Respiratory Burst Introduction to Interferons Clinical Use & Side Effects

Respiratory Burst: Introduction

Also called oxidative burst. Involves the activation of the phagocyte NADPH oxidase complex (e.g., in neutrophils, monocytes), which utilizes O₂ as a substrate. Plays an important role in the immune response, leading to the rapid release of reactive oxygen species (ROS). NADPH plays a role in both the creation and neutralization of ROS. Myeloperoxidase contains a blue-green, heme-containing pigment that gives sputum its color.

Respiratory Burst Pathway

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Key to the Pathway:

• 1. NADPH oxidase: Deficiency leads to chronic granulomatous disease.
• 2. Superoxide dismutase
• 3. Myeloperoxidase
• 4. Catalase/glutathione peroxidase
• 5. Glutathione reductase
• 6. Glucose-6-phosphate dehydrogenase (G6PD)
• GSH/GSSG: Glutathione reduced/oxidized
• HOCl: Hypochlorite bleach
• O₂^–: Superoxide

Clinical Significance of Respiratory Burst

Phagocytes of patients with Chronic Granulomatous Disease (CGD) can utilize H₂O₂ generated by invading organisms and convert it to Reactive Oxygen Species (ROS). However, patients are at increased risk for infection by catalase-positive species (e.g., S. aureus, Aspergillus) capable of neutralizing their own H₂O₂, leaving phagocytes without ROS for fighting infections. Pyocyanin of P. aeruginosa generates ROS to kill competing pathogens. Oxidative burst leads to the release of lysosomal enzymes. Lactoferrin is a protein found in secretory fluids and neutrophils that inhibits microbial growth via iron chelation.

Interferons: Mechanism of Action

Interferons (IFN-α, IFN-β, IFN-γ) are a part of innate host defense. They interfere with both RNA and DNA viruses. Cells infected with a virus synthesize these glycoproteins, which then act on local cells, priming them for viral defense by downregulating protein synthesis to resist potential viral replication and by upregulating MHC expression to facilitate recognition of infected cells. Interferons also play a major role in activating antitumor immunity.

Interferons: Clinical Use and Adverse Effects

Clinical Use:

• Chronic HBV
• Kaposi sarcoma
• Hairy cell leukemia
• Condyloma acuminatum
• Renal cell carcinoma
• Malignant melanoma
• Multiple sclerosis
• Chronic granulomatous disease

Adverse Effects:

• Flulike symptoms
• Depression
• Neutropenia
• Myopathy
• Interferon-induced autoimmunity

Topics Covered:

• Respiratory Burst Introduction
• Respiratory Burst Pathway Diagram
• Respiratory Burst Clinical Aspects
• Interferons Mechanism
• Interferons Clinical Use & Side Effects