Physical Address

304 North Cardinal St.
Dorchester Center, MA 02124

Neonatal Pulmonary Host Defense

Introduction Like the skin and gastrointestinal (GI) tract, the lung is a mucosal organ with a large surface area exposed to the external environment. Unlike the skin and GI tract, the lung is considered to be largely sterile below the glottis, whereas the skin and GI tract are colonized with bacteria termed commensal flora. Despite the lower airway being sterile, the upper airway becomes rapidly colonized…

Immunology of Human Milk

Introduction In 1891, it was discovered in experimental animals that immunity was transmitted through breast-feeding. , In the second decade of the 20th century, the incidence of diarrheal diseases was found to be much lower in breast-fed infants than cow’s milk-fed infants. Those observations were confirmed in developing and industrialized countries. Subsequently it was discovered that breast-feeding protected against many bacterial and viral enteric pathogens. Three…

Cytokines and Inflammatory Response in the Fetus and Neonate

Clinical Relevance of Inflammation in the Fetus and Neonate Thanks to skilled clinicians and cutting-edge technologies, care of the critically ill neonate has advanced significantly since the inception of neonatology. However, interventions presently employed by neonatologists to sustain patients’ lives, including ventilators, antibiotics, and vasoactive medications, to name a few, represent only types of supportive care. Mounting evidence suggests that disturbed homeostasis of the immune system…

The Complement System of the Fetus and Newborn

Introduction The complement system is composed of more than 30 soluble proteins, cell surface regulatory factors, and receptors that work together to accomplish a wide variety of functions. These are important not only in host defense and inflammatory responses but also in normal physiologic homeostasis. By facilitating proper disposal of apoptotic cells and antigens from infectious agents, complement plays an important role in preventing autoimmune and…

Normal and Abnormal Neutrophil Physiology in the Newborn

Introduction The response of the immune-competent host to invasive pathogens includes a variety of local and systemic mechanisms. Among these are humoral elements, such as complement or immunoglobulins (Igs), as well as cellular defenses that involve both innate (nonspecific but immediate) and adaptive (antigen-specific, programmed) immune responses. Neutrophils, or polymorphonuclear cells, comprise a critical arm of the innate immune system (reviewed by Nauseef and colleagues and…

Mononuclear Phagocyte System

Overview of the Mononuclear Phagocyte System The mononuclear phagocyte system (MPS) refers to a network of cells that share the ability to engulf (i.e., internalize) and digest large particles such as whole microbes (e.g., bacteria, fungi, and viruses) or dying cells, but also tumor cells and toxic metabolic products. Mononuclear cells have a single, round nucleus. Neutrophils and other granulocytes also share phagocytic functions, but they…

B-Cell Development

Acknowledgments The authors would like to acknowledge Tucker LeBien for portions of this chapter derived from the previous edition. Introduction Mammalian b-cell development occurs via a series of sequential developmental transitions that culminate in the establishment of a protective antibody repertoire that is essential for the host’s immunity to microbial pathogens. Primary antibody deficiencies can result from mutations in genes that are expressed in B-lineage cells…

T-Cell Development

Acknowledgment The authors wish to thank Marcia McDuffie, MD, Anthony R. Hayward, MD, PhD, and Luigi Notarangelo, MD, PhD, who contributed exceptionally to previous editions of this chapter in the third edition of Fetal and Neonatal Physiology . Introduction Hematopoietic stem cells give rise to committed progenitors of multiple lineages. Whereas maturation along myeloid, erythroid, and megakaryocytic cell lineages occurs within the bone marrow, and differentiation…

Host Defense Mechanisms Against Viruses

Overview of Innate and Adaptive Antiviral Immunity Viral host defense mechanisms of humans depend on a combination of tightly integrated innate and adaptive immune mechanisms. Key innate immune mechanisms include antiviral and proinflammatory cytokines, such as type I interferon (IFN), IFN-γ, and tumor necrosis factor (TNF)-α, which have pleiotropic immunoregulatory effects and multiple potential cellular sources, including mononuclear phagocytes, dendritic cells (DCs), and natural killer (NK)…

Host Defense Mechanisms Against Fungi

Acknowledgments The authors wish to thank Richard B. Johnston, Jr., MD, PhD, who remarkably contributed to this chapter in previous editions of Fetal and Neonatal Physiology . Introduction Fungal infections are commonly classified as either endemic or opportunistic. An endemic fungal infection may occur in any individual living in a geographic area that is the natural habitat of that fungus. Histoplasmosis, coccidioidomycosis, and blastomycosis, which are…

Host Defense Mechanisms Against Bacteria

Introduction Globally, infections cause an estimated 1 million neonatal deaths annually, representing over 40% of all neonatal deaths. , Overwhelming host response to a microbial infection, or neonatal sepsis, is defined as infection in the first 28 days of life; for preterm infants, this period includes up to 4 weeks after the expected due date. This is further subdivided into early-onset neonatal sepsis (EOS), with an…

Platelet–Vessel Wall Interactions

Introduction Platelets are the sentinels of the circulatory system; they recognize and rapidly respond to a disruption in vascular integrity, thereby preventing significant blood loss. This is achieved through the formation of a primary hemostatic plug, which requires platelets to undergo a highly regulated series of events including the adhesion, activation, generation, and release of thrombogenic agents and ultimately aggregation. The importance of these processes is…

Developmental Hemostasis

Introduction The presence of a complex hemostatic system is fundamental to all multicellular organisms with a blood circulatory system. Blood must remain in a fluid form to flow, and for survival, organisms must be able to stop that flow at sites of local injury, through the process of physiologic thrombus formation. However, under certain conditions, thrombus formation can become pathologic. In the mid-1800s Rudolf Virchow described…

Developmental Megakaryopoiesis

Introduction Megakaryocytes (MKs), among the rarest and most unusual hematopoietic cells in the human bone marrow, comprise 0.02% to 0.1% of the total nucleated marrow cells. , Over the past decades, the study of these cells lagged behind that of other hematopoietic lineages, partly because of the rarity and fragility of MKs in the bone marrow, and partly because of the lack of a potent thrombopoietic…

Developmental Erythropoiesis

Acknowledgments Parts of this chapter were adapted from sections of Chapter 134 by authors James A. Stockman III and Pedro A. DeAlarcon in the first edition of this book. We thank Erin Adair for assistance with illustrations. Erythrocyte Kinetics Sites and Stages of Fetal Red Blood Cell Production Extraembryonic Erythropoiesis Extraembryonic erythropoiesis begins in the fetal yolk sac by 14 days’ gestation. Small nests of nucleated…

Neutrophil Granulopoiesis and Homeostasis

Introduction From their initial emergence in the yolk sac at the beginning stages of embryogenesis to their vast proliferation in the bone marrow at the end of term gestation, the differentiation of the pluripotent hematopoietic stem cell into a mature, segmented neutrophil is a tightly controlled process where the transcriptional regulators C/EBP-α and C/EBP-ε have essential roles. Despite their relatively short life span, these intriguing cells…

Developmental Biology of Hematopoietic Stem Cells

Introduction The hematopoietic system is made up of all of the blood cells, including red blood cells, platelets, myeloid cells such as granulocytes, monocyte-macrophages, and dendritic cells (DC), and lymphoid cells such as T, B, and natural killer (NK) cells. Together, these cells function to provide oxygen-carrying capacity, hemostasis, innate and adaptive immune function, and tissue regeneration and repair. Hematopoiesis is the process by which these…

Regulation of Acid-Base Balance in the Fetus and Neonate

Introduction The majority of the existing information on the regulation of acid-base homeostasis in mammals and humans was obtained from studies in adult subjects. Revolution in micromethodology and advances in developmental physiology and molecular biology provided additional insights and improved our understanding of the key mechanisms of fetal and neonatal regulation of acid-base balance. In general, acid-base homeostasis is tightly regulated by extracellular and intracellular buffer…

Fluid Distribution in the Fetusand Neonate

Introduction The human body is composed of fluids and solids (proteins, fat, and minerals). Total body water (TBW) is inversely related to body fat content because fat has very low water content. Body water also contains an array of dissolved substances. Water is the largest single constituent of body composition. TBW is divided into two compartments: intracellular fluid (ICF) and extracellular fluid (ECF). ECF is further…

Response to Nephron Loss in Early Development

Acknowledgments The authors are supported by the following funding: PG: NICHD, Pediatric Scientist Development Program (PSDP) and K12-HD000850. FL: R01DK118140, R01DK107653. JC: R01DK110622, R01DK111861, U34DK117128. Introduction Glomerular endowment is highly variable in humans. Although each kidney contains approximately 1 million nephrons, glomerular number ranges from 210,000 to 2,700,000 per kidney representing a 10-fold difference. , Both environmental and genetic factors influence nephrogenesis, a complex developmental program…