Bacterial Pathogenicity: Endotoxins, Superantigens and Immune Evasion

Superantigens

• Antigens stimulate antibody/immune responses.
• Superantigens overstimulate, activating many T cells.
• This leads to a cytokine storm, causing illness, tissue damage, and septic shock.
• Can paradoxically suppress normal immune response.
• Examples:
  • Toxic shock syndrome toxin from Staphylococcus aureus.
  • Streptococcus pyogenes.
• T cells: involved in cell-mediated immunity.
• Cytokines: messaging molecules.

Toxic Shock Criteria

• Temperature > 38.9^\circ C.
• Systolic blood pressure < 90 mm Hg.
• Rash with desquamation (skin peeling).
• Involvement of at least three organ systems (kidneys, lungs, heart, liver).

Endotoxins

• Found in the lipopolysaccharide layer of Gram-negative bacteria.
• Released upon bacterial death and breakdown.
• Small amounts released during infection; more released as bacteria die (e.g., during phagocytosis or antibiotic treatment).
• Antibiotics can initially worsen symptoms due to increased lipopolysaccharide release.
• Signs and symptoms:
  • Similar across different endotoxins.
  • Fever.
  • Toxic shock.
  • Immune system involvement.

Fever Induction

• Endotoxins stimulate release of pyrogens from phagocytes.
• Pyrogens act on the temperature regulating center in the brain, resetting body temperature higher.

Other Responses

• Muscle weakness.
• Generalized aches and pains.
• Diarrhea.
• Malaise (feeling unwell).
• Severe cases can result in septic shock.

Septic Shock from Endotoxins

• Endotoxins induce cytokine release.
• Cytokines damage blood capillaries, causing leakage.
• Fluid leaks into tissues, contributing to shock.

Exotoxins vs. Endotoxins

Bacterial Evasion of the Immune System

• Blocking or avoiding phagocytosis.
• Preventing phagocytes from moving towards them.
• Preventing engulfment by phagocytes.
• Hiding in immune-privileged sites (e.g., central nervous system).

Summary of Bacterial Pathogenicity

• Disease is a balance between health and pathogenic factors.
• Infections can be:
  • Endogenous (from within).
  • Exogenous (from outside).
• Disease depends on bacterial pathogenicity/virulence:
  • Infective dose.
  • Ability to adhere (pili, slime layers, biofilms).
  • Toxins (endo- and exotoxins).

Toxin Effects

• Exotoxins:
  • Cause cell rupture or interfere with cell function.
  • Interfere with nerve function.
  • Act as superantigens.
  • Treatable with toxoids and antitoxins.
• Endotoxins:
  • Lipopolysaccharides from cell walls.
  • Create fever and potentially septic shock.