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Interestingly, we detected significantly elevated IgG2 levels in the combined bronchial asthma group, which was attributable to an IgG2 increase in exogenous and endogenous bronchial asthma but not the mixed-type bronchial asthma group (Figure 1F). A total of 112 male and female subjects (controls I n i = 30, exogenous bronchial asthma I n i = 33, endogenous bronchial asthma I n i = 24, mixed-type bronchial asthma I n i = 25) between the age of 18-82 years were included in this cross-sectional study (Table 1). Keywords: bronchial asthma; microbiome; polymeric immunoglobulin receptor; secretory immunity; upper respiratory tract EN bronchial asthma microbiome polymeric immunoglobulin receptor secretory immunity upper respiratory tract 1213 1218 6 10/13/22 20221001 NES 221001 Key messages pIgR-mediated secretory immunity in the nasopharynx is not altered in mild bronchial asthma. Importantly, as the role of allergy (i.e. reactivity to aeroallergens) for bronchial asthma-related changes in the nasal microenvironment had so far not been addressed, we comparatively assessed mucosal Ig responses and the composition of the microbiota in 3 asthmatic patient cohorts (exogenous, endogenous and mixed-type bronchial asthma). [Extracted from the article]

Age-related changes in the oral mucosa immunity, including decreased contents of secretory immunoglobulins and antimicrobial peptides in saliva, along with changed balance of pro- and antiinflammatory cytokines, care risks for development of purulent-inflammatory or allergic diseases of the oral cavity. For example, denture stomatitis (DS) caused by Candida albicans occurs in about 30—70% of denture users. The purpose of this study was to assess the secretory immune state of oral mucous membranes in the patients with Candida-associated denture stomatitis. We examined 42 elderly patients (61-72 years old) with one-piece acrylic dentures for at least, 6 months (15 men and 27 women). Based on clinical and microbiological studies, the patients were divided into a group with DS (n = 24) and a group without DS (n = 18). The contents of secretory immunoglobulin A (sIgA) and proinflammatory cytokines was determined, i.e., interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNFα), and anti-inflammatory cytokines, e.g., receptor antagonist of interleukin-1 (RAIL), interleukin-4 (IL-4), interleukin-10 (IL-10), as well as antimicrobial peptides (cathelicidin LL-37, lactoferrin and alphadefensins 1-3 (HNP1-3). The sIgA levels in the salivary fluid of patients with DS (0.92 (0.80-1.26) g/l) were significantly lower (p < 0.05) than in patients without stomatitis (1.71 (1.23-2,13) g/l). In the group with advanced DS, a significant increase of IL-1β levels in saliva was observed, along with simultaneous decrease of IL-8 concentrations, compared to the other group, without differences in TNFα and IL-6 concentrations. Increased contents of IL-10 in saliva was also noted. It was shown that the concentrations of cathelicidin LL-37 in saliva of the DS patients was increased two-fold, whereas the contents of neutrophil-derived alpha-defensins (HNP 1-3) was decreased. Conclusions: The development of inflammation in denture stomatitis caused by usage of removable acrylic dentures associated with Candida albicans infection is characterized by functional insufficiency of the secretory immunity of the oral mucosa associated with decreased amounts of secretory immunoglobulin A and antimicrobial peptides of neutrophilic origin. Low levels of alpha-defensins may suggest a decrease in the functional activity of neutrophils in the elderly, thus leading to higher susceptibility to fungal infection of oral cavity.

Purpose: Transport of secretory immunoglobulin A (SIgA) through the airway epithelial cell barrier into the mucosal lumen by the polymeric immunoglobulin receptor (pIgR) is an important mechanism of respiratory mucosal host defense. Identification of immunomodulating substances that regulate secretory immunity might have therapeutic implications with regard to an improved immune exclusion. Thus, we sought to analyze secretory immunity under homeostatic and immunomodulating conditions in different compartments of the murine upper and lower respiratory tract (URT&LRT). Methods: Pigr gene expression in lung, trachea, and nasal-associated lymphoid tissue (NALT) of germ-free mice, specific pathogen-free mice, mice with an undefined microbiome, as well as LPS- and IFN-γ-treated mice was determined by quantitative real-time PCR. IgA levels in bronchoalveolar lavage (BAL), nasal lavage (NAL), and serum were determined by ELISA. LPS- and IFN-γ-treated mice were colonized with Streptococcus pneumoniae and bacterial CFUs were determined in URT and LRT. Results: Respiratory Pigr expression and IgA levels were dependent on the degree of exposure to environmental microbial stimuli. While immunostimulation with LPS and IFN-γ differentially impacts respiratory Pigr expression and IgA in URT vs. LRT, only prophylactic IFN-γ treatment reduces nasal colonization with S. pneumoniae. Conclusion: Airway-associated secretory immunity can be partly modulated by exposure to microbial ligands and proinflammatory stimuli. Prophylactic IFN-γ-treatment modestly improves antibacterial immunity in the URT, but this does not appear to be mediated by SIgA or pIgR. [ABSTRACT FROM AUTHOR]

Abstract—The goal of the work was to study the effect of peptide bioregulation on the mucosal immunity state of elderly patients during the complex treatment of chronic generalized periodontitis. The results were evaluated based on the saliva immunological parameters of 46 patients aged 61–69 years suffering from chronic generalized periodontitis of moderate severity before treatment and 2 months after the completion of treatment with the Vizulingval peptide complex as a peptide bioregulator. The index of oral hygiene and the intensity of gingival inflammation were studied during clinical patient examinations. A decrease in the concentration of proinflammatory cytokines IL-1β, TNF-α, and IL-8 with a simultaneous increase in the IL-10 anti-inflammatory cytokine was noted in the salivary fluid of patients subjected to bioregulatory therapy. The therapy also led to an enhancement of the local immunity of the oral mucosa, which was manifested by an increased synthesis of the secretory immunoglobulin A. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine if intense training coupled with dehydration methods implemented to lose weight had an effect on the variability of stress hormones resulting in suppression of resting salivary concentrations of secretory Immunoglobulins (slg) in wrestlers. Eleven wrestlers (21.3 ± 1.7 years of age) were placed in either the experimental or control group based on whether they were subjected to water cuffing (treatment) in preparation for competition. Saliva samples were obtained at rest and post-training over a two-week preparation period, and one day following competition. Saliva samples were assayed for testosterone, cortisol, slgA and slgG. The experimental group significantly decreased weight over the course of the study while the controls maintained a steady weight. Significant acute post-training increases were found in slgA, slgG, testosterone and cortisol within each group. Although there was no significant treatment X time interaction, the percent hormonal increases were higher in the experimental group (16 and 22% for testosterone and cortisol, respectively) than the controls (6 and 12% for testosterone and cortisol, respectively). There was no effect of training and treatment on T:C ratio, reflecting a balance in the anabolic-catabolic state of the wrestlers. The percent coefficient of variation of post-training T:C was negatively related to resting levels of slgG, indicating that higher the variability of the T:C response, the lower the slgG. This correlation, however, was not significant for slgA. In conclusion, water cuffing did not have an effect on slgG, slgA, cortisol, and testosterone levels. These parameters seem to depend more on training instead of water cuffing in wrestlers. [ABSTRACT FROM AUTHOR]

Abstract: Mucosal epithelia comprise an extensive vulnerable barrier which is reinforced by numerous innate defence mechanisms cooperating intimately with adaptive immunity. Local generation of secretory IgA (SIgA) constitutes the largest humoral immune system of the body. Secretory antibodies function both by performing antigen exclusion at mucosal surfaces and by virus and endotoxin neutralization within epithelial cells without causing tissue damage. SIgA is thus persistently containing commensal bacteria outside the epithelial barrier but can also target invasion of pathogens and penetration of harmful antigens. Resistance to toxin-producing bacteria such as Vibrio cholerae and enterotoxigenic Escherichia coli appears to depend largely on SIgA, and so does herd protection against horizontal faecal–oral spread of enteric pathogens under naïve or immunized conditions—with a substantial innate impact both on cross-reactivity and memory. Like natural infections, live mucosal vaccines or adequate combinations of non-replicating vaccines and mucosal adjuvants, give rise not only to SIgA antibodies but also to longstanding serum IgG and IgA responses. However, there is considerably disparity with regard to migration of memory/effector cells from mucosal inductive sites to secretory effector sites and systemic immune organs. Also, although immunological memory is generated after mucosal priming, this may be masked by a self-limiting response protecting the inductive lymphoid tissue in the gut. The intranasal route of vaccine application targeting nasopharynx-associated lymphoid tissue may be more advantageous for certain infections, but only if successful stimulation is achieved without the use of toxic adjuvants that might reach the central nervous system. The degree of protection obtained after mucosal vaccination ranges from reduction of symptoms to complete inhibition of re-infection. In this scenario, it is often difficult to determine the relative importance of SIgA versus serum antibodies, but infection models in knockout mice strongly support the notion that SIgA exerts a decisive role in protection and cross-protection against a variety of infectious agents. Nevertheless, relatively few mucosal vaccines have been approved for human use, and more basic work is needed in vaccine and adjuvant design, including particulate or live-vectored combinations. [Copyright &y& Elsevier]

Traditionally, the function of immunoglobulins A (IgA), the major type of secreted antibodies, has been thought to be restricted to binding antigens outside the epithelium basal membrane. Therefore, effector mechanisms eliminating IgA-opsonized targets have not been investigated so far. However, some indirect observations of infectious agents penetrating into tissues and blood from the environment suggest such mechanisms (analogous to IgG/IgM-dependent activation of complement and natural killers). In the present review, we examine details of IgA structure that might contribute to elucidation of IgA-dependent effector functions in human and animal immunity. Special attention is given to a putative transduction of signal about antigen binding in the active center of IgA from the Fab-to the Fc-superdomain via intramolecular conformational rearrangements. Different structure of the IgA subclasses (IgA1 and IgA2) is examined taking into account probable divergence of their functions in immune response. [ABSTRACT FROM AUTHOR]

Aerial emissions from a swine house at North Carolina State University's field laboratory were diluted to a level that could occur at varying distances downwind from a confined animal feeding operation (CAFO) both within and beyond the property line, and these emissions were delivered to an environmental exposure chamber. The study design consisted of two 1-hr sessions, one in which 48 healthy human adult volunteers were exposed to diluted swine air and another in which they were exposed to clean air (control). Objective measures of blood pressure, temperature, heart rate, respiratory rate, lung function, nasal inflammation, secretory immunity, mood, attention, and memory were correlated with objective measures of air quality. Ratings of perceived (self-reported) health symptoms were also obtained. The mean levels of airborne constituents in the swine air condition were hydrogen sulfide (24 ppb), ammonia (817 ppb), total suspended particulates (0.0241 mg/m³), endotoxin (7.40 endotoxin units/m³), and odor (57 times above odor threshold). No statistical differences on objective measures of physical symptoms, mood, or attention resulted from the 1-hr exposure to swine emissions in the environmental chamber when compared with clean air for healthy human volunteers. However, subjects were 4.1 (p = 0.001) times more likely to report headaches, 6.1 (p = 0.004) times more likely to report eye irritation, and 7.8 (p = 0.014) times more likely to report nausea in the swine air (experimental) condition than in the control condition. These results indicate that short-term exposure in an environmental chamber to malodorous emissions from a swine house at levels expected downwind can induce clinically important symptoms in healthy human volunteers. [ABSTRACT FROM AUTHOR]

This brief review describes mechanisms for acquired anti-microbial defence in the upper airways originating from active export of secretory immunoglobulin A and IgM, as well as epithelial leakage of serum-derived or locally produced IgG. Evidence is presented for regionalization of mucosal immunity in the upper airways, directed by a preferential profile of adhesion molecules and chemokine receptors expressed on B cells induced in mucosa-associated lymphoid tissue of Waldeyer''s ring, especially the palatine tonsils and adenoids, which differs from that imprinted on B cells in gut-associated lymphoid tissue. The possibility is also discussed that allergy is more common in the airways than in the gut because of differences in mucosally induced tolerance mechanisms. The nature of the mucosal epithelium, as well as functional properties of intra- or subepithelial dendritic cells and macrophages, may contribute to less robust local immune tolerance in the respiratory tract. [Copyright &y& Elsevier]

The lymphoid tissue of Waldeyer''s ring, and particularly the nasopharyngeal tonsil (adenoids), appears to be functionally comparable to nasal-associated lymphoid tissue in rodents. Antigen-stimulated lymphoid follicles give rise to: (a) clonal B-cell expansion; (b) B-cell receptor affinity maturation; (c) positive selection of B cells according to receptor affinity for antigen; (d) differentiation to B memory cells and plasma cells; and (e) variable induction of the joining (J)-chain gene. B-cell differentiation is also important to promote downstream isotype switching of the immunoglobulin (Ig) heavy chain constant genes. For tonsillar B cells, this process gives rise mainly to IgG and IgA plasma cells, partially associated with J-chain expression. Because the J chain is a key peptide in the polymer structure of secretory IgA, tonsils and adenoids may provide B cells for mucosal effector sites. Thus, several observations suggest that these lymphoid organs generate polymeric IgA (pIgA)-expressing B cells that migrate to the upper airway mucosa, lacrimal glands and salivary glands. Accordingly, the nasal route of vaccination induces secretory IgA-dependent regional mucosal immunity and will also enhance systemic immunity. Although the pIgA-producing capacity of tonsillar B cells is considerably decreased in children with recurrent tonsillitis, a conservative attitude towards adenotonsillectomy appears immunologically desirable, particularly in the young age group. [Copyright &y& Elsevier]

Objective: To compare secretory immunity in cecal and ileal orthotopic neobladders, and to detect its permanence over time. Patients and Methods: IgA was studied in the urine of 33 patients with ileocecourethrostomy (ICUS) and 13 patients with ileal reservoir (IR). The mean follow-up was 55 months. Results were compared in terms of the type of operation, a healthy control group, and the time since surgery. Results: Urinary IgA levels were significantly higher in ICUS and IR patients than in normal controls. No significant differences in IgA concentrations were detected in patients with different reservoirs and with regard to time. Conclusion: Both the reservoirs maintain the function of producing IgA. In particular no differences were detected over time and urine could be a permanent antigenic stimulus. IgA could be considered an adjunctive factor for upper urinary tract protection. For this reason we prefer to use a simple, indirect antireflux mechanism, thus avoiding direct manipulation of the uretero-intestinal anastomosis.Copyright © 2001 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The gastrointestinal immune system has evolved under the dual evolutionary pressure of preventing bacterial invasion along its extensive epithelial surfaces, while permitting absorption of nutrients. Accordingly, the development, selection and function of mucosal immune cells differ from comparable characteristics of lymphoid cells in other peripheral tissues. In the normal state, intestinal immune responses are aiming at exclusion of antigens - that is, preventing translocation of intestinal microorganisms and dangerous immunogenic substances such as bacterial toxins into the lamina propria. Furthermore, presentation of soluble food proteins and components of the autologous intestinal microflora to mucosal T and B cells, apparently results in immunological downregulation as well as active suppression of systemic immune responses, a phenomenon termed mucosal or 'oral' tolerance. The normal microbial flora has a major impact on the pool size, composition, antigen recognition repertoire, and effector function of mucosal immune cells. Local antibody responses are characterized by differentiation of B lymphocytes to lamina propria plasma cells which produce polymeric immunoglobulins, a process strictly regulated by mucosal T cells. Polymeric immunoglobulins (e.g., dimeric IgA and pentameric IgM) are actively transported by a specific receptor across the epithelial barrier into the gut lumen where they can bind bacteria and soluble antigens, thereby preventing them from adhering to, and penetrating, the mucosal surface. A major population of intestinal T cells is located in the surface epithelium, thus being strategically situated at the interface between the gut lumen and the interior of the body. However, their precise role in microbial defence has not yet been established. It is remarkable how the immune system normally maintains the balance between exclusion of (but coexistence with) the commensal gut bacteria, while protecting against (and eventually eliminating) intestinal pathogens. This immune balance appears to be tightly regulated by intestinal T cells. Recent findings in various genetically manipulated mouse models suggest that a dysregulated T-cell response against the normal intestinal microflora may lead to progressive inflammatory disease in the gut. This adverse development appears to reflect abrogation of oral tolerance and may be a central mechanism in the pathogenesis of inflammatory bowel disease. Also the development of atopic allergy appears to be influenced by immunoregulatory mechanisms on which the intestinal microflora exerts a substantial impact in terms of both mucosal barrier maintenance, oral tolerance and a balanced cytokine profile. [ABSTRACT FROM AUTHOR]

Five patients on continuous ambulatory peritoneal dialysis (CAPD) were immunized intraperitoneally with tetanus toxoid (TT) through an indwelling catheter. Four control patients on CAPD received the same dose of TT intramuscularly. Before immunization, virtually no anti-TT antibody secreting cells (AbSC) were detected by the enzyme-linked immunospot (ELISPOT) assay in pheripheral blood or peritoneal fluid from patients of either group. One to 2 weeks after immunization, high frequencies of TT-specific AbSC were detected in the circulation and peritoneal cavity. More than 80% of those cells were of the IgG isotype, with IgA accounting for most of the remainder. Patients receiving TT by the i.p. route showed significantly higher frequencies of specific IgG and IgA AbSC in the peritoneal cavity than patients immunized intramuscularly. Frequencies of AbSC in peripheral blood did not significantly differ between the two groups. Immunization with TT by both routes resulted in a significant increase of IgG anti-TT antibodies in serum, saliva and peritoneal fluid. A significant IgA antibody response was seen only in serum and peritoneal effluents. Therefore, i.p. immunization of human subjects with TT elicited both a localized response in the peritoneal cavity as well as a systemic response in serum, but did not induce a salivary IgA response. [ABSTRACT FROM AUTHOR]

Immune characteristics of intestinal metaplasia of the stomach were analyzed by the immunoperoxidase technique in frozen and paraffin-embedded specimens. In fetal and minimally inflamed adult gastric mucosa, secretory component (SC) was absent from epithelial cells. Non-intestinalized gastric mucosa with evident inflammatory changes showed weak SC immunoreactivity at the generative cell zone. Enhanced immunoreactivity of SC with evidence of transepithelial transport of IgA and IgM, but not of IgG, was demonstrated in intestinalized glands of either the complete or incomplete type. The number of inflammatory cells and lymphoid follicles was decreased in intestinalized mucosa when compared with that in non-intestinalized gastritic mucosa; J chain-negative IgG plasma cells and T cells, both of which were fairly abundant in the latter mucosa, were remarkably decreased in the former mucosa, whereas the decrease of J chain-positive IgA or IgM plasma cells was slight or equivocal. In either mucosa, IgA was the most popular immunoglobulin class in plasma cells. IgD plasma cells were very rare. In the germinal centers of lymphoid follicles which were preferentially distributed in non-intestinalized gastritic mucosa, IgM or IgG germinocytes predominated over IgA germinocytes, and a few T cells and NK cells also were present. Intraepithelial lymphoid cells with a T-suppressor phenotype were detected in intestinalized glands. The possibility that intestinal metaplasia is an adaptation to long-standing chronic gastritis is discussed. [ABSTRACT FROM AUTHOR]

Salivary SIgA antibodies against RS virus were studied in 105 children during the first year of life. The infants were divided into groups according to their risk of atopy. At birth 13 neonates showed measurable amounts of SIgA to RS virus. In another 26 children specific antibodies were detected but in concentrations too low for quantitative analysis. During the first year of life this increased to 29 antibody-positive Samples with measurable amounts of antibody and 39 with concentrations too low for quantitative determination. At this time 8 children of the high risk group had developed symptoms of allergy. None of these children had measurable amounts of SIgA anti-RSV in their saliva. In comparison, 10 of the remaining 26 high risk infants without symptoms of allergy did have such antibodies. Atopic infants had significantly more respiratory infections during the first year of life than nonatopic infants. The avidity of SIgA anti-RSV in neonatal samples was significantly higher than avidity determined in breast milk SIgA but comparable to the avidity of serum IgG. During the first year of life a continuing decrease of salivary SIgA avidity was observed. [ABSTRACT FROM AUTHOR]

Elevation of salivary SIgA-anti-casein has been shown to occur in newborn infants at risk of allergy. The present study was designed to follow 158 infants over 3 years to relate the onset of clinical disease to SIgA levels at birth. Newborn infants were divided into 3 groups according to their risk of allergy: Group I, (n = 62; no allergy risk); Group 11, (n = 30; low allergy risk); Group 111 (n = 66; high risk group). The groups were matched for smoking, social background, sex, and dietary habits of the patients. SIgA-anti-casein was determined by a direct ELISA. During the first year 59 infants developed atopic diseases (n = 37 of Groups I and 11; II = 22 of Group 111). After 3 years 37/61 infants of the high risk group had developed allergic symptoms. The frequency of atopic disease correlated with increased salivary antibody titers at birth (p < 0.05). 54% of infants with antibody titers > 250 EU/ml developed atopic symptoms at 1 year, 76% high risk infants with this titer developed atopic symptoms at 3 years of age. This study provides evidence that elevation of SIgA-anti-casein at birth not only reflects atopic risk as defined by cord blood IgE or family history, but correlates with the actual development of allergic disease during the first 3 years of life. [ABSTRACT FROM AUTHOR]

The mucosae form a barrier between our bodies and a hostile external environment. Diseases and extrinsic factors which impair mucosal function may lead to serious consequences. The mucosal immune system is the primary mediator of specific immunity at mucosal surfaces. As such, it is responsible for maintaining homeostasis and for defense against both overt and opportunistic pathogens. For this reason, it is also the target of many new vaccine strategies for the induction of mucosal immunity. This brief review will examine the mucosal immune system, its role in maintaining the integrity of the mucosa, and some of the strategies aimed at enhancing specific immunity. [ABSTRACT FROM AUTHOR]

Aim: To study the effect of the use of probiotics on the state of mucosal immunity in patients with type 2 diabetes. Evaluation of the results was carried out based on immunological parameters of the saliva of 50 patients suffering from type 2 diabetes with moderate periodontitis, before and 1 month after taking a probiotic complex based on Lactobacillus. In the salivary fluid of patients, a decrease in the concentration of pro-inflammatory cytokines IL-1β, TNF-α and IL-8 was noted, while an increase in the anti-inflammatory cytokine IL-10 was observed. An increase in local mucosal immunity was also observed, manifested in an increase in the synthesis of secretory immunoglobulin A.