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Transcript
How bacteria cause disease
1
• 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 negative contain endotoxin (LPS)
• Host processes
– Host defenses, like inflammation, may overrespond, cause significant tissue damage.
Disease by other microbes
• How viruses causes disease
– Viruses multiply inside host cells, using cell
resources, often killing cells.
– Viruses stimulate the immune system to fight back;
infected cells are killed.
– Viruses alter cell cycle regulation to promote their
own replication; may lead to cancer.
• Fungi, Protists, and worms
– Produce enzymes that damage host cells
– Multiply in host cells and kill them
– Cause allergic reactions or inflammation
2
Steps in an infectious disease-Overview
• 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.
3
Virulence factors: enzymes and toxins
• Enzymes
– Collagenase, hyaluronidase, 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
4
Hijacking host defenses
• 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 WBS
• Fever, shock, intravascular coagulation
5
Epidemiology
• Epidemiology is the study of disease:
– the study of the factors involved in the frequency
and spread of disease.
• Incidence: # of new cases during a time period
• Prevalence: ongoing cases at any one time
• 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.
6
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.gisdevelopment.net/application/health/overview/images/image1.jpg
7
Where germs live: reservoirs
8
• 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
• The successful parasite has to get in, multiply,
then get out to spread to others.
• People have lots of entry points
9
– 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
10
• 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/mosqu
ito.jpg
Transmission
11
• 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
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
12
Transmission-3
13
• 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.
Susceptibility and transmission
14
• 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.
Koch’s Postulates
15
• Historical context:
– So many germs, so many diseases
– Logical framework for matching them
• Microbe must be found in every instance of the
disease.
• Obtain microbe in pure culture
• Produce disease in susceptible host
• Re-isolate original microbe
http://www.nsc.gov.tw/files/popsc/2003_276/9208-13-04.jpg