Chronic Granulomatous disease is a:
|A||B Cell Defect|
|B||T Cell defect|
|D||Disorder of Phagocytosis|
a. Chronic granulomatous disease (CGD) is the most common of the inherited disorders of phagocyte function.
b. The pivotal role of the respiratory burst (which follows within seconds after phagocytes are activated) in the subsequent effective killing of catalase-positive microbes became evident from studies of patients with CGD.
c. The NADPH oxidase that catalyzes the respiratory burst is found exclusively in phagocytes and remains dormant unless activated by a variety of particulate and soluble stimuli, such as opsonized microbes and chemotactic peptides.
d. These stimuli excite a transmembrane electron transport system in which NADPH on the cytoplasmic side of the membrane reduces oxygen through a series of reactions involving flavin adenine dinucleotide (FAD), several soluble cofactors, and membrane-associated cytochrome b. Oxygen is reduced through a univalent reduction to superoxide anion and is rapidly mutated to hydrogen peroxide and hydroxyl radicals.
e. The latter two products are thought to be the principal means by which microbial killing or tissue damage takes place. Of the components of the phagocyte NADPH oxidase complex, the membrane components, a hemoprotein heterodimer with subunits of 91 kD and 22 kD, require at least two cytosolic protein components of 47 kD and 67 kD to achieve maximal oxidase activity.
f. The X-linked and autosomally inherited forms of the disease are associated with missing components or subunits.
g. The CGD gene is located on the X chromosome proximal to the muscular dystrophy gene and distal to the ornithine transcarbamylase gene on the Xp21 band. The protein encoded by the X-CGD gene is synonymous with the 91-kD subunit of the cytochrome b complex. A reservoir of cytochrome b (~80-90%) is found in neutrophil-specific granules and is translocated to the membrane on activation of the cell.