The house dust mite, Dermatophagoides farinae, was fractionated by a Sephadex G-200 column. Its allergenic (IgE-reacting) and immunogenic (IgG-reacting) components were investigated. By means of skin test, the molecular weight (MW) of major allergenic components of mite was found to be approximately 9,000 to 21,000 daltons. Immunogenic components were investigated by enzyme linked immunosorbent assay using each fraction as an antigen and mice plasma and human serum as antibodies. With mouse plasma, high IgG antibody titers were observed in fractions that contained the part of the mite with high MW (greater than 150,000). With human sera, high IgG antibody titers were observed in fractions that contained the part of the mite with MW more than 30,000. Heterogeneity of human IgG antibody responses against mite antigen was also suggested.
CD26 truncates several chemokines as well as neuropeptides and influences immune responses via modulation of cell adhesion and T cell activation, suggesting an involvement of CD26 in asthmatic and airway inflammation. Therefore, Fischer 344 (F344), Brown Norway (BN) and Lewis (LEW) rat strains, which differ in their CD26-like enzymatic activity, were compared using an asthma model. Additionally, two CD26-deficient mutant F344 rat substrains were included and compared to the wild-type F344 substrain. Immunization was performed twice with ovalbumin (OVA), and 2 weeks later the rats were challenged with OVA intratracheally Flow cytometry (FACS) analysis of different leucocyte subsets as well as enzyme-linked immunosorbent assay (ELISA) for IgE levels in the blood and bronchoalveolar lavage (BAL) were performed 24 h after challenge. LEW rats with the lowest CD26 activity among the rat strains investigated here displayed significantly reduced CD4+ T cell numbers in the BAL compared to wild-type F344 and BN rats. Moreover, in asthma, the ratio of CD26+ to CD26- T cell receptor (TCR)-positive cells increased significantly in F344 and LEW but not BN rats. Most intriguingly, in both CD26-deficient F344 rat substrains the number of CD4+ T lymphocytes was markedly reduced compared to wild-type F344. The decrease in T cell recruitment observed in the CD26-deficient rats was associated with significantly reduced OVA-specific IgE-titres. This is the first report to show a remarkably reduced T cell recruitment in rat strains that either lack or exhibit reduced CD26-like enzymatic activity, suggesting a role for CD26 in the pathogenesis of asthma via T cell-dependent processes such as antibody production.
We studied the relationship of serum levels of IgA and IgE to allergic manifestations and otitis media in a cohort of 179 Icelandic children, aged 18 to 23 months. Only one of the infants had IgA deficiency (less than 50 micrograms/ml); all the others had IgA levels that were normal for their age. The children were divided into three groups according to their IgA levels (lowest 25%, intermediate 50%, highest 25%) and the clinical findings analyzed accordingly. The cumulative incidence of definite allergic manifestations was 37%. Asthma and otitis media were significantly more common among the infants with low normal IgA levels than among those with intermediate to high IgA levels. There was also a significant association between the severity of allergic manifestations and low IgA levels (p = 0.002). Children with detectable IgE (greater than or equal to 0.23 kilounit/L) had a higher incidence of atopic manifestations than did children in whom IgE was not detectable, but only a weak correlation was found between the occurrence and extent of allergic symptoms and increasing amounts of IgE beyond the 0.23 kilounit/L level. These findings suggest that atopic manifestations in infants may be more dependent on delayed maturation of IgA production than on overproduction of IgE.
A total of 100 children with bronchopulmonary diseases were examined. Of these, in 80 bronchial asthma and in 20 children acute pneumonia were diagnosed. The deficiency of local cell mediated and humoral factors on the mucous membranes of the upper respiratory tracts was established. In the squamous and columnar epithelium cells an increased destruction and cytolysis was noted leading to disturbances in the integrity of the protective barrier of the epithelial cover. In addition, this study revealed the deficiency of neutrophilic leukocytes, pronounced local eosinophilia and the low level of humoral protective factors. In acute pneumonia an increase in the amount of neutrophilic leukocytes in the secretion of the nasal cavity together with the appearance of destructive processes in epithelial cells took place. Pronounced deficiency in serum IgA and IgG was accompanied by compensatory increase in secretory IgA.
Patients with eosinophilic variant of bronchial asthma demonstrate high levels of fibrinolytic activity in their bronchial secretion along with low content in same of Ig A, as evidenced by findings obtained in the course of sanatorium treatment. There is usually no correlation between the above changes and routine methods of health resort treatment. The judicious employment in a complex of therapeutic measures of aerosols of hydrocarbonate of sodium and heparin promotes neutralization of cationic proteins and large major protein of eosinophiles in the bronchial lumen whereby there occurs normalization of Ig A levels in the sputum along with lowering of its fibrinolytic activity.
Study of the interferon system (IFN) and the production of major cytokines in patients with bronchial asthma of various course severity.
204 patients with atopic bronchial asthma (BA); 32 patients with allergic rhinitis (AR) and 93 mostly healthy volunteers were examined. Blood cells of patients with BA of various course severity were studied by biological method in HEP cell culture for the ability to produce IFN. Levels of cytokines in the blood sera were determined by EIA method with the corresponding commercial test systems: IL-4, IL-10, IL-13 and IFN-gamma according to user manual.
Disorders in the ability ofleukocytes to produce IFN-alpha and IFN-gamma were detected in patients with bronchial asthma and allergic rhinitis. Misbalance in the production of pro- and anti-inflammatory cytokines depending on the level of disease severity was noted. The highest serum IFN-gamma was noticed in patients with mild persistence BA course, that is most probably determined by higher frequency of ARVI in this group of patients. Maximum level of IL-10 was detected in mild BA form and was nearly undetected in the severe course of the infection, which is characterized by higher content of IL-4 in blood sera.
Increase of course severity of chronic (allergic) inflammation in bronchial tissue and higher frequency of ARVI among patients with persistent BA of medium and severe course is characterized by a lack of interferon link of the immune system and disorders of regulatory mechanisms, that is expressed by a change in the ratio of IFN-gamma/IL-4 parameters and decrease of IL-10 content in blood sera.
To investigate the effect of aging on the allergic airway response, we examined the bronchoconstrictive responses and cellular inflammatory changes in a rat model of bronchial asthma by evaluating young and old animals. Two different age groups of Brown-Norway rats, actively sensitized by injection of ovalbumin into the foot pads, were used: 7 to 8 weeks old (young group) and 100 to 120 weeks old (aged group). Both the aged and young rats produced on ovalbumin-specific IgE antibody and exhibited an immediate asthmatic response after exposure to ovalbumin, but the degree of specific IgE antibody was significantly higher in young rats. The young group showed a marked increase in the number of eosinophils and neutrophils in bronchoalveolar lavage fluid 2 days after exposure to ovalbumin, whereas no eosinophilia was seen in the aged group. To evaluate the mechanism of the decreased accumulation of eosinophils in aged rats, cells from popliteal lymph nodes from ovalbumin-sensitized rats were incubated with ovalbumin for 48 hours. Although eosinophil chemotactic activity, determined by a modified Boyden chamber method, was present in the supernatant of cultured lymph node cells from young rats, it was absent from those of aged rats. In vivo administration of anti-IL-5 monoclonal antibody revealed that one of the factors of eosinophil chemotactic activity was IL-5. Lymph node cells from aged rats tended to produce greater amounts of interferon-gamma than did those from young animals. Findings indicate that aged rats have a defect in eosinophil accumulation in sites exposed to antigen, probably because of an age-dependent alteration in T cells.
Particle exposure is known to have negative health effects. In Stockholm the environment in the subway has been reported to have higher particle exposure levels, measured as PM(2.5) and PM(10), than roads with intense traffic in the inner city area. We have recently shown that healthy volunteers exposed to subway environment had statistically significant increase of fibrinogen and CD4 cells expressing regulatory T-cell marker CD25(bright)/FOXP3 in blood. The aim of the present study was to find out whether a more vulnerable population, asthmatics, would demonstrate similar or other changes in the lungs or in the peripheral blood. Sixteen mild asthmatics were exposed to a subway and a control environment for 2 h while being monitored by measurements of lung function, and inflammatory response in the lower airways evaluated by bronchoscopy and in peripheral blood. An attempt to standardize the exposures was done, by letting the volunteers alternate 15 min intervals of moderate exercise on a bicycle ergometer with 15 min of rest. We found a statistically significant increased frequency of CD4 cells expressing T-cell activation marker CD25 in bronchoalveolar lavage fluid, but no significant increase of regulatory T-cells in blood as was found in healthy volunteers. Our study shows that airway inflammatory responses after exposure in subway environment differ between asthmatic and healthy humans.
Lower socioeconomic status (SES) is consistently associated with poor health, yet little is known about the biological mechanisms underlying this inequality. In children, we examined the impact of early-life SES trajectories on the intensity of global innate immune activation, recognizing that excessive activation can be a precursor to inflammation and chronic disease.
Stimulated interleukin-6 production, a measure of immune responsiveness, was analyzed ex vivo for 267 Canadian schoolchildren from a 1995 birth cohort in Manitoba, Canada. Childhood SES trajectories were determined from parent-reported housing data using a longitudinal latent-class modeling technique. Multivariate regression was conducted with adjustment for potential confounders.
SES was inversely associated with innate immune responsiveness (p=0.003), with persistently low-SES children exhibiting responses more than twice as intense as their high-SES counterparts. Despite initially lower SES, responses from children experiencing increasing SES trajectories throughout childhood were indistinguishable from high-SES children. Low-SES effects were strongest among overweight children (p
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Cites: Proc Natl Acad Sci U S A. 2009 Aug 25;106(34):14716-2119617551
To examine the associations between selenium (Se) status, asthma, bronchial hyperresponsiveness (BHR), and atopy in 154 male subjects (72 with mild asthma, 41 with BHR and 41 with no respiratory symptoms) aged 18 (range 17-22) years. Each subject underwent a medical interview and FEV1 and FVC were recorded. Histamine bronchial reactivity (Yan method) was measured, skin prick test (inhalant allergens) was performed and Se in urine and serum was analysed (AOAC modified fluometric method). Se in serum 74.04 (10.58) micrograms/L (mean (SD)) was lower in subjects with asthma and the logarithm of the ratio of Se in serum (microgram/L) and urine standardised to creatinine excretion (ng/mg creatinine) 0.748 (0.096) (mean (SD)) was lower in subjects with asthma and atopy compared to subjects with no allergic symptoms 77.79 (10.16) micrograms/L and 0.808 (0.111) respectively (p