Different T cell memory in preadolescents after whole-cell or acellular pertussis vaccination.

To better understand vaccine-induced protection and its potential failure in light of recent whooping cough resurgence, we evaluated quantity as well as quality of memory T cell responses in B. pertussis-vaccinated preadolescent children. Using a technique based on flow cytometry to detect proliferation, cytokine production and phenotype of antigen-specific cells, we evaluated residual T cell memory in a cohort of preadolescents who received a whole-cell pertussis (wP; n=11) or an acellular pertussis vaccine (aP; n=13) during infancy, and with a median of 4 years elapsed from the last pertussis booster vaccine, which was aP for all children. We demonstrated that B. pertussis-specific memory T cells are detectable in the majority of preadolescent children several years after vaccination. CD4(+) and CD8(+) T cell proliferation in response to pertussis toxin and/or filamentous hemagglutinin was detected in 79% and 60% of the children respectively, and interferon-γ or tumor necrosis factor-α producing CD4(+) T cells were detected in 65% and 53% of the children respectively. Phenotyping of the responding cells showed that the majority of antigen-specific cells, whether defined by proliferation or cytokine production, were CD45RA(-)CCR7(-) effector memory T cells. Although the time since the last booster vaccine was significantly longer for wP-compared to aP-vaccinated children, their proliferation capacity in response to antigenic stimulation was comparable, and more children had a detectable cytokine response after wP- compared to aP-vaccination. This study supports at the immunological level recent epidemiological studies indicating that infant vaccination with wP induces longer lasting immunity than vaccination with aP-vaccines.

Cytokine and antibody profiles in 1-year-old children vaccinated with either acellular or whole-cell pertussis vaccine during infancy.

Two different types of pertussis vaccines are currently available to protect children against whooping cough, the first-generation whole-cell (Pw) vaccines and the more recent acellular (Pa) vaccines. Both types provide good protection, yet induce different types of immune responses in 6-month-old infants, with a strong Th1 response induced by Pw vaccines compared to a mixed Th1/Th2 response and a delay in non-specific IFN-gamma secretions after the administration of Pa vaccines. We show here that at 13 months of age, most Pw- or Pa-vaccinated children display Bordetella pertussis-specific T-cell responses, in addition to significant antibody levels, although a higher Th2/Th1 cytokine ratio remained in Pa recipients compared to Pw recipients. In contrast, the proportion of children with tetanus toxin-specific T-cell responses was lower in Pa than in Pw vaccine recipients, although most children had protective anti-tetanus toxin IgG levels. In addition, the global Th2 bias observed in 6-month-old infants vaccinated with a Pa vaccine was normalized at 13 months.

Bordetella pertussis from functional genomics to intranasal vaccination.

Whooping cough still represents a major health problem, despite the use of effective vaccines for several decades. Being classically a typical childhood disease, whooping cough in young adults is now more common than it used to be, suggesting that protection after vaccination wanes during adolescence. As an alternative to the current vaccines, we wish to develop live attenuated vaccines to be delivered by the nasal route, such as to mimic the natural route of infection and to induce long lasting immunity. Bordetella pertussis, the etiological agent of whooping cough, produces a number of virulence factors, including toxins. Its recently determined genome sequence makes it now possible to apply functional genomics, such as transcriptomics and systematic knock-out mutagenesis. The expression of most known B. pertussis virulence genes is controlled by the two-component system BvgA/S. DNA microarray analyses have led to the identification of novel genes in the BvgA/S regulon, some of which are activated by BvgA/S and others are repressed by BvgA/S. In addition, some genes appear to be differentially modulated by nicotinic acid and MgSO4, both known to modulate the expression of BvgA/S-regulated genes. Among others, the functional genomics approach has uncovered two strongly BvgA/S-activated genes, named hotA and hotB (for 'homolog of toxin'), the products of which show high sequence similarities to pertussis toxin subunits. The identification of the full array of virulence factors, as well as an integrated understanding of the bacterial physiology should allow us to design attenuated B. pertussis strains useful for intranasal vaccination. A first generation of attenuated strains has already shown full protection in mice after a single intranasal administration. Such strains may also serve as vaccine carriers for heterologous antigens, in order to vaccinate against several different pathogens simultaneously.

Age-related immune reconstitution during highly active antiretroviral therapy in human immunodeficiency virus type 1-infected children.

OBJECTIVES: To evaluate the immune reconstitution in HIV-1-infected children in whom highly active antiretroviral therapy (HAART) controlled viral replication and to assess the existence of a relation between the magnitude of this restoration and age. METHODS: All HIV-1-infected children in whom a new HAART decreased plasma viral load below 400 copies/ml after 3 months of therapy were prospectively enrolled in a study of their immune reconstitution. Viral load, lymphocyte phenotyping, determination of CD4+ and CD8+ T cell receptor repertoires and proliferative responses to mitogens and recall antigens were assessed every 3 months during 1 year. RESULTS: Nineteen children were evaluated. Naive and memory CD4+ percentages were already significantly increased after 3 months of HAART. In contrast to memory CD4+ percentages, naive CD4+ percentages continued to rise until 12 months. Age at baseline was inversely correlated with the magnitude of the rise in naive CD4+ cells after 3, 6 and 9 months of therapy but not after 12 months. Although memory and activated CD8+ cells were already decreasing after 3 months, abnormalities of the CD8 T cell receptor repertoire and activation of CD8+ cells persisted at 1 year. HAART increased the response to mitogens as early as 3 months after starting therapy. CONCLUSIONS: In children the recovery of naive CD4+ cells occurs more rapidly if treatment is started at a younger age, but after 1 year of viral replication control, patients of all ages have achieved the same level of restoration. Markers of chronic activation in CD8+ cells persist after 1 year of HAART.

Basophil activation tests for the diagnosis of food allergy in children.

BACKGROUND: Positive skin prick tests (SPT) for food allergens and specific IgE (sIgE) in serum indicate sensitization but do not enable distinction between sensitized but tolerant and clinically allergic patients. OBJECTIVE: Herein, we evaluate the clinical relevance of basophil activation tests (BATs) for peanut or egg allergy diagnosis. METHODS: Thirty-two peanut-allergic, 14 peanut-sensitized (sIgE(+) and/or SPT(+) to peanuts) but tolerant children and 29 controls with no history of an adverse reaction to peanuts were included. Similarly, 31 egg-allergic, 14 egg-sensitized children (sIgE(+) and/or SPT(+) to egg white) and 22 controls were studied. Flow cytometric analysis of CD63 expression or CD203c upregulation on basophils and the production of leukotrienes (LT) were performed in response to an in vitro crude peanut extract or ovalbumin (OVA) challenge. RESULTS: After in vitro peanut challenge, the basophils from peanut-allergic children showed significantly higher levels of activation than those from controls (P<0.001). After OVA challenge, a similar distinction (P<0.001) was observed between egg-allergics and controls. Interestingly, the majority of egg- or peanut-sensitized children failed to activate basophils, respectively, in response to OVA and peanut challenge. The sensitivity of the CD63, CD203c and LT assay was 86.7%, 89.5% and 76.0% with a specificity of 94.1%, 97.1% and 94.6% for peanut allergy diagnosis. The corresponding performances of BATs applied to egg allergy diagnosis were 88.9%, 62.5% and 77.8% for the sensitivity and 100%, 96.4% and 96.4% for the specificity. CONCLUSION: Neither conventional tests nor BATs are sensitive and specific enough to predict food allergy accurately. However, BATs may helpfully complete conventional tests, especially SPT, allowing improved discrimination between allergic and non-allergic individuals.

Helper T cell dysfunctions in a patient with Omenn's syndrome: modulation by IFN-gamma therapy.

Case Reports

Are the reference values of B cell subpopulations used in adults for classification of common variable immunodeficiencies appropriate for children?

Detailed phenotypic characterization of B cell subpopulations is of utmost importance for the diagnosis and management of humoral immunodeficiencies, as they are used for classification of common variable immunodeficiencies. Since age-specific reference values remain scarce in the literature, we analysed by flow cytometry the proportions and absolute values of total, memory, switched memory and CD21(-/low) B cells in blood samples from 168 healthy children (1 day to 18 years) with special attention to the different subpopulations of CD21(low) B cells. The percentages of total memory B cells and their subsets significantly increased up to 5-10 years. In contrast, the percentages of immature CD21(-) B cells and of immature transitional CD21(low)CD38(hi) B cells decreased progressively with age, whereas the percentage of CD21(low) CD38(low) B cells remained stable during childhood. Our data stress the importance of age-specific reference values for the correct interpretation of B cell subsets in children as a diagnostic tool in immunodeficiencies.

Both CD4+ and CD8+ lymphocytes participate in the IFN-y response to filamentous hemagglutinin from Bordetella pertussis in infants, children and adults

Infant CD4+ T-cell responses to bacterial infections or vaccines have been extensively studied, whereas studies on CD8 + T-cell responses focused mainly on viral and intracellular parasite infections. Here we investigated CD8 + T-cell responses upon Bordetella pertussis infection in infants, children, and adults and pertussis vaccination in infants. Filamentous hemagglutinin-specific IFN-γ secretion by circulating lymphocytes was blocked by anti-MHC-I or -MHC-II antibodies, suggesting that CD4 + and CD8 + T lymphocytes are involved in IFN-γ production. Flow cytometry analyses confirmed that both cell types synthesized antigen-specific IFN-γ, although CD4 + lymphocytes were the major source of this cytokine. IFN-γ synthesis by CD8 + cells was CD4 + T cell dependent, as evidenced by selective depletion experiments. Furthermore, IFN-γ synthesis by CD4 + cells was sometimes inhibited by CD8 + lymphocytes, suggesting the presence of CD8 + regulatory T cells. The role of this dual IFN-γ secretion by CD4 + and CD8 + T lymphocytes in pertussis remains to be investigated. © 2012 Violette Dirix et al.

Der Bildungsbericht 2011

Ziel des Bildungsberichts ist es, das Bildungsgeschehen und die Bildungswege von Kindern, Jugendlichen und jungen Erwachsenen in der Stadt Essen anhand der ausgewählten Indikatoren abzubilden. Damit soll zunächst für Essen die Frage beantwortet werden, ob und in welchem Maß der allgemein behauptete Zusammenhang von sozialer Herkunft und Bildungserfolg besteht, um dann identifizieren zu können, wo die Stellschrauben für eine erfolgreiche Intervention sind. Der Aufbau des Bildungsberichts orientiert sich grundsätzlich an den chronologischen Stufen einer idealtypischen Bildungsbiographie und an den durchlaufenen Einrichtungen, wobei eine Einbettung in einen gesamthaften sozialen Kontext erfolgt. Hieraus begründet sich die thematische Spannbreite der zusammengestellten Informationen. Da die Lebens- und Aufwachsbedingungen im Stadtgebiet erheblich differieren, erfolgt die Berichterstattung in vielen Segmenten in kleinräumiger Betrachtungsweise. (DIPF/Orig.)

Breast milk levels of zinc and omega-6 polyunsaturated fatty acids and growth of healthy Chinese infants

AIM: To examine the concentrations of zinc and omega-6 polyunsaturated fatty acids (omega-6 PUFAs) in breast milk, the impact of zinc on omega-6 PUFA metabolism, and the growth rate of infants. METHODS: Forty-one mother-term infant pairs from a rural area of northern Beijing, China, who were 1 month (n = 18, group I) and 3 months (n = 23, group II) old and exclusively breastfed, were studied. The dietary records and the concentrations of zinc and omega-6 PUFAs in the milk of lactating women and the increase in weight and length of their infants during 1 and 3 postnatal months were analysed. RESULTS: The dietary intakes of mothers in the two groups were the same, i.e. high in carbohydrate and low in fat, protein and energy. The maternal zinc intake was 7.5mg/d and thus reached only 34.6% of the current Recommended Nutrient Intake (RNI). The levels of zinc and arachidonic acid (AA, C20:4 omega-6) in the milk of group I were significantly higher than those in group II. Furthermore, significant positive correlations were found between the concentrations of zinc and AA in the breast milk and between the level of milk AA and weight gain. CONCLUSION: Zinc may be a co-factor and essential for essential fatty acids (EFA) metabolism. Thus suboptimal zinc intake may cause EFA imbalance. Further studies of Chinese rural mother-infant pairs are necessary to determine whether zinc supplementation should be recommended when lactation exceeds 3 months.

Bildung im Rems-Murr-Kreis. Zweiter Bildungsbericht 2014

Analog zum ersten Bildungsbericht ist der zweite Bildungsbericht in sechs Kapitel unterteilt, deren Reihenfolge sich - mit Ausnahme des ersten und letzten Kapitels - am Lebenslauf orientiert: (..) Kapitel A beschäftigt sich mit gesellschaftlichen und wirtschaftlichen Rahmenbedingungen von Bildung und geht in diesem Zusammenhang auf die Bevölkerungsentwicklung, die Arbeitsmarktsituation sowie die soziale Lage im Rems-Murr-Kreis ein. Anschließend wird in Kapitel B die frühkindliche Bildung in den Blick genommen. Der Fokus liegt hier auf der Betreuungssituation der Kinder unter sechs Jahren im Rems-Murr- Kreis, dem Thema Elternbildung sowie auf dem Übergang von der Kindertageseinrichtung in die Grundschule. Kapitel C widmet sich den allgemeinbildenden Schulen im Landkreis. Neben der Schüler- und Angebotsstruktur und dem Erwerb allgemeinbildender Schulabschlüsse wird auf aktuelle schulpolitische Entwicklungen und Maßnahmen zur Berufsorientierung eingegangen. Es folgt Kapitel D zur beruflichen Bildung im Rems- Murr-Kreis, in dem Schülerzahlen und Angebote der Beruflichen Schulen dargestellt werden. Außerdem werden die Themen berufsvorbereitende Bildungsgänge und duale Ausbildung behandelt. In Kapitel E wird die Bildungssituation der beruflichen Weiterbildung und der Erwachsenenbildung dargestellt. Abschließend befasst sich das Kapitel F mit non-formaler Bildung und informellem Lernen, wobei der Fokus auf den Jugendlichen im Rems-Murr-Kreis liegt. Es werden die non-formalen Bildungsorte Musik- und Kunstschulen, Bibliotheken und Einrichtungen der Jugendarbeit in den Blick genommen. Am Ende jedes Kapitels wird darüber hinaus erstmalig auf das Querschnittsthema Inklusion eingegangen. (DIPF/Orig.)

Erziehung und Bildung in Offenbach. Bericht 2015

Der Bericht "Erziehung und Bildung in Offenbach. Bericht 2015" (EBO), herausgegeben von Stadt Offenbach am Main, wird zum 9. Mal veröffentlicht. Erstmals wurden Daten der integrierten Ausbildungsberichterstattung für Hessen (iABE) einbezogen. Sie ermöglichen eine wohnortspezifische Analyse der Übergänge von der Sekundarstufe I in unterschiedliche Zielbereiche, wie z.B. Berufsabschluss oder Hochschulreife. Der EBO 2015 bietet vermehrt Zeitreihen, um langfristige Entwicklungen im Bildungsbereich darzustellen. Der Standortbestimmung dienen darüber hinaus interkommunale Vergleiche. Der EBO beinhaltet seit dem Bericht 2009 den von der Jugendhilfeplanung entwickelten „Index bildungsrelevanter sozialer Belastung“. Mit diesem können besondere pädagogischen Bedarfe in den 14 Grundschulbezirken ermittelt und faire, d.h. die unterschiedlichen Anteile bildungsbenachteiligter Schüler/-innen berücksichtigende, Schulleistungsvergleiche ermöglicht werden. Im Rahmen dieser Analyse rücken erstmals die Mädchen mit Migrationshintergrund in den Fokus: So fällt auf, dass im Übergang Grundschule/Gymnasium die Übergangsquote bei Mädchen mit Migrationshintergrund um 15 Prozentpunkte niedriger liegt als die der Mädchen ohne Migrationshintergrund. Sie liegt sogar knapp unter der Übergangsquote der Jungen mit Migrationshintergrund. Eine Erklärung dafür, dass die Mädchen mit Migrationshintergrund beim Übergang zum Gymnasium nicht zu den Bildungsgewinnern zählen, steht aber aus. Der Bericht verdeutlicht auch, dass der Bereich der Sprachförderung in allen Bildungsbereichen – „lebenslang“ – in der Kommune eine herausragende Rolle spielt. Der Bericht greift Linien des "Orientierungsrahmen für Bildungsentwicklung“ der Stadt Offenbach" auf. Der Prozess und die Erarbeitung wurden erstmals von der Fachstelle Bildungskoordinierung und Beratung federführend koordiniert. (DIPF/Autor)

Qualitative methods in the study of children's racial attitudes and identities

This article examines the role that qualitative methods can play in the study of children's racial attitudes and behaviour. It does this by discussing a number of examples taken from a qualitative, ethnographic study of five- and six-year-old children in an English multi-ethnic, inner-city primary school. The examples are used to highlight the limitations of research that relies solely on quantitative methods and the potential that qualitative methods have for addressing these limitations. Within this context the article contrasts the strengths and weaknesses of qualitative and quantitative methods in the study of children's racial attitudes and identities. The article concludes by arguing that a much more integrated multi-method approach is needed in this area and sets out some of the most effective ways this could be achieved.

Development of Illusory contour perception in infants

We investigated whether infants from 8 ^ 22 weeks of age were sensitive to the illusory contour created by aligned line terminators. Previous reports of illusory-contour detection in infants under 4 months old could be due to infants' preference for the presence of terminators rather than their configuration. We generated preferential-looking stimuli containing sinusoidal lines whose oscillating, abutting terminators give a strong illusory contour in adult perception. Our experiments demonstrated a preference in infants 8 weeks old and above for an oscillating illusory contour compared with a stimulus containing equal terminator density and movement. Control experiments excluded local line density, or attention to alignment in general, as the basis for this result. In the youngest age group (8 ^ 10 weeks) stimulus velocity appears to be critical in determining the visibility of illusory contours, which is consistent with other data on motion processing at this age. We conclude that, by 2 months of age, the infant's visual system contains the nonlinear mechanisms necessary to extract an illusory contour from aligned terminators.