Influence of allergens on human monocyte-derived dendritic cells

DCs spielen eine wesentliche Rolle bei der Induktion und Regulierung der adaptiven Immunantwort über die Antigenerkennung und Präsentation an naive T-Zellen, um sie zu T-Helferzellen (Th) zu polarisieren. Internalisierung und endozytotischer Abbau von Antigenen durch DCs sind wichtige Schritte für das T-Zell Priming. Diese Studie beschäftigte sich mit der Frage, ob unterschiedliche Allergene die zelluläre Aufnahme von MoDCs und das anschließende T-Zell Priming beeinflussen. Von polysensibilisierten PatientInnen wurden MoDCs wurden benutzt für anschließend wurde die Expression von Oberflächenmarkern der MoDCs, die Proliferation und das Zytokinprofil von autologen naiven T-Zellen nach erfolgter Kokultur mit Allergen stimulierten MoDCs analysiert. In dieser Studie wurde die Th2-Polarisierung nach Allergenstimulierung nur dann nachgewiesen, wenn der Spender ein positives Sensibilisierungsprofil hatte. Die unteschiedliche Kapazität der DCs naive T Zellen zu polarisieren könnte auf der individuellen Prozessierung der Allergene und anschließender Antigenpräsentation der DCs beruhen. Daher wurde ein in vitro Modell entwickelt, um die Bindung der Allergene an die Zelloberfläche und anschließende Prozessierung zu untersuchen. Es konnten jedoch weder qualitative noch quantitative Unterschiede gefunden werden. Die Aufnahme der unterschiedlichen Allergene erfolgt anscheinend über allgemeine Aufnahmemechanismen, und dürfte auf den polarisierenden Effekt der DCs keinen Einfluss haben. Ebenso scheint der Sensibilisierungsstatus des Spenders keinen Einfluss auf die Allergenaufnahme und Prozessierung zu haben. Diese Art von Studien kann dazu beitragen unser Verständnis über die Entstehung einer allergischen Immunantwort zu vertiefen und die wichtigen Faktoren zu identifizieren, die diese fehlgeleiteten Reaktionen verursachen und steuern. Erst dann können wirkungsvolle Strategien für die Prävention einerseits und für die Therapie anderseits entwickelt werden.Dendritic cells (DCs) play an essential role in the induction and regulation of the adaptive immune response via antigen recognition and presentation to naïve T cells in order to polarize T helper (Th) cells. Internalization and endocytic degradation of antigens by DCs are important steps required for T cell priming. This study was designed to produce more detailed information about the initiation of IgE-mediated hypersensitivity through investigating the influence of several allergens on allergen uptake and T cell priming by DCs. Monocyte derived dendritic cells (MoDCs) obtained from polysensitized allergic patients were used to evaluate surface marker expression in MoDCs, proliferation and cytokine profiles of activated naïve T cells with allergen pulsed MoDCs. MoDCs were tested for surface binding and internalization of the allergens and simultaneous binding and uptake of the two allergens were tested in a competitive assay with mixed allergens. In this study, Th2 polarizing was only observed in cells stimulated with the allergen to which the patients were sensitized. No qualitative and quantitative differences in the allergen uptake of both, Phl p 5 and SF-nsLTP were detected in single and competitive assays. However, simultaneous uptake of these allergens can propose a common pathway initiated by surface receptors or other mechanisms in MoDCs which are unable to distinguish specific versus non-specific allergen in both, allergic and non-allergic individuals. These studies contribute to the development of methods to manipulate the immune system to identify interventional strategies to control allergic diseases at the earliest stages.submitted by Kazem AshjaeiAbweichender Titel laut Übersetzung der Verfasserin/des VerfassersZsfassung in dt. SpracheWien, Med. Univ., Diss., 2015OeBB(VLID)171520

Maternity and child health care services delivered by public health centers compared to health cooperatives: Iran's experience

Reform programs in some developing countries are focused in transferring these services to nongovernmental organizations or groups. In this WHO grant study our aim was to implement and evaluate the efficacy of a new model for transferring state service delivery governance to nongovernmental groups and studying if they can be efficient in field of child and maternity health services compared to public health centers. In this comparative study a total of 1000 households were selected systematically from the population covered by 9 health centers transferred to cooperatives and 18 current public health centers. Data were collected during a three months long study period and analyzed by SPSS 10 statistical package. Chi-Square and t-tests were used to analyze data. Overall health care coverage was higher for either cooperative or public health centers compared to private sector physicians (p = 0.005). Around 88.8% of under 6 years aged children were under coverage of health services provided by health centers in both groups and no difference was found. There was no statistically significant difference in quality of child health care services in declaring the date of health care visit and follow up in due time. There was no difference between the groups in perfect filling child growth cards but the ability of mothers in interpreting child growth cards was statistically higher for the population covered by cooperative health centers (p = 0.02). Growth status of children based on growth percentiles were relatively similar in two groups. Some health indices of target groups covered by public and cooperative health centers such as family planning, child health cares, perinatal cares, and the numbers of households covered by health volunteers were studied. The results showed that in all of these fields cooperative health centers had better rates. Observed differences were statistically significant (family planning: p = 0.03, infant health care: p = 0.03, 1-6 years old children cares: p = 0.009). The proportion of those women owning a vaccination record (card) was higher in population covered by cooperative health centers (p = 0.004). The rate for performing a cervical smear examination during the national program for cervical cancer screening was higher for the women covered by cooperative health centers (p = 0.01). No difference was found between the knowledge level of women covered by cooperative health centers about the importance of cervical examination when compared with public health centers. We conclude that in the field of target group children's health care and maternity health services, cooperatives sector not only acts as well as public sector meeting the standards of the program, but also has got a better function in some areas. This can be assumed as an achievement for the policy of transferring the health services to cooperative health centers along with ongoing governmental supervision

Atopic donor status does not influence the uptake of the major grass pollen allergen, Phl p 5, by dendritic cells

AbstractDendritic cells (DCs) are sentinels of the immune system for antigen recognition and uptake, as well as presentation to naïve T cells for stimulation or priming. Internalization and endocytic degradation of allergens by DCs are important steps required for T cell priming.In the current study we investigated binding and internalization of purified recombinant non-glycosylated grass pollen allergen, Phl p 5, and natural non-specific lipid transfer protein from sunflower, SF-nsLTP to human monocyte derived dendritic cells (MoDCs). Colocalization of Phl p 5 with low affinity (CD23) or high affinity receptor (FcεRI) was investigated by immunofluorescence staining. Likewise, localization of the allergens in early (EE) and late endosomes (LE) was detected by co-staining for early endosome antigen (EEA1) and lysosomal-associated membrane protein 1 (LAMP1).In our experimental setting we could demonstrate that Phl p 5 as well as SF-nsLTP bound to MoDCs from both, grass pollen allergic and non-allergic individuals. Competitive allergen uptake experiments demonstrated non-preferential and simultaneous uptake of Phl p 5 and SF-nsLTP by MoDCs. No overlap of signals from Phl p 5 and CD23 or FcεRI was detectable, excluding IgE-mediated uptake for this allergen. Both allergens, Phl p 5 and SF-nsLTP, were localized in early and late endosomes.The present study applied a set of methods to assess the allergen uptake by MoDCs in an in vitro model. No qualitative and quantitative differences in the allergen uptake of both, Phl p 5 and SF-nsLTP were detected in single and competitive assays