Respiratory burst

• Description
  • Phagocytes (e.g., neutrophils, monocytes) ingest pathogens
  • Activation of the NADPH oxidase complex generates and releases reactive oxygen species (ROS; free radicals) that destroy the pathogens in phagosomes
• Mechanism
  • NADPH oxidase complex
    • Can generate oxygen radicals (•O2–) from O2, but also to neutralize them
    • Defective NADPH oxidase leads to chronic granulomatous disease.
  • Superoxide dismutase: generates hydrogen peroxide (H2O2) from •O2–
  • Myeloperoxidase: an enzyme in neutrophil granulocytes
    • Generates hydroxyl-halide radicals (HCl•O) from H2O2 and Cl-
    • Contains heme pigment responsible for the occasionally blue-green color of pus and sputum
  • Release of oxidative burst causes K+ influx, which triggers secretion of lysosomal enzymes into the phagosome.

Rank	ROS Species	Potency/Reactivity	Key USMLE Fact
1	Hydroxyl Radical (•OH)	Extreme	Most biologically reactive ROS; formed from H₂O₂ via the Fenton Reaction.
2	Hypochlorous Acid (HOCl)	Very High	”Bleach”; produced by myeloperoxidase in neutrophils to kill pathogens.
3	Superoxide (O₂•⁻)	Moderate	Initial ROS made by NADPH oxidase in the respiratory burst.
4	Hydrogen Peroxide (H₂O₂)	Low	Stable precursor to •OH and HOCl; can diffuse across membranes.

• Clinical significance
  • Respiratory burst is a vital component of innate immune response
  • Impaired respiratory burst leads to an elevated risk of infection with catalase-positive pathogens (e.g., Aspergillus, S. aureus).
  • Normally, phagocytes can transform H2O2 generated by invading pathogens into ROS.
  • Catalase-positive organisms can degrade their own H2O2, leaving phagocytes without substrate to convert.
  • P. aeruginosa uses pyocyanin to form ROS and eliminate competing organisms.