U01.02.022 Respiratory burst

Respiratory burst, also known as oxidative burst, is a critical mechanism in the immune response. It involves the activation of the phagocyte NADPH oxidase complex, primarily in neutrophils and monocytes, which generates reactive oxygen species (ROS) to destroy pathogens. This process is essential for effective microbial killing and innate immunity.

Key Features

1. Mechanism

Activation of NADPH oxidase on the phagocyte membrane.
Uses O₂ as a substrate to generate superoxide (O₂⁻) and downstream ROS like hydrogen peroxide (H₂O₂) and hypochlorite (HOCl).
Requires NADPH derived from the HMP (hexose monophosphate) shunt.

2. Enzymes and Pathways

Enzyme/Component	Function
NADPH oxidase	Converts O₂ to superoxide (O₂⁻). Deficiency causes chronic granulomatous disease (CGD).
Superoxide dismutase	Converts superoxide (O₂⁻) into hydrogen peroxide (H₂O₂).
Myeloperoxidase (MPO)	Produces hypochlorite (HOCl, bleach) from H₂O₂ and chloride ions.
Glucose-6-phosphate dehydrogenase (G6PD)	Supplies NADPH via the HMP shunt. Deficiency impairs ROS generation.
Glutathione peroxidase and reductase	Neutralize ROS to protect cells from damage.

3. Role of ROS

Superoxide (O₂⁻): Initial ROS generated.
Hydrogen peroxide (H₂O₂): Further converted to other ROS.
Hypochlorite (HOCl): Highly potent antimicrobial agent produced by myeloperoxidase.

4. Phagolysosome

ROS and lysosomal enzymes are released into the phagolysosome to destroy engulfed pathogens.

Clinical Relevance

1. Chronic Granulomatous Disease (CGD)

Caused by NADPH oxidase deficiency.
Patients rely on H₂O₂ produced by bacteria for ROS generation.
At risk for infections by catalase-positive species (e.g., Staphylococcus aureus, Aspergillus) that degrade H₂O₂, leaving phagocytes ineffective.

2. Catalase-Positive vs. Negative Organisms

Catalase-Positive Organisms	Catalase-Negative Organisms
Neutralize H₂O₂, impairing ROS production.	Do not neutralize H₂O₂, allowing phagocytes to use it.
Examples: S. aureus, Aspergillus	Examples: Streptococcus species

3. Pseudomonas aeruginosa

Produces pyocyanin, a molecule that generates ROS to kill competing pathogens.

4. Lactoferrin

Found in secretory fluids and neutrophils.
Inhibits microbial growth by chelating iron, essential for bacterial survival.

Summary Table: Respiratory Burst Key Players

Component	Role
NADPH oxidase	Generates ROS (superoxide).
Myeloperoxidase (MPO)	Converts H₂O₂ to hypochlorite (HOCl) for microbial killing.
Glutathione system	Protects cells from oxidative damage by neutralizing excess ROS.
Catalase-positive bacteria	Degrade H₂O₂, reducing phagocyte ROS production and increasing infection risk.
Pyocyanin	ROS producer secreted by Pseudomonas aeruginosa to compete with other pathogens.

Points to Remember

Respiratory burst is a key immune mechanism for pathogen destruction via ROS production.
NADPH oxidase deficiency leads to CGD, with susceptibility to catalase-positive organisms.
Myeloperoxidase produces hypochlorite, imparting the characteristic blue-green pigment to sputum.
The HMP shunt is essential for generating NADPH required for oxidative burst.
Iron chelation by lactoferrin adds another layer of microbial growth inhibition.

Bibliography

Abbas, A. K., Lichtman, A. H., & Pillai, S. (2022). Cellular and Molecular Immunology.
Kumar, V., Abbas, A. K., & Aster, J. C. (2021). Robbins and Cotran Pathologic Basis of Disease.

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