Micro: Pathogenesis, Part 2 Flashcards
Which exotoxins’ MOA is ADP-ribosylation?
Diptheria toxin, cholera toxin, E coli, and pertussis toxin
Which exotoxins’ MOA is superantigen production?
Toxic shock syndrome toxin, staphylococcal enterotoxin, and erythrogenic toxin.
Which exotoxins are a protease?
Tetanus toxin, botulinum toxin, lethal factor of anthrax toxin, and scalded skin toxin.
Which exotoxin is a lecithinase?
Clostridium perfringens alpha toxin
What is the pathogenic effect of ADP-ribosylation?
ADP-ribosylation modifies target proteins of the host cell causing a change of function that harms the host.
What are superantigens?
Superantigens (SAgs) are a class of antigens that cause non-specific activation of T-cells resulting in polyclonal T cell activation and massive cytokine release. SAgs can be produced by pathogenic microbes (including viruses, mycoplasma, and bacteria) as a defense mechanism against the immune system.
What is a lecithinase?
Lecithinase is a type of phospholipase that acts upon lecithin. C. perfringens alpha toxin (lecithinase) causes myonecrosis and hemolysis.
What do bacterial proteases do?
Exotoxic bacterial proteases destroy extracellular structures.
List the 4 bacteria whose exotoxins increase intracellular cyclic AMP (cAMP)
Vibrio cholerae
E. coli
Bordetella pertussis
Bacillus anthracis
Bacterial exotoxins act on which organ systems?
GI tract Nervous system Respiratory tract Skin, soft tissue, or muscle Systemic- Toxic shock syndrome toxin (S. aureus) is a superantigen that will FUCK YOU UP
Diphtheria toxin inhibits ____________ by ADP-ribosylation.
Protein synthesis
Pseudomonas aeruginosa exotoxin A inhibits __________ by ADP-ribosylation.
protein synthesis
Is there tissue or organ specificity in the effects of ADP-ribosylation of EF-2?
No.
What is the terminal result of the ADP-ribosylation of EF-2?
EF-2 is inactivated, stopping protein synthesis. Cell dies within a few hrs.
Tetanus toxin is a _____toxin.
neurotoxin
What is the gross effect of tetanus toxin?
muscle spasms and spastic paralysis due to uninhibited excitatory neurons
How does Botulinum toxin work?
neurotoxin that blocks the release of acetylcholine at the synapse, producing a flaccid paralysis.
Botulinum toxin is a ______toxin.
neurotoxin
Exotoxin A, produced by C. diff, is an enterotoxin that causes ____________.
Watery diarrhea
Exotoxin B, produced by C. diff, is a cytotoxin that damages _____________ and causes pseudomembranes to form.
colonic mucosa
Exotoxins A and B of C. diff, are glucosyltransferases that glucosylate _______________ called Rho GTPases– a process that inhibits these GTPases from performing their _____________ function.
signal transduction proteins; signal transduction function.
Glucosylation by exotoxin B of C. diff causes disaggregation of _________ filaments in the cytoskeleton, leading to apoptosis and cell death.
actin filaments
This bacterium causes gas gangrene:
C. perfringens
The alpha toxin of C. perfringens is a _________ that hydrolyzes lecithin in the cell ________, resulting in destruction of the membrane and widespread cell death.
lecithinase; cell membrane
Three exotoxins are produced by B. antharacis. Name them and briefly describe their actions.
Edema factor- causes cells to lose water/Cl-, leads to edema
lethal factor- protease that cleaves Phosphokinase req’d for cell growth. Loss of Phokinase results in failure of cell growth = cell death.
protective antigen- pokes holes in cell membrane allowing influx of edema factor & lethal factor
Describe the effect of Toxic shock syndrome toxin
Binds directly to MHC class II on surface of antigen-presenting cells. This causes release of large amounts of cytokines that produce many of the signs of toxic shock.
What causes the prominent vomiting seen in food poisoning?
Cytokines released from the lymphoid cells stimulate the enteric nervous system, which activates the vomit center in the brain.
Exfoliatin is a protease that results in scalded-skin syndrome. It is released by this bacterial species:
S. aureus
What is the target of Exfoliatin, the protease exotoxin released by S. aureus?
cleaves desmoglein, a protein in the desmosomes of skin, resulting in the detachment of the superficial layers of the skin.
Panton-Valentine (PV) leukocidin is a pore-forming exotoxin produced by ___________ strains of S. aureus.
MRSA strains of S. aureus
What does the PV leukicidin exotoxin of MRSA do?
Pokes holes in the membranes of WBCs, skin and subcutaneous tissue, through which cell contents exit into the ECM.
What toxin, produced by Strep. pyogenes, causes the rash characteristic of scarlet fever?
Erythrogenic toxin
Heat-labile enterotoxin, produced by _______ (gram - bacterium) causes watery, nonbloody diarrhea by stimulating adenylate cyclase activity in the cells of the small intestine. This results in an increased concentration of __________ that results in significant electrolyte and fluid loss into the lumen of the gut.
Enterotoxigenic E. coli (ETEC); cAMP
What are the two differences between heat labile and heat stable enterotoxins of E. coli?
1- The heat labile form can be inactivated by boiling for 30 mins. Heat stable cannot be inactivated by boiling.
2- Heat labile acts to increase cAMP, heat stable increases cGMP. Both have the same net result of water loss into gun lumen.
Shiga toxin is produced primarily by strains of _______ (bacterium).
E. coli
T/F: Shiga toxin causes bloody diarrhea
True
T/F: Heat stable/labile toxins of E. coli cause bloody diarrhea.
False
What toxin causes hemolytic-uremic syndrome (HUS)?
Shiga toxin of E. coli
The enterotoxins produced by V. cholerae and Bacillus cereus cause:
diarrhea
Pertussis toxin is produced by this bacterium:
Bor. pertussis
Pertussis toxin is the cause of this clinical presentation:
Whooping cough
T/F: Whooping cough is caused by bleeding in the respiratory tract.
False. Edema
An effect of signal transduction pathway inhibition by pertussis toxin is lymphocytosis, which causes an inability of lymphocytes to migrate to and enter lymphoid tissue (spleen, lymph nodes). Instead, there is an increase in their number:
In the blood (circulation).
T/F: Endotoxins are integral parts of the cell walls of both gram + rods and cocci.
False. Gram - rods and cocci
T/F: endotoxins are polypeptides.
False. endotoxins are lipopolysaccharides (LPS)
T/F: the enzymes producing exotoxins are usually encoded by genes on the bacterial chromosome.
False. Plasmid or bacteriophage DNA
Where are the genes that encode the enzymes that produce LPS found?
The bacterial chromosome
The toxicity of which is higher, endotoxins of exotoxins?
Exotoxins
All exotoxins produce the same generalized effects of:
fever and shock
_________ is the most important cause of septic shock, which is characterized primarily by fever, hypotension and DIC.
Endotoxin
What are the 3 critical processes by which endotoxin causes the effects of septic shock?
1- activating macrophages to produce IL-1 (fever), TNF (fever & hypotension), and nitric oxide (vasodilation = hypotension).
2- activating complement to produce C3a (hypotension & edema) and C5a (neutrophil chemotaxis).
3- activating tissue factor, an early component of the coagulation cascade (DIC).
A major site of endotoxin action is this WBC:
macrophage
The LPS:Lipopolysaccharide-binding protein complex binds to _________ (receptor) on the surface of macrophages, activating a signal cascade within the macrophage that results in synthesis of these 3 molecules of intercellular signalling:
CD14; interleukin-1, TNF, and NO
What differentiates septic shock from toxic shock?
In septic shock, bacteria are in the blood stream.
In toxic shock, toxins are in the blood stream.
In toxic shock, a blood culture would be positive or negative for bacteria?
Negative.
Why could a patient die of septic shock even after bacteria have been cleared from their blood?
The cytokines causing the symptoms are still present.
List the 5 biologic effects of endotoxin.
Fever, hypotension, DIC, inflammation, activation of macrophages
Systemic inflammatory response syndrome (SIRS) is the end result of:
The biologic effects of endotoxin
DIC manifests as:
Thousands of endovascular clots
Endotoxin-like pathophysiologic effects can occur in Gram + bacterimic infections. Since endotoxin is absent in these organisms, a different cell wall component __________, causes the release of TNF and IL-1 from macrophages.
lipoteichoic acid
Endotoxin-mediated septic shock can not be treated with antibodies to lipid A and TNF. But treatment with ______________ reduces the mortality rate of patients with sever septic shock. Explain why.
Activated Protein C.
Activated protein C functions by inhibiting thrombin formation and enhances fibrinolysis, mitigating the harmful effects of DIC that causes multiple organ failure.
**Note: Xigris, the trade name for Activated Protein C has been withdrawn from the market since 2011 due to adverse side effects (bleeding).
What two bacteria are associated with disease leading to cancer?
Helicobacter pylori and Campylobacter jejuni
How do different strains of the same species of bacteria cause different diseases?
Different virulence factors
What is a pyogenic toxin?
One that causes production of pus
What are the exotoxin mediated diseases of S. aureus?
Toxic shock syndrome, food poisoning, scalded skin syndrome
What are the pyogenic diseases of S. aureus?
skin abscess, osteomyelitis, endocarditis
What are the exotoxin mediated diseases of Strep. pyogenes?
Scarlet fever, Strep. toxic shock syndrome
What are the pyogenic diseases of Strep. pyogenes?
Pharyngitis (Strep throat), cellulitis, necrotizing fasciitis
What are the nonpyogenic (immunopathogenic) diseases of Strep. pyogenes?
Rheumatic fever, acute glomerulonephritis
What are the exotoxin mediated diseases of E. coli?
Watery, nonbloody diarrhea (HLT) Bloody diarrhea (Shiga toxin in O157:H7 strain)
What are the pyogenic mediated diseases of E. coli?
UTI (uropathic pili), Neonatal meningitis (K-1 capsule)
List the typical stages of an infectious disease and their clinical presentation:
1- incubation period (no symptoms)
2- prodrome period (generalized illness)
3- specific-illness period (more specific symptoms to disease)
4- recovery period (illness abates, pt returns to healthy state)
