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60 Cards in this Set

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What are the two mechanisms leading to cell death?
cell lysis and programmed cell death
What are the three ways lysis of host cells occurs?
1. Microorganisms produce toxins that affect the integrity of the cell membrane
2. Microorganism multiplies within the host cell, leading to cell lysis.
3. Infected cells are eradicated by killer lymphocytes as the result of cell-mediated immunity.
In this disease, membrane-damaging toxins produced by one of the anaerobic clostridia lyse red blood cells.
gas gangrene
This disease is characterized by the skin rash produced when endothelial cells of small vessels are killed by the intracellular growth of the infecting rickettsiae.
Rocky Mountain spotted fever (RMSF)
Programmed cell death which is a part of the normal mammalian cell cycle.
apoptosis
Give two examples of viruses that may stimulate cells to undergo premature apoptosis.
HSV and HIV
Give an example of a virus that blocks apoptosis and thereby immortalizes the host cell.
Epstein-Barr virus
Give four examples of diseases that produce toxins that alter a key aspect of metabolism in ways that resemble the action of hormones or other pharmacological effectors.
1. tetanus
2. botulism
3. cholera
4. whooping cough
This disease is characterized by swelling of limbs or the scrotum due to filariae becoming lodged in lymphatics.
elephantiasis
The host response to infection is often owing to what two responses?
inflammation and the immune response
Give four examples of host responses to infection that lead to harmful outcomes for the host:
1. The accentuated inflammatory response that places patients with a brain abscess at risk of dying
2. The overwhelming activation of the complement system that kills patients suffering from septicemia
3. An autoimmune response that causes rheumatic fever
4. Cell-mediated immunity responsible for manifestations of chronic tuberculosis
T/F Toxins play an important role in diseases caused by fungi, protozoa and worms.
False. Toxins are characteristics unique to pathologic bacteria.
These toxins modulate intracellular targets (2)
exotoxins and type III cytotoxins
These toxins act on the cell surface (3)
endotoxin, membrane-damaging toxins and superantigens
These toxins modulate targets in the extracellular matrix (1)
exoenzymes
This type of secretion system is an autotransport system built into the toxin.
type I
This type of secretion system is based on an apparatus within the bacterial cell membrane which transports toxins out of the bacterial cell.
type II
What four questions help determine whether the toxin is important in the infectious process?
1. Does the toxin alone, in purified form, damage the host, using animals or cultured cells as experimental hosts?
2. Is virulence quantitatively correlated with toxin production?
3. Can a specific antibody (antitoxin) prevent or alleviate the manifestations of the disease?
4. If toxin production is impaired in the pathogen, is the disease process affected?
Genes that encode toxins are frequently contained within DNA elements such as:
plasmids and temperate bacteriophages. The locations of these genes on mobile DNA molecules ensure that the ability to produce toxin can rapidly spread to nontoxigenic bacteria.
T/F All toxins are produced continuously throughout the life cycle of the bacteria.
False. Some toxins are produced continuously by growing bacteria; others are synthesized when the bacteria enter the stationary phase.
Give some examples of spore-forming bacteria that make potent exotoxins (4).
Organisms that cause botulism, gas gangrene, and tetanus from the genus Clostridium, and the organisms that cause anthrax, of the genus Bacillus.
T/F Bacterial toxins work at very low concentrations
True.
What is the function of the A and B domains of exotoxins?
The B domain binds to the cell membrane and delivers the A domain into the host cell.
Which domain possesses enzymatic activity that is specific for each toxin?
A domain
What enzymatic reaction is characterized by diphtheria toxin, cholera toxin, and exotoxin A of Pseudomonas aeruginosa?
ADP ribosylation
Diphtheria toxin
AB
cholera toxin
A:5B
anthrax toxin
2A:B
A1 is an adenylate cyclase (termed the edema factor), and A2 is a protease (termed the lethal factor).
Exotoxins are synthesized as protoxins. Activation usually involves what two steps?
Proteolytic cleavage and reduction of a disulfide bond that often holds the A and B domains together.
During this process, the A domain is translocated across the cell membrane and into the intracellular compartment of the host cell.
receptor-mediated endocytosis
Give two examples of zinc proteases (neurotoxins).
botulinum and tetanus toxins
The diphtheria toxin inhibits cell physiology by blocking what?
host cell protein synthesis
What three functions does the B domain contribute to the delivery of the A domain into the cytosol with the diphtheria toxin?
1. receptor binding
2. transport into the endosome
3. translocation function for the A domain into the cytosol
This substrate for diphtheria toxin is a factor in eukaryotic protein synthesis that catalyzes the hydrolysis of GTP required for the movement of ribosomes on messenger RNA.
elongation factor 2 (EF-2)
What is the MOA for diphtheria toxin with respect to EF-2?
ADP ribosylation inactivates EF-2 and kills cells by irreversibly blocking protein synthesis.
What is the MOA of cholera toxin?
ADP ribosylation of G proteins that promotes the "active" form and therefore elevates intracellular synthesis of cAMP which provokes the movement of massive quantities of fluid across the intestinal membrane and into the lumen of the gut.
What is the target tissue for cholera toxin?
small intestinal epithelium
What is the target of ADP ribosylation by cholera toxin?
G protein
This neurotoxin inhibits the release of stimulatory neurotransmitters, resulting in flaccid paralysis.
botulinum toxin
This neurotoxin migrates up the axon, across the interneuronal junction, and into the internal neuron, where its A domain inactivates vesicle fusion at the interneuronal junction to inhibit the release of inhibitory neurotransmittters, resulting in spastic paralysis.
tetanus toxin
Type III cytotoxins are released directly into the host cell by a contact-dependent mechanism when the bacterium directly contacts the host cell. Give 5 examples of bacteria that use type III cytotoxins.
Salmonella, Shigella, Pseudomonas, the cholera bacilli, and the plague bacilli.
List the two main MOA of type III cytotoxins.
cell killing and modulation of the actin cytoskeleton
List 4 alarm reactions elicited by low concentrations of LPS:
1. fever
2. activation of complement by the alternative pathway
3. activation of macrophages
4. stimulation of B lymphocytes
Why is the term endotoxin misleading?
It is not internalized, and it exerts a toxic effect only at high concentrations.
What are pattern recognition receptors?
Early activation of our innate immune system by pattern recognition receptors provide us with a rapid and effective response to infection and is the catalyst for activating our adaptive immune system, which is responsible for long-term resistance to infection. Examples include endotoxin, lipoteichoic acid, lipoglycans and mannans.
Of the three parts of LPS, what is the biologically active component?
Lipid A
The primary targets for endotoxin possess specific receptors called toll-like receptors. Give 4 examples of the primary target cells for endotoxin.
1. macrophages
2. neutrophils
3. platelets
4. B lymphocytes
Name the two major cytokines released after encounter with endotoxin.
interleukin-1 and tumor necrosis factor
Endotoxin activates complement by which pathway?
alternative
What three affects on macrophages does endotoxin have?
1. increased production of lysosomal enzymes
2. enhanced rate of phagocytosis
3. secretion of hydrolases
By inducing the release of IL-1, endotoxin induces B lymphocytes (but not T lymphocytes) to do what?
divide
The deposition of thrombi in small vessels, with consequent damage to the areas deprived of blood supply.
disseminated intravascular coagulation (DIC)
Waterhouse-Friderichsen syndrome
Adrenal insufficiency due to infarction leading to rapid death, found in some cases of meningococcal infection.
What 3 ways does endotoxin contribute to coagulation?
1. activation of factor XII to set off the intrinsic pathway
2. platelets release the contents of their granules, which are involved in clotting
3. neutrophils release proteins known to stabilize fibrin clots
Name the lipase toxin produced by the clostridium of gas gangrene.
lecithinase
Alpha toxin of Staphylococcus aureus is an example of what?
a homogeneous pore forming toxin
The prototype heterogeneous pore-forming toxin.
streptolysin O
Where is the location of action of exoenzymes?
extracellular matrix
Chemically inactivated toxins used to vaccinate against several diseases.
toxoids
These type of toxins, which modulate intracellular targets, are secreted by a contact-dependent mechanism.
Type III cytotoxins