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The Inducible Defense System: Antibody Molecules and Antigen-Antibody Reactions
Published in Julius P. Kreier, Infection, Resistance, and Immunity, 2022
IgA may occur as a monomer or as a polymer of two to five subunits. In serum, IgA exists primarily as a monomer (90 percent) with some polymeric forms, mostly dimers and trimers. Like IgM, the J (joining) chain helps bind the IgA subunits together. IgA present in extracellular secretions is referred to as secretory IgA. Secretory IgA is a dimer, consisting of two monomeric IgAs, a J chain and a nonimmuno-globulin glycoprotein called the secretory component (M.W. 85,000 dal tons). After release from the plasma cell, IgA may bind to a poly-lg receptor on epithelial cells. This binding process induces the transport of the IgA molecule through the endothelial cell by transcytosis. During the transport process, the poly-lg receptor is cleaved and a portion of it, called the secretory component (SC), becomes bound to dimeric IgA (Figure 7.11). The SC is thought to make the IgA molecule resistant to attack by proteolytic enzymes.
Diarrhea and Malnutrition
Published in Fima Lifshitz, Childhood Nutrition, 2020
Andrea Maggioni, Fima Lifshitz
The number of B cells are normal or elevated,61 accounting in part for the normal or elevated immunoglobulin titers. Many authors have speculated that the elevated immunoglobulin levels may be secondary to an increased exposure to various infectious agents to which the malnourished child may not be able to respond. This may not mean that the humoral system is intact; what may be decreased is the antibody affinity,62 thus accounting for a higher frequency of antigen antibody complexes found in such patients.63 A significant decrease in secretory IgA and secretory component levels associated with malnutrition has also been reported.64
Candidiasis
Published in Rebecca A. Cox, Immunology of the Fungal Diseases, 2020
Judith E. Domer, Emily W. Carrow
Since C. albicans regularly colonizes mucocutaneous tissues and can initiate disease at the same sites, a number of studies have been conducted in which IgA has been the principal immunoglobulin under study. Most of these studies have involved attempts to correlate IgA levels, either in serum or cervicovaginal secretions, with vaginitis caused by Candida. Mathur et al. ,152 for example, examined the sera of three patients with vaginal candidiasis and found that the anti-Candida antibody in those sera was in the IgA fraction. Using unfractionated sera in a hemagglutination assay, they also noted that normal subjects had anti-Candida titers ranging from 0 to 1:16, whereas patients with candidal vaginitis had titers ranging from 1:4 to 1:256. Five of the ten patients examined had titers ≥1:75. Interestingly, the IgA detected in serum appeared to contain secretory component, suggesting that it had been produced at mucocutaneous surfaces and from there made its way into the circulation. Others153 have found the predominant anti-Candida immunoglobulin class in serum in patients with vaginal candidiasis to be IgG.
Engineering a pure and stable heterodimeric IgA for the development of multispecific therapeutics
Published in mAbs, 2022
Florian Heinkel, Meghan M. Verstraete, Siran Cao, Janessa Li, Patrick Farber, Elizabeth Stangle, Begonia Silva-Moreno, Fangni Peng, Surjit Dixit, Martin J. Boulanger, Thomas Spreter Von Kreudenstein, Eric Escobar-Cabrera
Beyond greatly expanding the accessible formats and geometries of a monomeric antibody as has been seen for IgG,40 a heterodimeric IgA Fc also enables a new category of multispecific, multimeric monoclonal antibodies. One feature of IgA is that a higher valency is naturally accessible via J-chain-based multimers.17,32 These multivalent formats can provide avidity effects that increase apparent affinity of low-affinity paratopes and increase clustering and specificity for target cells with high receptor density.17,41 Furthermore, the presence of the J-chain enables covalent interaction of dimeric IgA with pIgR for transcytosis of the mucosa, leaving multimeric IgA bound to the secretory component.42 This feature of IgA could be used to direct a multispecific, multimeric antibody to mucosal environments following intravenous administration.43 Combining this higher valency with a heterodimeric IgA Fc gives rise to geometries and valencies of formats that were previously inaccessible and an opportunity to deliver multispecific IgA to mucosal environments (Figure 5).
Kidney microbiota dysbiosis contributes to the development of hypertension
Published in Gut Microbes, 2022
Xin-Yu Liu, Jing Li, Yamei Zhang, Luyun Fan, Yanli Xia, Yongyang Wu, Junru Chen, Xinyu Zhao, Qiannan Gao, Bing Xu, Chunlai Nie, Zhengyu Li, Aiping Tong, Wenjie Wang, Jun Cai
The tissues were fixed in 4% paraformaldehyde (PFA) overnight at 4°C and washed thrice with PBS before storing in 70% ethanol. Tissues were routinely processed, paraffin-embedded, sectioned, and stained using Molecular Pathology Core at Sichuan University. Tissues were immune-stained using paraffin-embedded slides that were de-paraffinized, and antigen retrieval was performed by incubating the samples in citrate buffer (Sigma-Aldrich, St. Louis, MO, USA) heated in a microwave oven. The samples were subsequently incubated in blocking buffer (5% normal goat or mouse serum in PBS, depending on the species of primary antibody) for 30 min at room temperature and then incubated with one of the following primary antibodies: anti-IgA secretory component antibody (Abcam, ab212330); anti-Staphylococcus aureus (Abcam, ab20920). After washing thrice with PBS, the tissue samples were incubated with fluorescent-conjugated secondary antibody, followed by DAPI nuclear staining. Biotinylated secondary antibody was added, followed by staining with an avidin-biotin complex and counterstaining with hematoxylin.
Immunoglobulin a suppresses B cell receptor-mediated activation of mouse B cells with differential inhibition of signaling molecules
Published in Immunopharmacology and Immunotoxicology, 2022
Kouya Yamaki, Masato Terashi, Saori Yamamoto, Rei Fujiwara, Jun-ichi Inoue, Kishi Shimizu, Sakura Yanagita, Yuma Doi, Kei-ichiro Kimura, Kayo Kotani, Mai Sugihara, Yutaka Koyama
IgA is the second most common Ig isotype after IgG, accounting for 15% of blood immunoglobulins, and it exists in monomeric and dimeric forms in the serum. In mucus, tears, and saliva, the major Ig form is secretory IgA consisting of a J chain and a secretory component bound to a dimer IgA, which protects against bacterial infection [16,17]. However, the role of IgA is poorly understood. Considering the variety of homeostasis regulating pathways in animals, we hypothesized that IgA is an immunosuppressive counterpart of immunoactivating isotypes, including IgG, IgE, and IgM, which increase antibody production as reported by Professor Heyman [18]. To this end, we have investigated the immunosuppressive roles of IgA with respect to mouse B cell activity in vivo for several years. As a result, we established mouse monoclonal IgA-producing hybridomas and demonstrated that unlike other isotypes, IgA suppresses de novo antibody production by inhibiting B cell activation in vivo [19]. Diana et al. [20] reported that dendritic cell-specific ICAM-3 grabbing nonintegrin receptor 1 (SIGN-R1), denoted as C-type lectin mediates the anti-inflammatory effect of secretory IgA, whereas dimeric IgA does not exhibit an inhibitory effect in mice. Thus, the inhibitory effects of dimeric IgA on mouse B cells observed in our previous studies were not mediated through SIGN-R1.