China
Africa
Explore chapters and articles related to this topic
Local mucosal allergic disease
Published in Richard F. Lockey, Dennis K. Ledford, Allergens and Allergen Immunotherapy, 2020
Ibon Eguiluz-Gracia, Paloma Campo, Carmen Rondón
The respiratory mucosa harbors a robust population of IgA-producing plasma cells, and IgA is the most abundant immunoglobulin isotype in the airways. A complex of two IgA molecules attached to a J (joining) chain is produced by plasma cells in the lamina propria of the mucosae [15]. This dimeric IgA is taken up by epithelial cells and transported by transcytosis to the luminal surface using the polymeric immunoglobulin receptor (pIgR). A complex formed by parts of pIgR and dimeric IgA, jointly called secretory IgA (SIgA), is cleaved from the membrane of epithelial cells and released into the lumen of the airways. Secretory IgA acts as a neutralizing antibody coating luminal microbes and limiting their contact with stromal and immune cells. IgD is also produced by some plasma cells in the nasal mucosa, and even though the nature of its receptor remains elusive, IgD is able to activate basophils in response to microorganisms commonly found in the nasal cavity [16].
Secretory immunoglobulins and their transport
Published in Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald, Principles of Mucosal Immunology, 2020
Charlotte S. Kaetzel, Jiri Mestecky, Jenny M. Woof
The transport of polymeric immunoglobulins (pIgA and pIgM) across mucosal epithelial cells is mediated by a transmembrane glycoprotein called the polymeric immunoglobulin receptor (pIgR; Figure 11.3). The pIgR binds to the Fc region of polymeric antibodies and can thus be classified as a type of Fc receptor. The single gene encoding pIgR, which is located on chromosome 1 in humans and mice, first emerged in bony fishes and is present in all higher vertebrates. The requirement for pIgR for epithelial transcytosis of SIgA was demonstrated by the finding that pIgR-deficient mice have markedly reduced IgA in external secretions and elevated levels of serum IgA. The magnitude of pIgR-mediated antibody transport is greatest in the gut, resulting in delivery of approximately 3 g per day of SIgA into the intestinal fluids of the average adult. Lesser amounts of SIgM are transported into gut secretions due to the far greater abundance of IgA-producing plasma cells, although SIgM can partially compensate for loss of SIgA in IgA-deficient humans. The pIgR is synthesized as an integral membrane protein in the rough endoplasmic reticulum and is further modified in the Golgi apparatus, including extensive N-linked glycosylation. In the trans-Golgi network, pIgR is sorted into vesicles that deliver it to the basolateral surface of the epithelial cell, where it binds pIgA and pIgM secreted by plasma cells in the lamina propria underlying the epithelium. With or without bound pIg, pIgR is endocytosed and delivered through a series of sorting vesicles to the apical (luminal) membrane of the epithelial cell. During transcytosis, a disulfide bond forms between pIgR and one of the two subunits of dimeric IgA, resulting in a permanent association between the receptor and antibody. Once the pIg–pIgR complex reaches the apical plasma membrane, the extracellular domain of pIgR is proteolytically cleaved to form soluble secretory component. Cleavage of unoccupied pIgR results in release of free secretory component, while cleavage of pIgR bound to pIgA or pIgM results in release of SIgA or SIgM. Many external secretions such as colostrum contain significant amounts of free secretory component, which contributes to mucosal homeostasis by inhibiting the binding of certain microbes and modulating the activity of pro-inflammatory factors. The seven N-glycan chains of human secretory component have a unique structure that is heavily fucosylated and sialylated, similar to those of the antibacterial milk protein lactoferrin. These N-glycans bind a variety of host-, pathogen-, and environment-derived substances with lectin-like activity. Carbohydrate-mediated binding of secretory component to intestinal mucins anchors free secretory component, SIgA, and SIgM to the mucus layer overlying the epithelium, thereby creating an immunologic barrier against infection. Secretory component also stabilizes SIgA by inhibiting the access of microbial proteases to the vulnerable IgA hinge region (see later).
Temporal pathway analysis of cerebrospinal fluid proteome in herpes simplex encephalitis
Published in Infectious Diseases, 2023
Anja Nääs, Peng Li, Clas Ahlm, Elisabeth Aurelius, Josef D. Järhult, Silvia Schliamser, Marie Studahl, Wenzhong Xiao, Jonas Bergquist, Gabriel Westman
After correction for multiplicity, six proteins showed significantly lower levels in the NMDAR seropositive group compared to the seronegative, differing among the three-time points as follows: At T1 – procathepsin H (adj. p-value .021), heparin cofactor 2 (adj. p-value .047), complement factor I (adj. p-value .038), protein AMBP (adj. p-value .021). At T2 – apolipoprotein A1 (adj. p-value .006) (Figure 6). At T3 – polymeric immunoglobulin receptor (adj. p-value .026). No substantial differences in these proteins could be observed in relation to anti-MNDAR IgG titres among the seropositive patients. No significant differences in individual proteins were found in relation to corticosteroid treatment, size of brain MRI lesion or neurocognitive performance.
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
As discussed, the inhibitory effect of IgA on B cell activation observed in our experiments might be mediated through a unique mechanism that differs from those reported previously. The effects of other well-known IgA receptors, the asialoglycoprotein receptor and the polymeric immunoglobulin receptor, are not consistent with the functions revealed here [22,35]. Although we did not identify the direct target of OA-4 that suppresses splenic B cell activation, our findings suggest the possible existence of a novel IgA receptor that suppresses CD22 phosphorylation and its signaling pathways, such as ERK. The target molecule might be expressed on splenic B cells but not A20 B lymphomas, because anti-BCR antibody-induced ERK phosphorylation in A20 B lymphomas was not attenuated by OA-4 (Figure 5(A)) despite its inhibition in splenic B cells (Figure 3(A)). IgA and IgM receptors, Fcα/µR (CD351) are conserved among humans and mice and might be the potential targets of mouse dimeric IgA OA-4, which exerts inhibitory effects on mouse B cells, although the functions of the receptor after stimulation with IgA have not been elucidated. Further experiments to identify the direct target molecule of IgA are required.
Gut microbiota derived metabolites contribute to intestinal barrier maturation at the suckling-to-weaning transition
Published in Gut Microbes, 2020
Martin Beaumont, Charlotte Paës, Eloïse Mussard, Christelle Knudsen, Laurent Cauquil, Patrick Aymard, Céline Barilly, Béatrice Gabinaud, Olivier Zemb, Sandra Fourre, Roselyne Gautier, Corinne Lencina, Hélène Eutamène, Vassilia Theodorou, Cécile Canlet, Sylvie Combes
Regarding the epithelial transcytosis of immunoglobulin A (IgA), the gene expression of the “polymeric immunoglobulin receptor” (PIGR) was more than 10-fold up-regulated after PND25 (Figure 4(a)). This was associated with an up-regulation of the survival signal for IgA-secreting plasmocyte “B cell activation factor” (TNFSF13Bcoding for the protein BAFF) while the expression of “proliferation-inducing ligand” (TNFSF13 coding for the protein APRIL) was not changed (Figure 4(a)). Interestingly, the concentration of IgA in the cecum (both from maternal milk and endogenous origin) decreased from PND25 (Figure 4(b)). Among the cytokines tested, the gene expression of “interleukin-4” (IL4), “tumor necrosis factor” (TNF) and “transforming growth factor β1” (TGFB1) were down-regulated at PND25 compared to PND18 (Figure 4(c)). In contrast, the gene expression of “C-C motif chemokine ligand 20” (CCL20) was strongly up-regulated after the onset of solid food ingestion (Figure 4(c)). Finally, among a panel of genes involved in redox signaling, “glutathione peroxidase 2” (GPX2) and “nitric oxide synthase 2” (NOS2) were up-regulated from PND25 (Figure 4(d)). In summary, the expression of genes involved in the gut barrier function were highly regulated during the transition from maternal milk to solid food.