Neonatal Gastrointestinal Innate Immunity

Objectives

After completing this article, readers should be able to:

1. Describe the largest surface area of the body that separates the external from the internal environment and the first line of defense that prevents breakdown of this barrier.

2. Delineate the components of the innate immune system.

3. Characterize some of the agents that mediate interplay between the innate and adaptive immune systems.

4. Describe how the integrity of the gastrointestinal innate immune system may relate to specific autoimmune diseases.

Introduction

Evidence is accumulating that the defense mechanisms in the newborn that normally maintain a healthy balance in the intestine (both immune and nonimmune) may be inadequate or at least not functioning at levels observed in adults. Infants, particularly undernourished infants, may be at an increased risk for luminal proliferation of and mucosal invasion by microbial pathogens and intact dietary antigens.

The gastrointestinal (GI) tract presents the largest surface area of the body to which antigens and microbes are exposed. The intestine, therefore, must have intricate mechanisms to allow entry of nutrients and other beneficial molecules while preventing potentially harmful microbes and other agents from gaining entry into the inner milieu. Several factors lead to a hostile GI environment that predisposes the preterm infant to disease. These include the introduction of feeding tubes into the stomach or more distal intestine, the routine use of broad-spectrum antibiotics that select for resistant pathogens that thrive in the unusual microbial environment of the neonatal intensive care unit, intrinsic immaturities of the infant GI tract, and the lack of adequate nutrition.

Intestinal defenses may be broadly divided into immune and nonimmune categories. The nonimmune system sometimes also is referred to as the innate immune system (Fig. 1). Although there is considerable overlap between the immune and nonimmune systems, this review focuses primarily on the innate arm of the intestinal …