidence: # of new cases during a time period
• Prevalence: ongoing cases at any one time
– Both often expressed per number of people at risk
• Mortality and morbidity rate:
– Death and sickness per total population over a
given period of time.
– Many diseases have unique patterns, such as flu
occurring during the winter months.
The first epidemiological study
John Snow, London, 1854
The cause of cholera
wasn’t known, but Snow
guessed it was spread by
water. By mapping all the
known cases and
comparing them to the
sources of water, he
correctly identified the
source of the problem.
http://www.sfu.ca/gis/bguide/icons/figure1.4_snowmap.gif
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Terms-1
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• Acute, subacute, chronic
– Refers to how long the disease lasts
– Acute is short lived, subacute longer,chronic longest
• Local, systemic
– A local infection is in one specific place, systemic
means throughout the body.
• Primary, secondary, superinfection
– Primary: the first or main infection
– Secondary: a second infection once weakened by a
first one.
– Second infection usually blamed on antibiotic Rx
Terms-2
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• Bacteremia, viremia vs. septicemia (blood
poisoning)
– Bacteremia is a clinical finding: bacteria in the blood
– Septicemia is a disease condition, microbes actively growing
in, infecting blood.
– Viremia: viruses in the blood, common in systemic infections
• http://www.mansfield.ohiostate.edu/~sabedon/biol2040.htm
– Excellent web site with definition of many, many
terms related to infection and disease.
Susceptibility and transmission
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• Exogenous vs. endogenous
– Exogenous means infection comes from outside the
host. Examples: common cold, STD.
– Endogenous means host is original source of
infection. Examples: boils on skin spread by fingers
from Staph sinus infection; E. coli urinary tract
infection.
• Compromised host
– Weakened immune system, poor lung clearance
from bed rest, surgical wounds, bedsores, etc.
Where germs live: reservoirs
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• Humans
– May be sick, may be carriers
• Animals
– Many diseases are zoonotic but can also be caught
by humans; animal may be healthy or not.
• Non-living
– Soil, water are typical homes to microbes that can
cause disease.
The Ins and Outs of infections:
Portals of entry and exit
24
• The successful parasite has to get in, multiply,
then get out to spread to others.
• People have lots of entry points
– Glands, follicles that open to outside
– Larger openings: respiratory system, digestive
system, genito-urinary tract
– Cuts, bites, burns, surgical incisions
– Crossing the placenta, infecting the fetus
• Pathogens have favored portals of entry
– Some microbes aren’t harmful if portal is not optimal
Exit
25
• The portal of exit is often the same or connected to a
portal of entry
– Coughing sneezing speaking: from mouth
– Excretory systems: GI tract, in feces; in urine
– From sex: vaginal fluid, semen
– From blood: insect bites, shared needles
http://www.humboldtredwoods.org/images/mosquito.jpg
Transmission
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• Microbe needs to get from reservoir to you.
• Contact
– Direct contact: touching, kissing, sex, endogenous
spread (one part of you to another)
– “vertical”: mother to offspring, e.g. transovarian
– Indirect contact, via fomites (inanimate objects)
– Droplet transmission:
less than 1 meter thru air
WASH YOUR HANDS!!!!
http://students.washington.edu/grant/random
/sneeze.jpg
Transmission-2
• Vehicles
– Water: various viruses, bacteria,
protozoa, mostly that cause diarrhea
and enter water supply.
– Food: unpasteurized or contaminated
food, either improperly grown,
processed, or prepared.
– Airborne: microbes attached to dust,
skin flakes, dried mucus become
aerosols, travel thru air.
http://www.kennethkeith.com/milkgreeceb.JPG
27
Transmission-3
28
• Vectors
– Typically arthropods (insects, ticks)
– Mechanical vectors: simply spread disease, e.g.
houseflies walking on feces, spread germs to
humans.
– Biological: pathogen goes through part of life cycle
in vector
• Viruses or protozoa that reproduce within
mosquito, e.g. Major method for spread of
zoonoses.
http://www.doktordoom.com/images/Tick.jpg
Koch’s Postulates
29
• Historical context:
– So many germs, so many diseases
– Logical framework for matching them
1. Microbe must be found in every instance of the
disease.
2. Obtain microbe in pure culture
3. Produce disease in susceptible host
4. Re-isolate original microbe
http://www.nsc.gov.tw/files/popsc/2003_276/9208-13-04.jpg
Stages of Disease
• Incubation
• Prodromal
• Illness
(acute/invasive)
• Decline
• Convalescent
Stages for acute disease; chronic lasts longer.
http://www.goshen.edu/bio/NaSc104/graphics/stages.jpg
30
Distribution of diseases in time and space
• Some diseases, such as influenza, are
seasonal.
http://www.phacaspc.gc.ca/publicat/ccdrrmtc/03vol29/images/2906f
g3.gif
• Some diseases are found only in some
geographic areas
http://whyfiles.org/016skeeter/images/malari
a_distribution_2000.gif
31
Frequency of disease terms
•
•
•
•
Endemic: continually present in low numbers
Epidemic: higher than normal occurrence
Pandemic: epidemic spreads worldwide
Sporadic: cases show up only occasionally
http://www.cdc.gov/mmwr/preview/mmwrhtm
l/figures/00000122.gif
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Herd Immunity
Herd immunity: indirect
protection from disease
due to there being a high
number of immune
individuals in the
population.
The more immune
individuals, the harder it
is for the disease to be
spread among many
people; the cycle of
transmission is broken.
33
http://wwwmicro.msb.le.ac.uk/3035/3035pics/Herd.gif
Notifiable diseases
34
• Notifiable disease: potentially harmful diseases
which must be reported to the CDC or other
Health Unit by physicians
– Allows CDC to keep track and intervene.
– Some examples listed by Arkansas Dept. of Health:
• Anthrax, Botulism, Hepatitis A,
• Pertussis, Plague, Q Fever, SARS, Smallpox,
• Tularemia, Typhus,
• Viral Hemorrhagic Fevers