Lectures 1-4 Flashcards
A set of criteria for determining that a newly emerging organism causes a disease.
Koch’s postulates
Is Koch’s postulates used by our doctors? Why?
No, used by scientists to identify a NEWLY emerging organism.
Characteristics of bacteria in the genus Bacillus
Long rod, Form spores, live in the soil
What are endospores? How can bacteria use it to their advantage?
Durable structures that last for decades, protect genetic material, and remain dormant until germination.
What happens once a spore germinates?
It reforms a vegetative cell which can reproduce.
What bacteria is well suited for germ warfare? Why?
Bacillus anthracis. It forms spores that can be dispersed through the air.
What are the three types of anthrax disease? (least to most lethal)
Cutaneous, intestinal, and pulmonary.
How is cutaneous anthrax obtained? Does it become systemic?
Enters through wound in skin. Usually self-limiting, becomes systemic in 5% of cases.
What is anthrax named after?
Anthracite coal
How is intestinal anthrax obtained? Symptoms? Does it become systemic?
Eating meat contaminated with B. anthracis.
Causes bloody vomiting, ulceration of intestines, and enteritis.
Systemic in 20-30% of cases.
How is pulmonary anthrax obtained? Symptoms? Does it become systemic?
Inhalation of B. anthracis spores.
1st develop flu-like symptoms, infection becomes systemic, fluid accumulates in lungs and bloody discharge occurs from body openings, death.
How long do spores remain dormant for? Can they germinate right away?
Can remain dormant in lungs for 1-2 months. Yes, some germinate right away.
What is a macrophage? What do they do?
Non-specific immune cell. Attack any pathogen/ foreign body.
What happens after the endospores are engulfed by the macrophages in the lungs?
Macrophages carry germinated bacteria to lymph nodes. Here macrophages are killed by bacterial toxins. Toxins and bacteria are then released throughout the body.
What happens once the macrophages have been killed?
They uncontrollably release their own chemicals that cause blood vessels to be overly leaky.
How do macrophages work under normal conditions?
They release their chemicals in a controlled fashion, so immune proteins can leak thru the blood vessels to the site of infection.
What does it mean when an infection is systemic?
Moves all over the body thru the blood
In pulmonary anthrax, what specifically causes a person to go into shock?
Excessive amounts of fluid leaking out of blood vessels causing blood volume to decrease.
In pulmonary anthrax, what causes the blood vessels to leak uncontrollably?
Uncontrollable release of chemicals by dead macrophages and release of edema toxin from B. anthracis.
Gets the immune system ready for the infection so it can respond quickly. Gives the immune system its first look.
Vaccine
How is a vaccine made?
Made from culture filtrates from an avirulent strain of the bacteria.
When should antibiotics be given?
Shortly after exposure, at least 24 hrs.
How long would antibiotics need to be given? Why?
At least 2 months because some spores take 60 days to germinate.
After your first exposure, your immune system produces _______________. They “remember” the organism
memory cells
Liquid that has gone through a filter
filtrate
Toxins that are secreted by bacteria
Exotoxins
What are the components of exotoxins made of? Where are these made?
Polypeptides encoded by genes. They are made inside the bacterium.
What type of exotoxin is released by B. anthracis?
AB type
What is another name for A component?
Catalytic component
What does the A component part of the toxin do?
Causes the harmful effect; has to get into the cytoplasm to do so.
What is another name for B component?
Binding component
What does the B component part of the toxin do?
Allows the toxin to bind to a receptor on the target cell so the A component/entire toxin is delivered to target cell.
In anthrax toxin, what part of the toxin enters the target cell?
the entire toxin is engulfed, the A component is then released into cytoplasm
What is the binding component that both anthrax toxins contain called?
protective antigen
How is the toxin assembled? Where does everything come from?
The individual components are secreted by bacterium, and toxin is assembled on target cell
What are the two toxins called?
lethal and edema toxin
What are the two different catalytic components?
lethal and edema factor
part of the toxin that allows it to bind to the receptor on the target cell
protective antigen
How did antibodies against PA keep the mouse from dying?
Prevented PA from binding to the target cell or prevent it from assembling to form toxin.
Highly specific proteins made by the immune system (shaped like a “y”)
Antibodies
Molecules the body sees as foreign
Antigens
How do antibodies work?
They bind to antigens acting like flags, marking the antigen for degradation by other immune cells
PA is assembled into a _____________ on the ____________ _________ on the surface of the target cell.
heptamer; cellular receptors
What happens to the little knob on the top of the PA? By what?
Cleaved off by a cellular protease.
Why is PA cleaved?
so that the catalytic components can assemble into the toxin.
Which components are released into the cytoplasm of the cell?
catalytic components
Inactivates immune cells; degrades an immune system kinase involved in chemical signaling between immune cells
lethal factor
adds a phosphate group to a protein, may activate the protein.
kinase
also kills macrophages
lethal factor
causes fluid accumulation and swelling by upsetting fluid balance in cell
edema factor
What is PA cleaved by? what is it?
furin, a membrane protease
is furin bacterial or eukaryotic in origin?
eukaryotic
Why is PA cleaved?
to exposed sites where LF or EF can bind.
Where are the toxins assembled?
on the plasma membrane of the target cell
What happens after the toxins are assembled on the target cell?
They are engulfed and a membrane bound vesicle forms around it.
What does the vesicle cause after it is formed around the toxin? and what does it do?
Causes PA to form a pore thru which the catalytic component can be released into cytoplasm
Acid causes _______ to change its shape. Why is this?
Heptamer; Because acid disrupts weak interactions like H bonds that give proteins its shape.
EF has ______ ______ activity.
adenylate cyclase
A class on enzymes that convert ATP to cyclic AMP (cAMP)
adenylate cyclases
Acts as a chemical message. Also functions in a pathway that controls water balance in cell.
cAMP
What happens when a lot of cAMP is made? What does it cause?
Water balance is upset and fluid is released causing edema.
What else caused edema associated with pulmonary anthrax?
Chemicals released by dead macrophages, causing overly leaky blood vessels.
________ ________ is an enzyme that makes ________, a messenger that causes fluid to leave the cell. It is a type of __________ __________.
Edema factor; cAMP; adenylate cyclase
Once it enters the cytoplasm, LF cleaves a ________ __________ ________. Called what?
cellular protein kinase; MAPKK
Involved in generating signals which allow immune cells to communicate
MAPKK
Lethal factor ultimately does what to the cell?
ends up killing the cell
_______ _______ degrades the cellular kinase called ________ so that immune cells cannot communicate.
lethal factor; MAPKK
What does MAPKK stand for?
mitogen associated protein kinase kinase
The suspected pathogenic organism should be present in ALL cases of the disease and absent from healthy animals.
Postulate 1
The suspected organism should be grown in pure culture
Postulate 2
A culture containing a single organism
pure culture
Cells from a pure culture of the suspected organism should cause disease in a healthy animal
postulate 3
The organism should be reisolated and shown to be the same as the original
postulate 4