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
Describe the steps of pathogenesis.
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
How do you calculate virulence of a pathogen?
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
Describe the specific mechanisms of adherence and some examples.
- Capsule/slime layer-E. coli, Strep. mutans-promote adherence
- Adherence proteins-Strep. pyogenes, Neisseria gonorrhoeae-bind to receptors
- Lipoteichoic acid-Strep pyogenies-bind to respiratory mucosal receptor
- Fimbrieae (pili)-Neisseria gonorrhoea, Salmonella, pathogenic E. coli-bind to epithelium
Compare and contrast bacteremia and septicemia.
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
Define enterotoxins.
Subclass of exotoxins. Affect small intestine and cause secretion of fluid into intestinal lumen, leads to vomiting and diarrhea
Describe the three different types of exotoxins, their mechanisms, and examples.
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
Describe the mechanism of diptheria toxin.
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
Describe the mechanism of cholera toxin.
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
How does vibrio cholera use quorum sensing to increase its spread?
- when there are is a high cell count, shed out/
- low cell count-increase virulence factors for toxicity
Describe the differences between exotoxins and endotoxins?
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
What (6) host factors put someone more at risk for disease?
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
What innate immune defense protect us?
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
What is nosocomial infection?
infection contracted in a healthcare setting
Neisseria gonorrhea- Describe mechanism of adherence
1) opa (opacity associated) protein on cell binds to CD66 receptors on epithelium
2) pili facilitate binding to epithelium
Streptomycces pyogenes- Describe mechanisms of adherence
1) M protein on the cell binds to receptors on respiratory mucosa
2) lipoteichoic acid also facilitates binding to resp mucosal receptor