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
| Feature | Exotoxins | Endotoxins |
|---|
| Source | Secreted from live microbes | Part of bacterial structure, released upon death |
| Heat Stability | Heat-labile (destroyed by heat) | Heat-stable |
| Specificity | Very specific in activity | Not particularly specific, causing generalized problems |
| Toxicity | Very toxic | Variable toxicity |
| Toxoid Potential | Can be converted into toxoids for immunization | Cannot be converted into toxoids for immunization (no vaccine potential) |
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.