PG Quie

Abstract

Patients with congenital disorders of the phagocytic system have served as "nature's own experiments" demonstrating the importance of specific functions of phagocytic cells for host defense against bacterial and fungal infections. Patients with Leukocyte Adherence Deficiency (LAD) stimulated research on surface receptors involved in margination and diapedesis of leukocytes from the circulation into tissues. Patients with Chronic Granulomatous Disease (CGD), who are unusually susceptible to serious infections from catalase positive bacteria and fungi, revealed the importance of a respiratory oxidative response of phagocytes. We have learned that products of oxidative metabolism are essential for efficient intracellular killing of microbes by neutrophils and macrophages. Patients with Job's Syndrome suffer recurrent infections related to dysfunction of neutrophils which may be secondary to cytokine dysregulation. These patients have taught us the importance of immunologic "discipline" for normal function. Patients described in this review with congenital disorders of the phagocytic system may be rare, but the lessons they provide are applicable to many more patients with acquired or transitory disorders of phagocytes. We continue to be amazed by this remarkably complex and essential host-defense system.