Bacterial & Viral Evasion of Host Immune System: Mechanisms & Examples

Posted on Aug 27, 2024 in Biology

Bacterial and Viral Evasion of the Immune System

Mechanisms of Immune Evasion

Influencing the Complement System

  • Encoding proteins homologous to host complement regulatory proteins
  • Viruses: Hijacking or co-opting the complement defense system
  • Bacteria: Inhibiting complement activation
  • Proteases that degrade complement components

Inducing Immunosuppression

  • Producing toxins (e.g., Staphylococcus enterotoxins)
  • Viral replication affecting lymphocyte function, leading to immunosuppression
  • Soluble factors released from infected cells
  • Viral triggering of imbalances in immune regulation, leading to overactivity of suppressor cells
  • Trauma, burns, or surgery

Influencing Lymphocytes

  • Directly activating or suppressing lymphocyte activity
  • Infecting lymphocytes, preventing an adequate immune response
  • Generating cytotoxic T-lymphocytes, suppressor cells, and interferon production

Influencing Phagocytosis

  • Avoiding phagocytosis by blocking certain steps
  • Remaining in areas inaccessible to phagocytes
  • Not triggering an inflammatory response
  • Inhibiting phagocyte chemotaxis
  • Covering themselves with “self” components to hide
  • Surviving inside phagocytic cells

Bacterial Damage via Endotoxin & Exotoxin

Endotoxin

  • Not actively secreted, but a component of the cell wall
  • Found in Gram-negative bacteria only (lipopolysaccharide)
  • Toxic only at high levels
  • Released when bacteria die and the cell wall lyses
  • Receptors: Macrophages, lymphocytes, and other cells
Mechanism of Action (MOA)
  • Host cell receptors (TLRs) bind to pathogen components
  • Cytokine release (IL-1, IL-6, TNF)
  • Cytokines stimulate the hypothalamus to produce prostaglandins
Clinical Manifestations
  • Increased white blood cell count
  • Fever
  • Hypotension
  • Shock

Exotoxin

  • Secreted from living bacteria
  • Work by altering host cell metabolism
  • Different toxins have different MOAs
Classifications
  • Site and features of intoxication (cytotoxin, neurotoxin, enterotoxin)
  • Structure (e.g., AB subunit toxins)
  • Heat-labile vs. heat-stable
  • Host cell target and mechanism of action
Examples of Exotoxins and their Effects
Type I: Cell Surface Active
  • Superantigens:
    • Staphylococcus aureus –> Toxic Shock Syndrome
    • Bridge MHC class II proteins on antigen-presenting cells (APCs) with T cell receptors
    • Result in non-specific T cell activation and massive cytokine release
  • Heat-Stable Enterotoxins:
    • E. coli, withstands 100°C heat
    • Binds to membrane guanylate cyclase, leading to cyclic GMP activation
    • Causes loss of water and electrolytes from cells
Type II: Pore-Forming
  • Cholesterol-Dependent Cytolysins (CDCs):
    • Require cholesterol in the host cell membrane
    • Form pores 25-30 nm in diameter
    • Secreted via Type II secretion system
    • Exception: Pneumolysin (Streptococcus pneumoniae)
    • Modify histones and dysregulate protein expression, leading to inflammation
  • RTX Toxins:
    • Contain a repeating 9-amino acid residue motif
    • Example: E. coli hemolysin A
Type III: Intracellular-Acting
  • Act inside the host cell cytoplasm
  • Modify protein components
  • Classified by mechanism of entry and action
  • Entry Mechanisms:
    • Needle-like structure for direct delivery (e.g., Yersinia)
    • AB toxins: B subunit binds to the cell, A subunit enters and modifies host proteins
  • Examples: Cholera toxin, pertussis toxin, Shiga toxin, heat-labile enterotoxin from E. coli
Specific Examples of Exotoxin Effects
  • Cytotoxins:
    • Corynebacterium diphtheriae: Inhibits protein synthesis, leading to cell death and formation of pseudomembrane
    • Streptococcus pyogenes: Damages capillaries, causing the rash of scarlet fever
  • Neurotoxins:
    • Clostridium botulinum: Blocks nerve function, causing paralysis
    • Clostridium tetani: Blocks nerve function, causing spastic paralysis
  • Enterotoxins:
    • Vibrio cholerae: Increases cAMP levels, leading to fluid loss and diarrhea

Role of Toxins in Disease

  • Direct toxicity aids in the establishment of disease
  • Interference with immune cell function

Example: Diphtheria

  • Caused by Corynebacterium diphtheriae (Gram-positive, non-spore-forming, non-motile, aerobic rod)
  • Produces an AB toxin
  • Acquired through respiratory droplets
  • Causes inflammation and damage due to circulating toxin