Microbial Toxins Flashcards
Other toxins contribute to pathogenesis w/o causing unique signs or symptoms, such as ____.
pneumolysin
What are superantigens?
most potent known T cell activators; bind MHC class II on different sites from antigen binding sites and stimulate cytokine production
How do heat-labile enterotoxins, like V. cholerae and E. coli, work?
activate adenylate cyclase by stimulating the Gs regulatory protein; causes increased cAMP in small intestines leads to active Cl secretion and secretory diarrhea
How do toxins damage cell membranes?
kill target cells using hemolysins/cytolysins that form pores; lecithinases degrade specific cell membrane components and disrupt membrane integrity
What are the most toxic biological substances known?
clostridial neurotoxins (botulinum and tetanus)
Toxins cause the major manifestations of disease in? (8)
botulism, cholera, diphtheria, whooping cough, scalded skin syndrome, scarlet fever, tetanus, TSS
How do toxins inhibit protein synthesis?
irreversibly, causing death
How do toxins get into the cell?
via endocytosis
High doses of LPS cause ____ and _____ and is usually mediated by _____.
shock, DIC; cytokines
What are bacterial protein toxins?
exotoxin- heat labile, immunogenic, and neutralized by antibodies
Name 2 bacterial protein toxins.
- diphtheria toxin 2. botulinum toxin
What is active immunization?
admin of a toxoid to a patient in order to elicit production of specific anti-toxic antibodies
How does C. diff work?
it’s toxins A and B are glucosyl transferases that alter the actin cytoskeleton by transferring glucose from UDP-glucose to Rho GTPase, inactivating it
How does Pertussis toxin work?
it’s an ADP ribotransferase that increases adenylate cyclase activity by inhibiting the inhibitory G1 regulatory protein, causing increased cAMP
Susceptibility to toxins actin on the plasma membrane is determined by presence or absence of _____.
normal receptors on target cells
Tetanus and Botulium toxin are _____-dependent _____ that inactivate specific _____ proteins required for neuroexocytosis.
zinc; endopeptidases; SNARE
What is a toxoid?
derivatives of toxins that retain immunogenicity but lack toxicity
What is endotoxin?
LPS of gram-negative bacteria
What toxins stimulate cytokine production?
pyrogenic exotoxins (Strep. pyogenes, Staph. aureus); superantigens
Which toxins inhibit protein synthesis?
Diptheria, psuedomonas aeruginoa exotoxin A, shiga toxin from Shigella dysenteriae and E. coi
Toxins acting on the plasma membrane are _____ proteins with separate binding domains, A (for ____) and B (for ____).
bi-functional; active; binding
What does Heat-Stable enterotoxin I of E.coli do?
increases cGMP, leading to secretory diarrhea
How do antitoxins work?
antibodies bind to toxins and prevent their toxicity
How does Tetanus toxin inhibit NT release?
inhibits NT release from interneurons in the spinal cord, causing spastic paralysis
Name 2 toxins that can inhibit the release of neurotransmitters.
- Botulinum 2. tetanus
What is an immunotoxin?
toxin fragment without its receptor + new ligand
Name 6 major actions of bacterial toxins.
- facilitate spread of microbes through tissues 2. damage cell membranes 3. stimulate cytokine production 4. inhibit protein synthesis 5. modify intracellular signaling pathways 6. inhibit release of neurotransmitters
How does Anthrax Lethal Factor (LF) work?
its an endopeptidase that cleaves MAP kinase signal proteins to inactivate them, and somehow this is lethal.
What is passive immunization?
giving antibodies to provide immediate but temporary protection against a toxin or infectious agent
Which toxins modify intracellular signaling pathways?
Vibrio cholerae, E. coli, Bacillis anthracis, Bordatella pertussis, Clost. difficile
Which antigenic types of Botulinum cause disease in humans?
A, B, E
How do toxins facilitate spreading of microbes thru tissues?
break down the ECM or degrade necrotic tissue using hyaluronidase, collagenase, elastase, deoxyribonuclease, or streptokinase
How does Botulinum toxin inhibit NT release?
inhibits the release of ACh at the myoneuronal junctions, causing flaccid paralysis
How does Anthrax Edema Factor (EF) work?
B. anthracis and B.pertussus are adenylate cyclases that cause intracellular cAMP to increase, causing edema
What is the molecular version of Koch’s postulates?
- show that the phenotype of disease is assoc. with the pathogenic microbe 2. show inactivation of the gene causes decreased virulence 3. replacing the mutated gene with wildtype restores virulence
What happens once the toxin gets into the cell?
the active portion has to be translocated to its target in the cytosol
What is the traditional method of showing a specific toxin has a role in pathogenesis??
- show that purified toxin has the same s/s as infection by the microbe 2. show antitoxin prevents the disease 3. show that virulence correlates with the amount of toxin produced 4. Show that mutants are avirulent and virulence can be restored if toxin is produced again
LPS is an example of a ____, recognized by the immune system to illicit an immune response.
PAMP
Low doses of LPS activates _____, _____, and _____ to cause ____, _____, _____, and _____.
macs, B cells, alt. complement; fever, acute phase reactants, antibody synthesis, and inflammation
