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62 Cards in this Set

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The plague claimed ___ deaths. What are the two forms?
> 200 million;
Bubonic - 50-75% mortality (spread by fleas)
Pneumonic - 90% mortality & highly contagious (person to person)
Does the plague still exist?
Yes as of 2003; >2000 cases worldwide (97 in the US)
How is the plague treated?
Antiobiotics; successfully treats 90% of reported cases, but R plasmids now found in some infections
Y. pestis is...
the causative agent of the plague; Gram (-) rod; ogligate parasite; 3 plasmids encode virulence factors
How do you get infected?
Flea --> Rodent --> Cat; Resevoirs are wild rodents; Humans get bit by the fleas.
How does it spread?
Fleas live/grow in 26-28 degrees; flea-specific virulence factors are made the plug the flea's digestive system, causing it to starve and bite people ferociosly. This spreads the pathogen.
Some scientists hypothesize...
the "little ice age" (1250-1850 AD) contributed to spread of the plague; warms periods contribute to its disappearance.
Plague pathogenesis
2 stages of infection, intracellular and extracellular
Plague Intracellular
The unecapsulated Y. pestis are initally engulfed by macrophages, but can still grow intracellulary. Travels to the lymph nodes, where it develops capsules.
Plague Extracellular
The lymph node (host cell) lyses and are released into the blood and travel throughout the body causing lung infections and sepsis.
Explain the Y. pestis capsule
It is formed by and F1 protein that is only produced at 37 degrees (not made in the flea). It prevents phagocytosis by PMNs (neutrophils) and macrophages. It is an adhesin for IL-1 receptors on macrophages, allowing the microbe to bind to surface of APC.
The capsule has a type III secretion system that.....
include V antigen, and it injects 6 proteins into the bound APC that causes apoptosis.
What are some other virulence factors?
plasminogen activator - a protease that inactivates complement
siderophores - bind tightly to and then transport iron into the pathogens
endo/exotoxins
Anthrax
Bacillus anthracis; ubiquitous facultative anaerobe; Gram +, endospore forming rod found in soil.
What is the infection process of anthrax?
Herbivores are infected while grazing; Carnivores are infected by either exposure directly from the soil, or exposure from infected animal.
Cases of anthrax; types of anthrax; treatment of anthrax
20,000-100,000 cases a year worldwide; Pulmonary anthrax (spore inhalation) is almost 100% mortality if not treated immediately after exposure; other forms are cutaneous or gastrointestinal (less lethal); a vaccine is available.
Pathogenesis of anthrax
Spores are taken up by the macrophages (resistant to everything an in infectious form, no spread from person to person); pathogenic strains sporulate and multiply within macrophages, develop capsules (poly-glu) then lyse cells; Encapsulated strains resist further phagocytosis and release toxins.
The anthrax toxin is comprised of...
3 plasmid encoded gene products: PA, LF, & EF
What is the process of binding for the anthrax factors?
PA (protective antigen) aggregates to get LF (lethal factor) and EF (edema factor) toxins to bind and then go into the cell.
What happens once the factors are inside the cell?
LF is a protease that inhibits major signaling pathways, including master regulator NFkB; it also kills WBCs + more cells; EF is an adenylate cyclase that elevates cAMP and causes edema
End result of anthrax
Endothelial cells become leaky causing shock & death
Anthrax as a weapon:
small particles with electrical charge to keep the endospores aloft; No person to person spread; antibiotics available, but often administered too late.
Explain the anthrax outbreaks in Russia and the US.
1979 Russia, 1 gram killed 66/77 people.
2001 US, 22 cases, 5/11 pulmonary cases died.
Usually, E. coli strains are...
enteric commensals
There are ____ known pathogenic strains of E. coli that cause ___.
200; diarrheal diseases of UTIs.
ETEC strain
Enterotoxigenic strain causes watery diarrhea via 2 plasmid-encoded enterotoxins LT & ST
EPEC
Enteropathogenic strains produce no toxins, but adhere to intestinal cells
EIEC
Enteroinvase escape phagotcytosis after being taken up, then escape and invade cells of colon.
EHEC
Enterohemorrhagic E. coli (ex: O157:H7) produce verotoxins (shiga-like and phage-encoded) that cause bloody diarrhea & kidney failure; 73,000 cases
Verotoxins
stx 1 & 2; shiga-like toxins because they were originally from shigella and then crossed over to E. coli.
Stx toxins are...
AB toxins that bind to vascular and renal epithelial cells (A inhibits protein synthesis & is an endoglycosidase)
Stx genes are carried....
on a lambda prophage
What is interesting about cows and E. coli?
Cows do not have receptors for the B component and they can have it growing in their stomach. This is what can contaminate the meat.
What is interesting about Salmonella?
There is only one species, but over 2000 strains.
Frequent carries of Salmonella
Reptiles, Chickens Eggs, Uncooked animal parts, uncooked vegetables.
Virulence factors of Salmonella
Type III secretion system that injects Sip proteins (reoragniz actin to cause cell to endocytose bounc Salmonella)
S. typhi
Cause typhoid fever; bacteria invade and then pass through intestinal wall, are phagocytosed but not killed in blood, then carried to liver, spleen and gallbladder
Carriers of typhoid fever...
Typhoid Mary - mainttain bacteria in the gall bladder and spread it.
Helicobacter pylori
responsible for most peptic ulcers; very common - 40-50% people have it worldwide, but doesn't make ulcers;
Virulence factors of H. pylori
fimbriae attach mucous-producing cells; secrete enzymes (urease) that neutralize stomach acid and produce high levels of SOD and catalase to help inhibit phagotcytic death;
Process of H. pylori
disruption mucoid covering & inflammation cause stomach acid to erode stomach lining, allowing bacteria to invade deep into tissues
Treatment for H. pylori
antibiotics
Small Pox
Variola virus; dsDNA virus; it is enveloped and has a large genome; highly contagious; stable in aerosal form for 24hrs; 10,000BC-1980; 300-500 Million died in 20th century; 50 mil cases each year with 30-50% mortality; no effective anti-virals for it;
Eradication of smallpox
effective vaccine; genome is stable & not mutating; vaccine from closely related live vaccinia virus; only a human host; obvious signs of infection; world-wide commitment to treat for it.
Smallpox as a good Bio Weapon
contagious; stable in aerosal form; genome can be synthesized;
Smallpox as a bad Bio Weapon
vaccinia gives long term immunity; infection is most contagious after visible signs, which would be pointed out;
Retroviruses
all are +RNA that contain reverse transcriptases that convert ssRNA into dsDNA as well as integrases that cause the dsDNA to integrate into the chromosome
Two types of retroviruses
Lentiviruses - are immunosuppressive (ex: HIV)
Deltaretoviruses - cause leukemia (HTLV-1)
HIV entry into host cells
your blood + infected blood; contains 2 genomes of +ssRNA, reversetranscriptase, HIV protease, tRNA primer, & integrase;
The HIV envelope...
glycoprotein 120 binds to CD4 on immune cells
chemokine receptors
macrophage = CCR5; TH cell = CXCR4; These remove gp120 bound to CD4.
What is gp41?
Gp41 is what is left after CD4 and gp120 bind to the chemokine. These bind to the CM and causes the HIV envelope to bind to the CM.
What happens after HIV binds to the CM?
RT makes DSDNA from RNA genome and integrase inserts it into chromosome of host cell.
HIV gene expression controlled by....
NFkB activation in host cell causing rounds of virion production that bud out of the cell.
How else can HIV be spread?
syncitia formation is gp41-mediated and allows cell to cell infection.
Host immune system & HIV start to...
wipe out CD4+ cells (macrophage like cell & TH cells)
Death from HIV & AIDS is from
oppurtunistic infections (viral, bacterial, & fungal)
AIDS pandemic has led to...
widespread resistance to antibiotics of many pathogens, as patients on constantly on antibiotic therapy.
HIV-1 probably arose from...
SIV found in chimps
RT makes what kind of mistakes?
1 mistake/genome making it constantly mutating/hard to cure.
Current HIV therapies
use cocktails that target 3 seperate gene products to limit formation of drug resistance (must develop resistance to all three drugs)
Total people infect with HIV; in america; in sub-saharan africa
46 million; 1 mil; 25.4 mil