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. aureus α-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. aureus α-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

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

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

11. Apoptosis vs necrosis 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

12. Inflammation
Response of organism to infection/toxic insult. Destruction/healing
Acute: Vasodilation (histamines, bradykinin) > Redness, Swelling – influx of fluid (plasma). White blood cells esp. neutrophils, macrophages, and cytokines leaking into tissue/cells > actication of coagulation and fibrinolysis cascades, comlement system > attack bacterial cell walls,
Itching/irritation – histamines released by mast cells
Chronic: persistence of eg macrophages, neutrophils releasing reactive oxygen species
Atherosclerosis, arthritis

13. 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”

14. Rat fibroblasts

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

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