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36 Cards in this Set
- Front
- Back
What is the definition of microbial toxins
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Macromolecular products of microbes that harm susceptible animals, usually by altering cellular structure or function. They are very potent
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What are some important things to remember about toxins
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Some toxins cause specific clinical manifestations; Other toxins contribute to pathogenesis without causing unique signs and symptoms; Toxin-mediated diseases cause significant morbidity and mortality; Certain toxins have the potential to be used as agents of bioterrorism
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Where in bacteria are genes for toxin production often present
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Mobile genetic elements, such as bacteriophages, plasmids or transposons
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Genes for toxins and other virulence factors in pathogenic microbes are often coordinately regulated by what
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Environmental signals. Microbes can use two-component regulatory systems to detect when they are in an animal host and express virulence factors appropriate for growth in host
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What are the composition and properties of toxins
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Most bacterial toxins are proteins. They are heat labile, immunogenic, and neutralized by specific antibodies
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What are the mechanisms of action in toxins
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Facilitate spread through tissue; damage cellular membranes; Stimulate production of excessive amounts of cytokines; Inhibit protein synthesis; Activate second messenger pathways; inhibit release of neurotransmitters; modify cytoskeleton of target cell
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What are hyaluronidase, collagenase, elastase, deoxyribonuclease, and streptokinase
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Toxic enzymes that break down the extracellular matrix or degrade cellular debris in necrotic tissue
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What are membrane-damaging toxins sometimes called
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Hemolysins, because they lyse erythrocytes; however, they are usually active against other cell types and are more accurately designated as cytolysins
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What do lecithinases do
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Degrade essential components of cell membranes
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What are pyrogenic exotoxins? Name three
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Family of related proteins that includes the erythrogenic toxins of Streptococcus pyogenes, the enterotoxins of Staphylococcus aureus, and toxic shock syndrome toxin of S. aureus.
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Pyrogenic exotoxins are involved in pathogenesis of what
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Scarlet fever, food poisoning, and toxic shock syndrome
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Why are pyrogenic exotoxins designated as superantigens
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They can activate populations of T cells that are specific for many different antigens. They are the most potent known activators of T cells
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Besides activating T cells, what else do superantigens do
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They enhance susceptibility to LPS, suppress B cell mediated responses, and stimulate cytokine production by macrophages
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How do pyrogenic exotoxins work
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They bind to MHC class II on APCs, which then bind to specific V chains on T cells at a site distant from the T cell receptor. This stimulates production of excessive amounts of cytokines (IL-2, IFN-gamma)
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What is the mechanism of action of Diphtheria toxin and Pseudomonas aeruginosa exotoxin A
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They inactivate elongation factor 2 (EF-2), which is required for peptide chain elongation.
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What are Diphtheria toxin and Pseudomonas aeruginosa exotoxin A
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ADP ribosyltransferases that transfer adenosine diphosphate ribose from NAD to EF-2, inactivating it
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What are Shiga toxins of Shigella dysenteria and E. coli and the plant toxin ricin
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Highly specific RNA N-glycosidases that remove one particular adenine residue from the 28S RNA of the 60S ribosomal subunit
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Define cytotonic
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Toxins that alter the functions of target cells without killing them
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What are heat-labile enterotoxins of Vibrio cholerae and E. coli
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ADP ribosyltransferases that activate cell membrane-associated adenylate cyclase by ADP-ribosylating the Gs protein of the cyclase complex. This increases intracellular cAMP in enterocytes and causes secretory diarrhea
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What is pertussis toxin
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An ADP-riboslytransferase that activates adenylate cyclase by deactivating inhibitory G protein of the cyclase complex.
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What does heat-stable enterotoxin I (ST-I) of E. coli do
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Activates guanylate cyclase, increasing intracellular cGMP in enterocytes and causing diarrhea
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What are the anthrax edema factor component of anthrax toxin and the toxin of Bordella pertussis
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Adenylate cyclase enzymes that enter target cells and increase intracellular cAMP. Activated by calmodulin and calcium in target cells
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How does Botulinun toxin work
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Causes flaccid paralysis by inhibiting release of acetylcholine at myoneural junctions
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How does tetanus toxin work
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Inhibits release of neurotransmiter from inhibitory interneurons in the spinal cord, resulting in muscular contraction and tetany
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What is the mechanism of action of Botulinum toxin and tetanus toxin
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They have zinc-dependent endopeptidases that recognize specific proteins of the neuroexocytosis apparatus and cleave them at particular sites
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What does Clostridium difficile cytotoxin (toxin B) do
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Causes disaggregation of actin filaments by glucosylating RhoA, one of the small GTP-binding proteins
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What are the characteristics of toxins that act extracellularly or on plasma membranes
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They are diverse in structure and functions. Their specificity is usually determined directly by the target of their action
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What are the characteristics of toxins that have intracellular targets
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They are usually bifunctional proteins; Normal membrane constituents are used by toxins as receptors; Susceptibility or resistance is often determined by the presence or absence of specific receptors; Toxins usually enter by endocytosis
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What is the receptor for diphtheria toxin
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The heparin-binding EGF-like growth factor precursor
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What is the receptor for cholera toxin and related heat-labile enterotoxins
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Ganglioside GM1
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What is the membrane receptor for Shiga toxins of Shigella dysenteriae and E. coli
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Glycolipid Gb3
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How do Shiga toxin, exotoxin A, cholera toxin, and pertussis toxin enter the cytosol
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They follow an endocytic pathway through the trans-Golgi network and endoplasmic reticulum
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What are some of the ADP-ribosylating toxins
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Heat-labile enterotoxins, pertussis toxin, diphtheria toxin, exotoxin A of P. aeruginosa. They all catalyze transfer of ADP-ribose from NAD to acceptor proteins
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What are some of the principles of Prophylaxis and therapy of toxin-mediated disease
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Antitoxic antibodies neutralize specific toxins and prevent their toxic effects; Toxoids retain immunogenicity but lack toxicity; Passive immunization involves administration of antibodies; Active immunization involves administration of an antigen; a primary series of immunization and periodic booster doses are required to achieve protective levels
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What is used to immunize children against tetanus, diphtheria and pertussis
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Tetanus and diphtheria toxoids combined with acellular Bordetella pertussis vaccine
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What are immunotoxins
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Hybrid molecules that contain the active A fragment of toxin fused with specific ligands. They are designed to kill tumor cells that display specific receptors
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