DEVELOPMENT OF IMMUNE FUNCTION IN THE INTESTINE AND ITS ROLE IN NEONATAL DISEASES
Section snippets
ONTOGENY OF MUCOSAL IMMUNITY
In addition to the passive immune protection acquired from the mother, neonates require their own immune system to respond appropriately to foreign antigens. Gut-associated immunity develops in parallel with the other central lymphoid organs, such as the thymus. In particular, the presence of Peyer's patches parallels the development of the spleen and peripheral lymph nodes.
T lymphocytes do not populate the intestine until the thymus is mature. T-cell precursors are derived from hematopoietic
THE MUCOSAL DEFENSE BARRIER
For the intestine to mount a proper immune response against potentially harmful antigens and microorganisms, a significant degree of luminal surveillance must occur, which is the capacity of the gut epithelia to modulate antigen transport to induce beneficial mucosal immune responses rather than adverse reactions. For efficient surveillance, antigens must be presented and transported across the gut in a balanced manner to prevent deleterious immune responses. Excess or inappropriate antigen
CYTOKINES AND GROWTH FACTORS IN THE MUCOSAL IMMUNE SYSTEM
The term cytokine refers to proteins secreted by cells in response to a variety of inducing stimuli. These molecules, in turn, influence the behavior of target cells via a surface receptor. Three types of cytokinecell interactions exist, with a response coming only from cells expressing suitable receptors. Autocrine stimulation occurs when the secreting cell possesses receptors to its own cytokines. Localized paracrine stimulation occurs if a secretory cell influences adjacent cells toward
BACTERIAL ADHERENCE AND MUCOSAL IMMUNITY
The first step in gaining access to the human host for bacteria and other pathologic microorganisms includes successful adhesion to the intestinal surface. The tendency for bacteria to grow attached to surfaces has long been recognized.70 Moreover, the crucial role of adherence in intestinal virulence was demonstrated initially in piglet diarrheal studies caused by Escherichia coli. The virulence was associated with a DNA plasmid encoding the K88 fimbrial adhesin (adherence molecule) and
NEONATAL DISEASE AND GUT-ASSOCIATED IMMUNE FUNCTION
In this section, three common and sometimes life-threatening conditions that afflict premature and term neonates are discussed. Emphasis is placed on the immunologic basis for the pathophysiology of these disease states.
SUMMARY
This review has traced the ontogeny of the human mucosal immune system, speculating that appropriate gut immune responses are essential in preventing many significant neonatal enteric diseases. Because the gastrointestinal tract serves as the portal of entry for many potential antigens, its mucosal immune function is essential in controlling antigenic responses and ensuring systemic tolerance. A thorough understanding of the development of the entire immune system is essential in defining
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Address reprint requests to Robert M. Insoft, MD, Division of Neonatology, Massachusetts General Hospital, Founders House 442, Fruit Street, Boston, MA 02114
This work was supported by grants HD-12437, HD-31812, P01-DK-33506, and P-30-DK40561 from the National Institutes of Health and a grant from the Crohn's and Colitis Foundation of America.
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From the Department of Pediatrics (RMI), and the Developmental Gastroenterology Laboratory, Combined Program in Pediatric Gastroenterology and Nutrition, Massachusetts General Hospital (IRS, WAW), Harvard Medical School (RMI, IRS, WAW), and Children's Hospital (WAW), Boston, Massachusetts