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Background Nonessential allergy diets in children with mild symptoms may harm the development of immunological tolerance and impose a burden on families and day care. We aimed to reduce the high prevalence of allergy diets in day care by reforming the practices for inquiring about need of special diets from parents. Methods We developed a new special diet form and an information leaflet based on the new allergy guidelines. The new form was implemented into 40 Finnish day care centres in the capital region in 2013-2015. The questionnaires on practices concerning special diets in day care centres and allergy knowledge were collected from the personnel. Results After 2 years, the new special diet form was used by 64% of families with food-allergic children, and the prevalence of allergy diets in day care centres decreased by 43% to 4.3% ( IQ range 3.05-5.96). A significant decrease was found in the prevalence of all basic (milk, grains, egg) and most other allergy diets ( P for trend < 0.01). The new practice was well accepted by day care and kitchen personnel. Lack of updated allergy knowledge was noted among day care personnel. Conclusions The burden of allergy diets in day care settings could be decreased by simple pragmatic changes based on current allergy guidelines. Old allergy attitudes persisted among day care personnel, indicating the need for continuous education. [ABSTRACT FROM AUTHOR]

Background: In early childhood, the ability to mount protective immune responses in the airways is impaired, with increased risk of allergic sensitisation to inhaled allergens. Antigen presenting cells (APC) and regulatory T cells (Treg) are important modifiers of T cell immunity but little is known about their distribution in bronchial mucosa at this age. Here the subset distribution of APC and the appearance of Foxp3+ Treg and bronchus associated lymphoid tissue (BALT) were examined immunohistochemically in children less than 2 years of age with chronic asthma-like symptoms of the lower airways. Methods: mmunophenotyping was performed in situ on bronchial biopsy specimens obtained from 45 infants, 4-23 months of age, under investigation for airway disease. Results: A well developed HLA-DR+ network of APC was present in all samples, approximately 50% of the cells being CD68+ macrophages and the remainder various subsets of dendritic cells. The density of HLA-DR+ cells increased significantly with age but was not related to atopy, clinical symptoms or lung function. Comparing the density of APC subsets and clinical parameters, only the number of intraepithelial CD1a+ dendritic cells was significantly increased in infants who had recently suffered a respiratory infection. BALT structures were identified in 22 children, with no relation to lung function, atopic status or human rhinovirus positivity. Plasmacytoid dendritic cells and Foxp3+ Treg were located primarily within these isolated lymphoid follicles. Conclusion: A bronchial network of dendritic cells and macrophages develops quite rapidly after birth, apparently independent of clinical symptoms or atopy. The high frequency of BALT structures containing putative tolerogenic dendritic cells and Treg suggests that these lymphoid follicles play an important role in bronchial immune homeostasis during infancy. [ABSTRACT FROM AUTHOR]

T lines specific for measles virus (MV) were generated from blood of two DR1/DR2 heterozygous healthy donors with a history of past measles infection. The antigenic specificity of 66 T cell clones derived from the lines was studied in a blastogenic assay using whole measles virus and two purified virus components, haemagglutinin and nucleocapsid. Thirty-nine of the clones were specific for one of the two purified antigens. None of seven synthetic peptides covering 20% of the MV haemagglutinin amino acid sequence stimulated T cell clones with haemagglutinin specificity. Responsiveness of the majority of the clones were restricted by HLA-D/DR antigens, although two clones were isolated that responded only to MV antigens presented by autologous cells. Ten of 11 clones recognizing the nucleocapsid antigen were DR1-restricted, while the haemagglutinin antigen and whole measles virions were recognized more often in association with the DR2 antigen. These results indicate that much of the MV-specific memory T cell response is specific for the haemagglutinin and nucleocapsid virus antigens, with the DR antigen being the main restriction element involved. [ABSTRACT FROM AUTHOR]

he ability of 17 monoclonal antibodies (MoAb) against measles virus haemagglutinin (MV-H) to bind to 10 selected MV-H-specific synthetic peptides was tested in an enzyme immunoassay (EIA). Three peptides representing residues 126-135 (close to the NH; terminus). 309-318 (middle), and 587-596 (C-terminal) reacted with MoAb designated 48, 129. and 18. respectively. Binding of MoAb 129 to purified virus was abolished after pre-incubation with the peptide 309- 318. Similarly. MoAb 48 did not bind to the virus after absorption with the peptide 126-135. Longer peptides of 19 residues from the regions reacting with the MoAb were also synthesized and tested in FIA. None of the MoAb recognized these longer peptides when the latter were bound as free peptides on solid phase. However. MoAb 129 binding to purified virus was blocked equally well by peptides 304 322 and 309 318, In contrast. peptide 121 139 absorbed the reactivity of the MoAb 48 much more weakly than the shorter peptide 126-135. suggesting that the conformation of the longer peptide in solution is different. To analyse affinities in the antigen - antibody reactions, the plates were washed with buffers of varying pH after absorption of the MoAb 10 MV or peptides. The MoAb 129 bound both to MV and peptide 309-318 with equal affinity. but MoAb 48 and 18 bound to the peptides 126-135 and 587 596 with lower affinity than to the virus. This study indicates that regions corresponding to ammo acids 126-135. 309-318, and 587-596 define antigenic sites of the H protein. [ABSTRACT FROM AUTHOR]

BALB/c mice were pretreated with cyclophosphamide and immunized 2 days later with inactivated, purified measles virus (MV) mixed with dimethyl dioctadecyl ammonium bromide (DDA). Seven days later, lymph nodes (LN) were removed and lymphocytes cultured in the presence of purified MV antigens. MV haemagglutinin (H) was found to be a major antigen responsible for proliferation of the lymphocytes. Incorporation of purified H into liposomes significantly enhanced the proliferative response compared with purified H alone. Response to MV nucleocapsid protein was only moderate, and insertion of this protein into liposomes did not improve the response. As an attempt to analyse T-cell epitopes of MVH, three synthetic peptides previously found to elicit a strong antibody response were used both as priming and stimulating antigens. None of the peptides was able lo elicit a secondary response when MV-primed LN cells were stimulated in vitro. However, each peptide primed T cells for a secondary challenge with purified, inactivated MV, which was demonstrated by proliferation and a delayed-type hypersensitivity assay and also by transfer experiments with peptide-primed cells. [ABSTRACT FROM AUTHOR]

The recent outbreak of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), has led to a worldwide pandemic. One week after initial symptoms develop, a subset of patients progresses to severe disease, with high mortality and limited treatment options. To design novel interventions aimed at preventing spread of the virus and reducing progression to severe disease, detailed knowledge of the cell types and regulating factors driving cellular entry is urgently needed. Here we assess the expression patterns in genes required for COVID-19 entry into cells and replication, and their regulation by genetic, epigenetic and environmental factors, throughout the respiratory tract using samples collected from the upper (nasal) and lower airways (bronchi). Matched samples from the upper and lower airways show a clear increased expression of these genes in the nose compared to the bronchi and parenchyma. Cellular deconvolution indicates a clear association of these genes with the proportion of secretory epithelial cells. Smoking status was found to increase the majority of COVID-19 related genes including ACE2 and TMPRSS2 but only in the lower airways, which was associated with a significant increase in the predicted proportion of goblet cells in bronchial samples of current smokers. Both acute and second hand smoke were found to increase ACE2 expression in the bronchus. Inhaled corticosteroids decrease ACE2 expression in the lower airways. No significant effect of genetics on ACE2 expression was observed, but a strong association of DNA- methylation with ACE2 and TMPRSS2- mRNA expression was identified in the bronchus.

Increased airway responsiveness (AR) is one of the main pathophysiological manifestations of asthma. The present study aimed to define the clinical features associated with increased AR in infants with recurrent lower respiratory tract symptoms. AR was evaluated by performing a novel dosimetric methacholine challenge test. Increased AR to methacholine, defined as a methacholine dose of < or =0.90 mg producing a 40% fall (PD(40)) in the maximal flow at functional residual capacity (V'(max,FRC)), was associated with atopy (odds ratio (OR) 4.1; 95% confidence interval (CI) 1.3-13.3), a history of physician-confirmed wheezing with respiratory syncytial virus (OR 32.9; 95% CI 2.5-428.8) or of a nonspecified aetiology (OR 4.9; 95% CI 1.1-22.5), functional residual capacity z-score > or =2 (OR 36.8; 95% CI 2.9-472.6), and V'(max,FRC) z-score (OR 0.5; 95% CI 0.2-0.9) at baseline, when compared with infants with only mild or no responsiveness to methacholine (PD(40) V'(max,FRC) >0.90 mg). In conclusion, in recurrently symptomatic infants, increased airway responsiveness is associated with reduced baseline lung function, an atopic trait of the child, a history of physician-confirmed wheeze and viral aetiology of wheeze. Future intervention studies are needed to confirm the role of airway responsiveness in respiratory morbidity during infancy.