Innate Immunity—Chronic Granulomatous Disease (CGD) CGD results from failure of the phagocyte oxidative burst (NADPH oxidase). Which host defense mechanism is most directly impaired?

Introduction / Context:
Chronic Granulomatous Disease (CGD) is caused by defects in the NADPH oxidase complex that generates reactive oxygen species (ROS) within phagolysosomes. Without an oxidative burst, phagocytes can ingest microbes but have difficulty killing catalase-positive organisms, leading to recurrent infections and granuloma formation. This item targets the specific immune function that fails in CGD.

Given Data / Assumptions:

• NADPH oxidase → superoxide → downstream ROS crucial for microbial killing.
• Phagocytosis is intact; intracellular killing is impaired.
• Greatest susceptibility to catalase-positive pathogens (e.g., Staphylococcus aureus, Serratia marcescens).

Concept / Approach:
Distinguish between uptake (phagocytosis) and killing (oxidative burst). CGD primarily disrupts the killing phase inside neutrophils/macrophages. T-cell cytotoxicity, antigen processing for MHC I, and NK recognition are separate pathways and are not the direct deficit in CGD.

Step-by-Step Solution:

Verification / Alternative check:
DHR (dihydrorhodamine) flow cytometry shows reduced oxidative burst in CGD; nitroblue tetrazolium (NBT) test historically used shows failure to reduce dye.

Why Other Options Are Wrong:

• CTL killing, DC maturation, MHC I processing, NK recognition: not primarily dependent on phagocyte oxidative burst.

Common Pitfalls:
Confusing failure of phagocytosis with failure of killing; overlooking the catalase-positive pathogen pattern.

Final Answer:
Macrophage/neutrophil intracellular killing of bacteria after phagocytosis