Human circulating T follicular helper cells during viral infection and autoimmunity

CD4+ T helper cells orchestrate the adaptive immune response. The differentiation of naïve CD4+ T cells into various functionally different subsets of T helper cells ensures the adaptation of the immune response to the invading pathogen. The T helper cell subset that is responsible for B cell help during affinity maturation in the germinal center (GC) reaction is called T follicular helper (Tfh) cells. Therefore, Tfh cells are crucial to develop long-lasting immunity by ensuring the generation of memory B cells and high-affinity antibody-producing plasma cells. Blood-resident Tfh cells, so called circulating Tfh (cTfh) cells, can be used to investigate human Tfh cells instead of lymphoid tissue-resident Tfh cells, which are difficult to assess in humans. Lymphoid tissue-resident Tfh cells and cTfh cells both provide B cell help and share similarities in phenotype and gene expression. cTfh cells can express other CD4+ T cell subset-defining chemokine receptors and can thereby be clustered into different subsets. Although increased cTfh cell frequencies have been connected to better vaccination outcome and new insights into cTfh cell kinetics might improve the understanding of established vaccinations and impact future vaccine design, only few studies investigated cTfh kinetics after vaccination. Most conclusions were drawn from annual influenza vaccinations that allow for investigation of recall responses. Nevertheless, it is difficult to distinguish between the primary and secondary immune response as vaccinees have likely been in contact with influenza virus before vaccination and additionally influenza vaccination can have low efficacy. Therefore, I tracked and characterized cTfh and other blood-resident immune cells by flow cytometry after challenge with a live virus in the context of a vaccination against yellow fever. Yellow fever virus (YFV) is endemic in tropical regions. Yellow fever vaccination elicits a strong, long-lasting immune response with neutralizing antibodies in almost all vaccinees. We were able to show that vaccination with the attenuated yellow fever virus elicited an increased frequency of activated cTfh cells from three days on after vaccination. The peak frequency of activated cTfh cells was detectable 14 days after vaccination. In addition, we observed a shift in the subset composition of cTfh cells during the immune response with cTfh1 cells as the most prevalent subpopulation. Those findings were confirmed by the detection of YFV-specific CD4+ T cells in the blood with major histocompatibility complex (MHC) II tetramers for four known epitopes. Moreover, we found a correlation of frequencies of cTfh1 cells with the strength of the neutralizing antibody response, which might influence future vaccine design. Tfh cells have also been implicated in the pathogenesis of several autoimmune diseases and are for example contained in ectopic lymphoid structures and implicated in the formation of autoantibodies. Multiple sclerosis (MS) often involves ectopic lymphoid structures and oligoclonal bands in the cerebrospinal fluid and multiple studies point to a role of Tfh cells in multiple sclerosis. Yet, cTfh cells and the impact of immunomodulatory drugs are not well investigated in patients with MS. Therefore, I compared blood-resident T and B cell populations of patients with multiple sclerosis, that either received no treatment or different immunomodulatory drugs, with cells derived from healthy donors. Although cTfh cells from MS patients were phenotypically not distinguishable from healthy donors, immunomodulatory treatment with the sphingosine-1-phosphate receptor (S1PR) 1 blocking drug fingolimod resulted in profoundly reduced frequencies of cTfh cells. Additionally, other T cells expressing the Tfh cell hallmark chemokine receptor CXCR5, such as T follicular regulatory cells and CXCR5+CD8+ T cells, were similarly affected. This provides insight into the migratory pattern of cTfh cells as well as a better understanding of the impact of fingolimod on blood-resident lymphocyte populations. In summary, the findings I present in this thesis contribute to a better understanding of circulating Tfh cells after viral challenge and immunomodulation. This might have implications for vaccine design and for the treatment of autoimmune diseases

More from the conversation with Mary Roach featured in TMR's Winter 2014 : "Paradise Lost" issue

Podcast"In our ... (Winter 2014 Issue) Josh Huber and Johanna Saleska spoke on the phone with writer Mary Roach. [In this] podcast, we have a selection from their wide-ranging interview, including some new content that didn't make it to the print interview.

Monitoring und Evaluation von Health Research Capacity Development auf individueller und organisatorischer Ebene

Drei der insgesamt „Acht Millenniums-Entwicklungsziele“ der Vereinten Nationen adressieren die Gesundheit des Menschen, z. B. die Bekämpfung von HIV/Aids und anderen Krankheiten. Für die erfolgreiche Umsetzung dieser Gesundheitsziele stellt die Durchführung adäquater Forschung eine fundamentale Voraussetzung dar. Es ist daher erforderlich, gesundheitsbezogene Forschungskompetenzen systematisch und zielorientiert aufzubauen, weiterzuentwickeln und zu verbreiten. Health Research Capacity Development (HRCD) kann hierzu einen wertvollen Beitrag leisten. Denn HRCD befähigt Individuen, Organisationen und Nationen dazu, wertvolle gesundheitsbezogene Forschung durchzuführen. Das Ziel dieser Arbeit war es, HRCD auf individueller und organisatorischer Ebene am Beispiel einer Forschungseinrichtung in Tansania zu evaluieren. Hierbei wurden zwei Forschungsfragen fokussiert betrachtet: 1) Die Vision der untersuchten Forschungseinrichtung und 2) der Abgleich der institutionellen Vision mit den forschungsbezogenen Kompetenzbedarfen der Mitarbeiterinnen und Mitarbeitern. Zur Beantwortung der beiden Forschungsfragen wurde eine klinische Forschergruppe am Mbeya Medical Research Center (MMRC) in Tansania an zwei Erhebungszeitpunkten qualitativ und quantitativ befragt. Die qualitativen Interviews behandelten u. a. die Themen „Selbsteinschätzung der Motivation und Forschungskompetenzen“, „Capacity Development am MMRC“ und „Karriereentwicklung“. Zur Messung der Forschungskompetenzen wurden neben den Fragen in den Interviews die quantitative „Research Spider“ von Smith et al. 2002 verwendet. Die Interviews wurden mit der strukturierenden Inhaltsanalyse nach Mayring 2010 ausgewertet und analysiert. Die Ergebnisse der Studie zeigen, dass die institutionelle Vision den Mitarbeiterinnen und Mitarbeitern nicht vollständig bekannt ist und sie die Ziele der Institution nur teilweise benennen können. Der Vergleich zwischen den qualitativ und quantitativ erhobenen Forschungskompetenzen wies eine hohe Deckungsgleichheit auf. Zugleich wurde deutlich, dass die Forscherinnen und Forscher bei einigen Forschungskompetenzen Defizite aufweisen, beispielsweise dem Publizieren von Artikeln in Fachzeitschriften, dem Management von Forschungsprojekten und der Leitung von Forschungsteams. In Zukunft sollte der Einfluss einer institutionellen Vision auf die individuelle Entwicklung von Forscherinnen und Forschern stärker beachtet und insbesondere Führungskompetenzen gefördert werden

Probióticos na prevenção e tratamento de doenças em Odontologia

Em meados do século XX mencionou-se que os búlgaros, que consumiam leite fermentado, viviam mais tempo e possuíam maior qualidade de vida em relação aos demais povos. Com o passar dos anos, pesquisas comprovaram que os microrganismos vivos contidos em probióticos são capazes de melhorar a saúde bucal, além de promover tantos outros benefícios em diferentes áreas do corpo humano. O objetivo com esta revisão de literatura foi relatar os benefícios dos probióticos em Odontologia, os mecanismos de ação dessas bactérias, as espécies que compõem esses nichos e quais as principais formas de administração. Os artigos científicos triados foram publicados entre 2005 e 2017 e originaram-se das bases de dados Scielo, PubMed e CAPES. O principal efeito benéfico observado em pacientes que consumiram probióticos foi o aumento das defesas do organismo. Além disso, em Odontologia, os probióticos têm exibido uma alta capacidade anti-inflamatória e são utilizados no tratamento de cáries, da candidíase oral e da halitose, apresentando, posteriormente, aplicações nas doenças periodontais. Os mecanismos de ação dessas bactérias, ao que tudo sugere, é que, além de promoverem modulação das defesas do hospedeiro, apresentam também capacidade de adesão às superfícies orais, tanto mucosas quanto superfícies duras, promovendo uma competição com as bactérias patogênicas. Os probióticos mais frequentes contêm Lactobacillus e Bifido­bacterium, contudo, outras cepas de bactérias foram isoladas, entre elas:  L. acidophilus, L. casei, L. rhamnosus, L. gasseri e L. reuteri. A forma comercial mais comum é a de bactérias inoculadas no leite e em seus derivados, como o iogurte, porém, podem ser encontradas sob a forma de sucos, balas, chicletes e embaladas como alimentos dietéticos. Conclui-se que a utilização de probióticos em Odontologia é de grande valia por auxiliar o profissional na prevenção e no tratamento de bactérias prejudiciais à saúde dos pacientes de forma saudável e natural.Palavras-chave: Probióticos. Patologias orais. Bactérias. Odontologia.

Monitoring und Evaluation von Health Research Capacity Development auf individueller und organisatorischer Ebene

Drei der insgesamt „Acht Millenniums-Entwicklungsziele“ der Vereinten Nationen adressieren die Gesundheit des Menschen, z. B. die Bekämpfung von HIV/Aids und anderen Krankheiten. Für die erfolgreiche Umsetzung dieser Gesundheitsziele stellt die Durchführung adäquater Forschung eine fundamentale Voraussetzung dar. Es ist daher erforderlich, gesundheitsbezogene Forschungskompetenzen systematisch und zielorientiert aufzubauen, weiterzuentwickeln und zu verbreiten. Health Research Capacity Development (HRCD) kann hierzu einen wertvollen Beitrag leisten. Denn HRCD befähigt Individuen, Organisationen und Nationen dazu, wertvolle gesundheitsbezogene Forschung durchzuführen. Das Ziel dieser Arbeit war es, HRCD auf individueller und organisatorischer Ebene am Beispiel einer Forschungseinrichtung in Tansania zu evaluieren. Hierbei wurden zwei Forschungsfragen fokussiert betrachtet: 1) Die Vision der untersuchten Forschungseinrichtung und 2) der Abgleich der institutionellen Vision mit den forschungsbezogenen Kompetenzbedarfen der Mitarbeiterinnen und Mitarbeitern. Zur Beantwortung der beiden Forschungsfragen wurde eine klinische Forschergruppe am Mbeya Medical Research Center (MMRC) in Tansania an zwei Erhebungszeitpunkten qualitativ und quantitativ befragt. Die qualitativen Interviews behandelten u. a. die Themen „Selbsteinschätzung der Motivation und Forschungskompetenzen“, „Capacity Development am MMRC“ und „Karriereentwicklung“. Zur Messung der Forschungskompetenzen wurden neben den Fragen in den Interviews die quantitative „Research Spider“ von Smith et al. 2002 verwendet. Die Interviews wurden mit der strukturierenden Inhaltsanalyse nach Mayring 2010 ausgewertet und analysiert. Die Ergebnisse der Studie zeigen, dass die institutionelle Vision den Mitarbeiterinnen und Mitarbeitern nicht vollständig bekannt ist und sie die Ziele der Institution nur teilweise benennen können. Der Vergleich zwischen den qualitativ und quantitativ erhobenen Forschungskompetenzen wies eine hohe Deckungsgleichheit auf. Zugleich wurde deutlich, dass die Forscherinnen und Forscher bei einigen Forschungskompetenzen Defizite aufweisen, beispielsweise dem Publizieren von Artikeln in Fachzeitschriften, dem Management von Forschungsprojekten und der Leitung von Forschungsteams. In Zukunft sollte der Einfluss einer institutionellen Vision auf die individuelle Entwicklung von Forscherinnen und Forschern stärker beachtet und insbesondere Führungskompetenzen gefördert werden

What are effects of a spaced activation of virtual patients in a pediatric course?

BACKGROUND: Virtual patients (VPs) have a long tradition in the curriculum of the medical faculty at the Ludwig-Maximilians-University (LMU) Munich. However, the pediatric VPs were not well integrated into the curriculum and hardly used by students. METHODS: Therefore we created and implemented a self-contained E-learning module based on virtual patients (VPs), which was embedded into the pediatric curriculum. Students taking this course were divided into two groups. For Group A the virtual patients were activated in a timed order (“spaced activation”), whereas Group B could work on all VPs from the beginning. We investigated the performance of these two groups concerning usage pattern including number of sessions and session duration, score on questions integrated into the VP and results of the intermediate exam. RESULTS: The integration of the VPs into the pediatric course was successful for both groups. The usage pattern for the spaced activation turned out to be more balanced, however we did not find any significant differences in the results of the intermediate exam, the score on questions included in the VPs nor in the time students spent working on the VPs. CONCLUSIONS: Our study showed that the spaced activation led to a more balanced VP usage pattern with a lower peak of sessions at the end of the course. Further studies will have to investigate whether a spaced activation of VPs leads to favorable long-term learning outcomes

Tools and instruments for needs assessment, monitoring and evaluation of health research capacity development activities at the individual and organizational level: a systematic review

Background: In the past decades, various frameworks, methods, indicators, and tools have been developed to assess the needs as well as to monitor and evaluate (needs assessment, monitoring and evaluation;"NaME") health research capacity development (HRCD) activities. This systematic review gives an overview on NaME activities at the individual and organizational level in the past 10 years with a specific focus on methods, tools and instruments. Insight from this review might support researchers and stakeholders in systemizing future efforts in the HRCD field. Methods: A systematic literature search was conducted in PubMed and Google Scholar. Additionally, the personal bibliographies of the authors were scanned. Two researchers independently reviewed the identified abstracts for inclusion according to previously defined eligibility criteria. The included articles were analysed with a focus on both different HRCD activities as well as NaME efforts. Results: Initially, the search revealed 700 records in PubMed, two additional records in Google Scholar, and 10 abstracts from the personal bibliographies of the authors. Finally, 42 studies were included and analysed in depth. Findings show that the NaME efforts in the field of HRCD are as complex and manifold as the concept of HRCD itself. NaME is predominately focused on outcome evaluation and mainly refers to the individual and team levels. Conclusion: A substantial need for a coherent and transparent taxonomy of HRCD activities to maximize the benefits of future studies in the field was identified. A coherent overview of the tools used to monitor and evaluate HRCD activities is provided to inform further research in the field