The ontogeny of serum IgA in the newborn

Weaver, Lawrence T.; Wadd, N.; Taylor, Claire; Greenwell, J. Richard; Toms, G. L.

doi:10.1111/j.1399-3038.1991.tb00185.x

Cited by 26 publications

(8 citation statements)

References 20 publications

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“…This can add to the cytokine-stimulated enhancement of pIgR ⁄ SC expression [21,26]. Uptake of SIgA antibodies from breast milk via the human neonatal gut mucosa is negligible, however, and probably of no immunological importance except perhaps in preterm infants [75]. So-called gut closure normally occurs mainly before birth, but the mucosal barrier may be inadequate up to 2 years of age.…”

Section: Development Of Secretory Immunitymentioning

confidence: 99%

Mucosal Immunity: Induction, Dissemination, and Effector Functions

2009

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Prevention of infections by vaccination remains a compelling goal to improve public health. Most infections involve the mucosae, but the development of vaccines against many of these pathogens has yet to be successful. Mucosal vaccines would make immunization procedures easier, be better suited for mass administration, and most efficiently induce immune exclusion – a term coined for non‐inflammatory antibody shielding of internal body surfaces – mediated principally by secretory immunoglobulin A (SIgA). The exported antibodies are polymeric, mainly IgA dimers (pIgA) – produced by local plasma cells stimulated by antigens that target the mucosae. SIgA was early shown to be complexed with an epithelial glycoprotein – the secretory component (SC). In 1974, a common SC‐dependent transport of pIgA and pentameric IgM was proposed. From the basolateral surface, pIg‐SC complexes are taken up by endocytosis and finally extruded into the lumen. Membrane SC is now referred to as polymeric Ig receptor (pIgR). In 1980, it was shown to be synthesized as a larger transmembrane protein – first cloned from rabbit and then from human. Mice deficient for pIgR showed that this is the only receptor responsible for epithelial transport of IgA and IgM. In the gut, induction of B cells occurs in gut‐associated lymphoid tissue, particularly the Peyer’s patches, but also in mesenteric lymph nodes. Plasma cell differentiation is accomplished in the lamina propria to which the memory/effector cells home. The airways also receive such cells from nasopharynx‐associated lymphoid tissue – but by different homing receptors. Such compartmentalization is a challenge for development of mucosal vaccines.

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Section: Development Of Secretory Immunitymentioning

confidence: 99%

Mucosal Immunity: Induction, Dissemination, and Effector Functions

2009

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“…Sequencing of free SC isolated from human colostrum (46) and cloning of rabbit transmembrane SC cDNA (79) revealed five extracellular domains with considerable Ig homology, especially to the Ig V, and Ig VH domains. Each SC domain was found to consist of [100][101][102][103][104][105][106][107][108][109][110][111][112][113][114][115] residues and to be stabilized by disulphide bridges between paired cysteines. Subsequent cloning of human SC cDNA made it possible to deduce the complete amino-acid sequence of this pIg receptor, including the signal peptide (I8 residues) and 746 amino acids (the mature transmembrane SC) extending 187 residues more at the C terminus than does free SC (63,64).…”

Section: P K Sc Homology Among Various Speciesmentioning

confidence: 99%

“…In addition, satisfactory internal antibody protection of their mucosae is usually provided by circulating maternal IgG, which is distributed extravascularly at a ratio of 50%60% (102). Selective placental transfer of IgG in the foetus is unique for primates (72), and postnatal uptake of breast milk-derived macromolecules seems to be of minor importance in supporting specific systemic immunity in humans (87), except perhaps in the preterm infant (103).…”

Section: Introductionmentioning

confidence: 99%

Molecular and cellular aspects of the secretory immunoglobulin system*

Brandtzæg

1995

APMIS

209

136

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Molecular and cellular aspects of the secretory immunoglobulin system. APMIS 103:Adaptive immunological protection of mucous membranes is provided mainly by secretory IgA antibodies. Such "first line" defence is accomplished through a unique cooperation between the mucosal B-cell system and the secretory component (SC) expressed basolaterally on glandular epithelial cells. This transmembrane glycoprotein is quantitatively the most important receptor of the immune system because it is responsible for external transport of locally produced polymeric IgA (pIgA), which is the major product of humoral immunity. Transmembrane SC belongs to the Ig supergene family and functions as a general pIg receptor, also mediating the external translocation of pentameric IgM to form secretory IgM. The B cells responsible for local pIg production are intitally stimulated in lymphoepithelial structures, particularly the Peyer's patches in the distal small intestine, from which they migrate as memory cells to exocrine tissues all over the body. Mucous membranes are thus furnished with secretory antibodies in an integrated way, ensuring a variety of specificities at every secretory site. There is currently great interest in exploiting this integrated or "common" mucosal immune system for oral vaccination against pathogenic infectious agents. However, much remains to be learned about mechanisms for antigen uptake and processing necessary to elicit mucosal immunity as well as the molecular biology and cytokine regulation of SC-dependent pIg transport. Moreover, evidence is emerging for the existence of subcompartmentalization in the mucosal immune system, particularly a dichotomy in cellular migration between the gut and the upper airway, which may complicate the design of efficient local vaccines.

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“…Indeed, a bi-directional transport mechanism for IgG was recently demonstrated in a human intestinal epithelial cell line [4], but the biological significance of this putative function in the newborn remains unknown. Intestinal uptake of secretory IgA (SIgA) antibodies after breast-feeding appears to be of little or no importance in the support of systemic immunity in the neonatal period [5], except perhaps in the preterm infant [6]. Gut closure in humans normally seems to occur mainly before birth, but the different variables involved in this process are poorly defined.…”

Section: Antibody-mediated Defence In the Human Neonatementioning

confidence: 99%

Ontogeny of the intestinal immune system in the premature infant

Brandtzæg

2001

Monatsschrift Kinderheilkunde

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A variety of variables influence the development of secretory immunity and oral tolerance, two immune mechanisms that are of paramount importance for the mucosal barrier function.Epithelial permeability is likely a significant primary or secondary event in the pathogenesis of several intestinal diseases, including adverse immune reactions to foods.This variable is determined by the individual's age (e.g., preterm versus term infant), concurrent infections, and the shielding effect of secretory IgA (SIgA) antibodies provided by breast milk.The clinical consequences will depend on how fast "closure"of the epithelial barrier can be attained or reestablished, which is influenced both by the age of the infant and by its successful mounting of adaptive intestinal SIgA responses as well as generation of oral tolerance towards innocuous antigens from the diet and from the normal indigenous microbiota.SIgA is the best defined effector component of the mucosal immune system; its enhancement, and the homeostatic mucosal immune regulation in general, induced by probiotic commensal bacteria is of considerable clinical interest.Importantly, the feeding and treatment regimen (e.g., antibiotics) to which the newborn is subjected, may disturb the balance of the developing mucosal immune system.

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The ontogeny of serum IgA in the newborn

Cited by 26 publications

References 20 publications

Mucosal Immunity: Induction, Dissemination, and Effector Functions

Mucosal Immunity: Induction, Dissemination, and Effector Functions

Molecular and cellular aspects of the secretory immunoglobulin system*

Ontogeny of the intestinal immune system in the premature infant

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