L17-Pathogenesis/Virulence (27.6-27.12) 826-840 Flashcards

http://vimeo.com/21661441 CWN Speaker Series: Dr. Rita Colwell, 2010 Stockholm Water Prize Winner

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1
Q

Describe the steps of pathogenesis.

A

1-Exposure-to pathogens
2-Adherence-to skin or mucosa
3-Invasion-through epithelium
4-Colonization/Growth-Production of Virulence Factors
5-Toxicity or Invasiveness-(toxin effects are local or systemic) or (further growth at original and distance sites
6-Tissue damage, disease

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2
Q

How do you calculate virulence of a pathogen?

A

Determine the LD50/lethal dose 50 or the dose of an agent that kills 50% of the animals in a test group. High virulence=Strep. pneumonia ~50 cells/mouse, Salmonella enterica ~5000 cells/mouse

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3
Q

Describe the specific mechanisms of adherence and some examples.

A
  1. Capsule/slime layer-E. coli, Strep. mutans-promote adherence
  2. Adherence proteins-Strep. pyogenes, Neisseria gonorrhoeae-bind to receptors
  3. Lipoteichoic acid-Strep pyogenies-bind to respiratory mucosal receptor
  4. Fimbrieae (pili)-Neisseria gonorrhoea, Salmonella, pathogenic E. coli-bind to epithelium
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4
Q

Compare and contrast bacteremia and septicemia.

A

b-presence of bacteria in bloodstream, may or may not cause symptoms, can progress to septicemia
s-rapid spread of pathogen through blood and lymph, replicating, can cause inflammation, septic shock and even death

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5
Q

Define enterotoxins.

A

Subclass of exotoxins. Affect small intestine and cause secretion of fluid into intestinal lumen, leads to vomiting and diarrhea

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6
Q

Describe the three different types of exotoxins, their mechanisms, and examples.

A

1) cytolytic-degrade cell membrane via attack of sterol or phospholipid, lyses cells. Ex. hemolysins, alpha-toxin of Clostridium perfringen or Staph
2) AB-B-binds to host receptor cell while A migrates across cell membrane. Ex diptheria/cholera toxin, neurotoxins of Clos. tetani/botulinum
3) Superantigens-stimulate large number of immune cells. Ex. nonspecific binding of MHC II with T cell receptors by Strep pyogenes or Stph aureus

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7
Q

Describe the mechanism of diptheria toxin.

A

1) secreted by Corynebacterium diptheriae as a single polypeptide
2) frag B binds to host cell receptor (heparin binding epidermal growth factor)
3) proteolytic cleavage
4) frag A enters cell, blocks transfer of AA from tRNA to growing polypeptide chain

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8
Q

Describe the mechanism of cholera toxin.

A

1) cholera travels to intestine, secrete AB toxin
2) B frag binds to glycolipid on CM of intest epithelial cells
3) A frag cross membrane and activates adenylate cyclase (ATP -> cAMP)
4) incr cAMP induces secretion of Cl- and H2CO3 into lumen
5) change in [ion], secretion of large amounts of water

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9
Q

How does vibrio cholera use quorum sensing to increase its spread?

A
  • when there are is a high cell count, shed out/

- low cell count-increase virulence factors for toxicity

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10
Q

Describe the differences between exotoxins and endotoxins?

A

EXO-proteins excreted from pathogen cell as it grows; specific-binds to spec receptor or structure; high toxicity, highly immunogenic/neutralizing antibody; toxoid potential, does not produce fever
ENDO-lipopolysaccharides LPS as part of the outer layer of cell membrane (released on lysis of gram - bac); general mode of action causes diarrhea, vomiting; weakly toxic/rarely fatal; poor immunogen/no response for neutralization; no toxoid potential, often induces fever in host

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11
Q

What (6) host factors put someone more at risk for disease?

A

1) already sick/immunocompromised
2) autoimmune diseases
3) hospital acquired infections
4) age-infant, over 65
5) diet-low protein, calories
6) stress-fatigue, exercise, dehydration, climate change

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12
Q

What innate immune defense protect us?

A

1) natural host resistance-different species have different susceptibilites to particular pathogen
2) pathogens must adhere and colonize at site of exposure, must be compatible with nutritional and metabolic needs
3) physical chemical barriers-.lysozyme, removal of particles in nospharynxmucus, cilia lining trachea, skin, mucus and phagocytes in lunges, blood and lymph inhibit, rapid pH change in stomach, normal flora compete, flushing of urinary tract

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13
Q

What is nosocomial infection?

A

infection contracted in a healthcare setting

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14
Q

Neisseria gonorrhea- Describe mechanism of adherence

A

1) opa (opacity associated) protein on cell binds to CD66 receptors on epithelium
2) pili facilitate binding to epithelium

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15
Q

Streptomycces pyogenes- Describe mechanisms of adherence

A

1) M protein on the cell binds to receptors on respiratory mucosa
2) lipoteichoic acid also facilitates binding to resp mucosal receptor

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16
Q

Influenza– Describe mechanism of adherence

A

usually targets avian lung mucosal cells. the glycoprotein humagglutinin mutates and can adhere to other respiratory mucosal cells