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Mechanisms of microbial disease

Mechanisms of microbial disease. Schaechter et al, Chapter 9 Burton & Engelkirk Chapter 7. Microbe is Extracellular. Microbe secretes exotoxin Botulinus, tetanus toxin (neurotoxins) Enterotoxins (Cholera toxin, toxigenic E, coli, stimulate adenylate cyclase; Shigella toxin, cytotoxic;

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Mechanisms of microbial disease

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  1. Mechanisms of microbial disease Schaechter et al, Chapter 9 Burton & Engelkirk Chapter 7

  2. Microbe is Extracellular • Microbe secretes exotoxin • Botulinus, tetanus toxin (neurotoxins) • Enterotoxins (Cholera toxin, toxigenic E, coli, stimulate adenylate cyclase; Shigella toxin, cytotoxic; E. coli O157:H7, both) • Hemolysin, leukocidin, lecithinase • Microbe secretes enzymes • Coagulase, kinases (fibrinolysin), hyaluronidase, collagenase • Microbial membrane elicits reaction • Endotoxin, the lipopolysaccharide of the outer membrane of Gram-negative bacteria

  3. Functional Damage • Biochemical changes in host cell • Ion leakage, fluid leakage • Cholera toxin, targets intestinal epithelia • Lytic pores, S. aureusα-toxin • Disruption/destruction of membrane • Inhibition of protein synthesis • Diphtheria, Pseudomonas aeruginosa • Inhibition of nerve function • Clostridium toxins, tetanus, botulinum

  4. Microbe is Extracellular • Microbe secretes exotoxin • Botulinus, tetanus toxin (neurotoxins) • Enterotoxins (Cholera toxin, toxigenic E, coli, stimulate adenylate cyclase; Shigella toxin, cytotoxic; E. coli O157:H7, both) • Hemolysin, leukocidin, lecithinase • Microbe secretes enzymes • Coagulase, kinases (fibrinolysin), hyaluronidase, collagenase • Microbial membrane elicits reaction • Endotoxin, the lipopolysaccharide of the outer membrane of Gram-negative bacteria

  5. Functional Damage • Biochemical changes in host cell • Ion leakage, fluid leakage • Cholera toxin, targets intestinal epithelia • Lytic pores, S. aureusα-toxin • Disruption/destruction of membrane • Inhibition of protein synthesis • Diphtheria, Pseudomonas aeruginosa • Inhibition of nerve function • Clostridium toxins, tetanus, botulinum

  6. Microbe invades cell • Cell membrane weakened by enzymes • Fimbriae/pili allow attachment to cell wall – confers specificity for cell types

  7. Microbe invades cell • Cell membrane weakened by enzymes • Fimbriae/pili allow attachment to cell wall – confers specificity for cell types

  8. Intracellular • Host cell killed: • Lysis during replication • Necrosis • Apoptosis • Immune system attacks infected cells

  9. The cell cycle Apoptosis, programmed cell death A G1 G0 S M G2 Mitosis (Cell division)

  10. APOPTOSIS In response to defined signals Follows defined sequence of events “Orderly shut-down” of cell functions Cell macromolecules recovered, recycled NECROSIS In response to non-specific damage Often starts with membrane destruction, events thereafter unpredictable Disorderly No recovery of contents Apoptosis vs necrosis

  11. Different cell types • Connective tissue, fibroblasts • Endothelial cells, lining of blood vessels • Epithelial cells, “outside” of several tissues • Hepatocytes, liver cells • Some cell populations are continually being renewed (turnover), others are “permanent”

  12. Rat fibroblasts

  13. Renewal by duplication - proliferation eg endothelial cells pancreas hepatocytes ? Renewal by differentiation of stem cells eg skin, intestinal wall, blood cells Cell renewal

  14. Cell reproduction, cell development “Generic” Specialized Stem cells Differentiated cells Pluripotent stem cells Different types of differentiated cells Totipotent (embryonic) stem cells Organs, organisms ?

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