Lycke, N., Erlandsson, L., Ekman, L., Schon, K. & Leanderson, T. Lack of J chain inhibits the transport of gut IgA and abrogates the development of intestinal antitoxic protection. J. Immunol. 163 , 913-919

Department of Medical Microbiology and Immunology, University of Göteborg, Sweden.
The Journal of Immunology (Impact Factor: 4.92). 08/1999; 163(2):913-9.
Source: PubMed

ABSTRACT Recent publications have provided confusing information on the importance of the J chain for secretion of dimeric IgA at mucosal surfaces. Using J chain-deficient (J chain-/-) mice, we addressed whether a lack of J chain had any functional consequence for the ability to resist challenge with cholera toxin (CT) in intestinal loops. J chain-/- mice had normal levels of IgA plasma cells in the gut mucosa, and the Peyer's patches exhibited normal IgA B cell differentiation and germinal center reactions. The total IgA levels in gut lavage were reduced by roughly 90% as compared with that in wild-type controls, while concomitantly serum IgA levels were significantly increased. Total serum IgM levels were depressed, whereas IgG concentrations were normal. Following oral immunizations with CT, J chain-/- mice developed 10-fold increased serum antitoxin IgA titers, but gut lavage anti-CT IgA levels were substantially reduced. However, anti-CT IgA spot-forming cell frequencies in the gut lamina propria were normal. Anti-CT IgM concentrations were low in serum and gut lavage, whereas anti-CT IgG titers were unaltered. Challenge of small intestinal ligated loops with CT caused dramatic fluid accumulation in immunized J chain-/- mice, and only 20% protection was detected compared with unimmunized controls. In contrast, wild-type mice demonstrated 80% protection against CT challenge. Mice heterozygous for the J chain deletion exhibited intermediate gut lavage anti-CT IgA and intestinal protection levels, arguing for a J chain gene-dosage effect on the transport of secretory IgA. This study unequivocally demonstrates a direct relationship between mucosal transport of secretory SIgA and intestinal immune protection.

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    • "The production of antigen-specific secretory immunoglobulin A (IgA) dominates the humoral mucosal immune response and provides an important, highaffinity , first line of defence in the intestine by preventing specific pathogens such as Salmonella typhimurium, Shigella flexneri, reovirus and pathogenderived toxins from crossing the intestinal epithelium (Michetti et al. 1992; Lycke et al. 1999; Silvey et al. 2001; Macpherson et al. 2008; Boullier et al. 2009; Mantis et al. 2011). In addition to effects on pathogenic microorganisms, secretory IgA also helps regulate the composition of the commensal gut microbiota (Mantis et al. 2011). "
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    ABSTRACT: Bacterial and viral infections of the gastrointestinal tract are more common in the elderly and represent a major cause of morbidity and mortality. The mucosal immune system provides the first line of defence against pathogens acquired by ingestion and inhalation, but its function is adversely affected in the elderly. This aging-related decline in the immune function is termed immunosenescence and is associated with diminished abilities to generate protective immunity, reduced vaccine efficacy, increased incidence of cancer, inflammation and autoimmunity, and the impaired ability to generate tolerance to harmless antigens. In this review we describe our current understanding of the effects immunosenescence has on the innate and adaptive arms of the mucosal immune system in the intestine. Current estimates suggest that by the year 2050 up to 40 % of the UK population will be over 65 years old, bringing with it important health challenges. A thorough understanding of the mechanisms that contribute to the development of immunosenescence is therefore crucial to help identify novel approaches to improve mucosal immunity in the elderly.
    Biogerontology 04/2014; 16(2). DOI:10.1007/s10522-014-9498-z · 3.29 Impact Factor
    • "Perhaps more informative, therefore , is the J-chain deletion, which abrogates the assembly of polymeric Ig's and thereby prevents the transport and formation of SIgA. Such animals display defective mucosal immunity (Lycke et al., 1999; Schwartz-Cornil et al., 2002). Mice with a deletion in the pIgR gene also lack SIgA (and SIgM) and have impaired epithelial barrier functions (Johansen et al., 1999), which have been shown to result in defects in immune defense (Asahi et al., 2002; Balu et al., 2011; Blutt et al., 2012; Uren et al., 2005) and immune deregulation in allergy (Karlsson et al., 2010). "
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    ABSTRACT: Immunoglobulin A (IgA) is the most heterogeneous of immunoglobulin isotypes, as it occurs in a variety of molecular forms as well as subclasses and allotypes. However, the patterns of heterogeneity vary significantly between different species of mammals and birds. In humans, chimpanzees, gorillas, and gibbons, there are two unique subclasses (IgA1 and IgA2), whereas most other animals that have been investigated have only one, with the remarkable exception of the lagomorphs (rabbits and their allies), which have 13 IgA subclasses. Two, possibly more, allotypes of human IgA2 appear to represent different combinations of constant-region domains of the α-heavy chains. In humans and other primates, the predominant molecular form of circulating (serum) IgA is monomeric, in contrast to the pIgA that is produced in mucosal tissues and transported into the secretions as S-IgA. Further levels of heterogeneity arise from the variable number and composition of the oligosaccharide side-chains present on α-heavy chains. S-IgA antibodies to various viruses can effectively neutralize them. While inhibition of viral binding to cellular receptors is a plausible mechanism in many cases, inhibition of viral replication may occur by other means, depending upon the epitope specificity, isotype, and concentration of antibody as well as the virus and cells involved.
    Mucosal Immunology, 12/2005: pages 267-289; , ISBN: 9780124915435
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    ABSTRACT: Neðst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinn View/Open IgA deficiency is among the most common primary immune deficiency known. Its prevalence, ranging from 1/324-1/1850, depends upon the study group geographic location and its ethnicity. IgA deficiency is commonly associated with other immune defects such as IgG2, and IgG4 deficiency. In addition, ataxia telangiectasia has been associated with IgA deficiency as well. The clinical significans of IgA deficiency is presently unclear. However, increased susceptibility to atopy, autoimmunity, infections and cancer has been reported. Furthermore, majority of these diseases are bound to the mucosal surfaces; the organ where IgA is thought to have its most protective role. Recent studies focusing on the genealogy of primary IgA deficiency have found linkages to chromosome 6, 14, 18 and 22. In addition, a link to certain HLA haplotypes has been reported. Thus, further studies into the immunogenetics of IgA deficiency are needed, particularly focusing upon the question why some individuals with IgA deficiency are prone to diseases whereas others are not. In this article some of these questions are addressed, and the current literature on the topic reviewed. IgA skortur er einn algengasti meðfæddi ónæmisgallinn og ræðst algengi hans meðal annars af kynþætti og þjóðerni. Hjá þjóðum N-Evrópu er algengið á bilinu 1/400-1/700. Einnig er þekkt að aðrir ónæmisgallar eins og IgG2 skortur og Louis-Bar heilkenni (ataxia telangiectasia) finnist hjá einstaklingum með IgA skort. IgA finnst í hvað mestum mæli á yfirborði slímhúðarinnar. Því er athyglivert að IgA skortur eykur líkur einstaklinga á að fá sjúkdóma er herja einna helst á slímhúðina og má þar nefna endurteknar sýkingar, ofnæmi og sjálfsofnæmissjúkdóma. Auk þess virðist þessum einstaklingum hættara við að fá krabbamein. Komið hefur í ljós að í sumum tilvikum hefur IgA skortur legið í ættum. Ættfræðilegar rannsóknir hafa þannig leitt í ljós tengsl við genasvæði á litningum 6, 14, 18 og 22. Auk þess virðast ákveðnar HLA samsætur hafa sterk tengsl við sjúkdóminn. Þrátt fyrir ítarlegar rannsóknir á orsökum og afleiðingum IgA skorts er mörgum lykilspurningum enn ósvarað og þá sérstaklega hvaða aðrir hugsanlegir virkir áhættuþættir leiða til ofangreindra sjúkdóma.
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