Chapter 51: Phagocytic Disorder

INTRODUCTION

Phagocytosis is the process by which leukocytes internalize particles larger than 1 μm, such as microbes, apoptotic cells, and chemical substances.¹ It is an essential component of the innate and adaptive immune response, as well as tissue remodeling and repair.² Neutrophils, macrophages, and dendritic cells are professional phagocytes that are derived from the common myeloid progenitor.³ As the invading microbes cross the skin and mucosal barrier and enter the tissue, they are recognized by resident macrophages and dendritic cells through germline-encoded pattern recognition receptors. The release of proinflammatory cytokines activates local endothelial and epithelial cells, which express chemoattractants and adhesion molecules. Circulating neutrophils adhere to the endothelium and migrate through the endothelial lining into the tissues.^{4, 5}

Phagocytosis is a receptor-mediated process. Apart from pattern recognition receptors, foreign particles bound by complements and immunoglobulins in the circulation and interstitial fluid are recognized by phagocytes through the opsonic receptors.^{6, 7} The ingested microorganism is degraded in the phagolysosome, and the presentation of antigenic peptide on the surface of the phagocytes leads to lymphocyte activation. The mechanism of killing is accomplished by de novo synthesis of reactive oxygen species and release of proteases stored in lysosomal granules into the phagolysosome.

Phagocytosis is the first line of defense against infection and forms the link between innate and adaptive immunity.⁸ Phagocytic defects commonly present in the neonatal period and early infancy. The spectrum of disorders includes numerical deficiency and functional defects such as impaired adhesion, chemotaxis, ingestion, degranulation, and intracellular killing.

PATHOPHYSIOLOGY

Neutrophil Count in the Neonates

The absolute neutrophil count (ANC) is calculated by multiplying the total white blood cell count (WCC) by the percentage of bands and mature neutrophils. The ANC of the newborn varies with gestational age, postnatal age, birth weight, geographical factors such as altitude, and clinical factors, including intrapartum oxytocin administration and maternal hypertension.^{9, 10, and 11} The commonly used ANC reference range in term and near-term neonates was established in 1979 by Manroe et al.¹² At birth, the ANC ranges from 1800 to 5500/mm³, which subsequently increases 3- to 5-fold and peaks at 12–18 hours of life. Gradual fall in ANC occurs by 24 hours, ranging from 1800 to 7200/mm³ at 60 hours and remaining at 1800 to 5400/mm³ within the first 28 days. The ANC reference range in very low birth weight (VLBW) neonates was published in 1994 by Mouzinho et al.¹³ In their study of 193 premature infants born at mean gestational age of 29.5 weeks with mean birth weight of 1157 g, the lower boundary of ANC was found to be 500/mm³ at birth, rose less steeply to 2200/mm³ at 18–20 hours, then decreased to 1100/mm³ at 60 hours. From 60 hours to 28 days of life, ...