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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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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;

      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


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


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


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


Microbe invades cell

  • Cell membrane weakened by enzymes

  • Fimbriae/pili allow attachment to cell wall – confers specificity for cell types


Microbe invades cell

  • Cell membrane weakened by enzymes

  • Fimbriae/pili allow attachment to cell wall – confers specificity for cell types


Intracellular

  • Host cell killed:

  • Lysis during replication

  • Necrosis

  • Apoptosis

  • Immune system attacks infected cells


The cell cycle

Apoptosis, programmed cell death

A

G1

G0

S

M

G2

Mitosis (Cell division)


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


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”


Rat fibroblasts


Renewal by duplication - proliferation

eg endothelial cells

pancreas

hepatocytes ?

Renewal by differentiation of stem cells

eg skin, intestinal wall, blood cells

Cell renewal


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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