Humoral immune responses induced by Kudoa sp. (Myxosporea: Multivalvulida) antigens in BALB/c mice

The majority of Kudoa species infect the somatic muscle of fish establishing cysts. As there is no effective method to detect infected fish without destroying them these parasited fish reach the consumer. This work was developed to determine whether this parasite contains antigenic compounds capable of provoking an immune response in laboratory animals, in order to consider the possible immunopathological effects in man by the ingestion of Kudoa infected fish. BALB/c mice were injected by the subcutaneous route with the following extracts suspended in aluminium hydroxide: group 1 (black Kudoa sp. pseudocyst extract), group 2 (white Kudoa sp. pseudocyst extract), and group 3 (non-infected hake meat extract). Specific antibody levels were measured by ELISA against homologous and heterologous antigens. The highest responses were obtained from the black Kudoa sp. pseudocyst extract (group 1).The low optic density levels detected in group 3 proved that the results obtained in groups 1 and 2 were a consequence of the parasitic extract injection. The IgG1 was the predominant subclass. IgE detected in groups 1 and 2 showed the possible allergenic nature of some of the components of the parasitic extract. High IgA levels and medium IgG2a and IgG3 levels were obtained in groups 1 and 2. Low IgG2b responses were shown. No cross-reactions between Kudoa sp. pseudocyst extracts and the non-infected hake meat extract were observed.

Effects of corticosterone on innate and humoral immune functions and oxidative stress in barn owl nestlings.

The costs of coping with stressful situations are traded-off against other functions such as immune responses. This trade-off may explain why corticosterone secretion reduces immune reactions. Corticosterone differentially affects various immunity components. However, which component is suppressed varies between studies. It remains unclear whether the trade-off in energy, nutrition, autoimmunity or oxidative stress accounts for differential immunosuppression. In this study, we investigated whether corticosterone differentially affects the constitutive innate and humoral acquired immunity. We used barn owl nestlings, implanting 50% with a corticosterone-releasing pellet and the other 50% with a placebo pellet. To measure the effect on humoral immunity we vaccinated 50% of the corticosterone-nestlings and 50% of the placebo-nestlings with the antigens 'Tetravac' and the other 50% were injected with PBS. To assess the costs of elevated corticosterone, we measured body mass and resistance to oxidative stress. Administration of corticosterone increased corticosterone levels whereas vaccination induced the production of antibodies. Corticosterone reduced the production of antibodies, but it did not significantly affect the constitutive innate immunity. Corticosterone reduced body growth and resistance to oxidative stress. Under stressful conditions barn owl nestlings seem to keep the constitutive innate immunity, whereas elevated corticosterone levels negatively affected inducible immune responses. We found evidence that mounting a humoral immune reaction is not costly in terms of growth, but reduces the resistance to oxidative stress independently of corticosterone administration. We suggest that humoral immunity is suppressed because the risk of immunopathologies may be disproportionately high when mounting an antibody response under stressful situations.

Disease-driven T cell activation predicts immune responses to vaccination against melanoma.

Tumor vaccines may induce activation and expansion of specific CD8 T cells which can subsequently destroy tumor cells in cancer patients. This phenomenon can be observed in approximately 5-20% of vaccinated melanoma patients. We searched for factors associated with T cell responsiveness to peptide vaccines. Peptide antigen-specific T cells were quantified and characterized ex vivo before and after vaccination. T cell responses occurred primarily in patients with T cells that were already pre-activated before vaccination. Thus, peptide vaccines can efficiently boost CD8 T cells that are pre-activated by endogenous tumor antigen. Our results identify a new state of T cell responsiveness and help to explain and predict tumor vaccine efficacy.

The Healthy Weight Challenge

To help encourage, facilitate and empower people to adopt healthy lifestyles and to raise awareness of obesity and its causes in order to reduce its prevalence within the target community. Outcome Through Health Classes, Leaflets and Posters, people have developed their knowledge and understanding of obesity. The relationship between members of the community and the pharmacist has also developed as as has the Pharmacists links with GPs, Dieticians, Leisure Centre Management etcï_… All participants thought the healthy weight challenge was a good idea, made them more aware of health and the pharmacy was able to offer advice, information, support and health checks. regular monitoring also helped have a positive impact on participants desire to lose weight and also had positive impact on their efforts to have healthier lifestyle.

Highly diverse TCRα chain repertoire of pre-immune CD8(+) T cells reveals new insights in gene recombination.

Although the T-cell receptor αδ (TCRαδ) locus harbours large libraries of variable (TRAV) and junctional (TRAJ) gene segments, according to previous studies the TCRα chain repertoire is of limited diversity due to restrictions imposed by sequential coordinate TRAV-TRAJ recombinations. By sequencing tens of millions of TCRα chain transcripts from naive mouse CD8(+) T cells, we observed a hugely diverse repertoire, comprising nearly all possible TRAV-TRAJ combinations. Our findings are not compatible with sequential coordinate gene recombination, but rather with a model in which contraction and DNA looping in the TCRαδ locus provide equal access to TRAV and TRAJ gene segments, similarly to that demonstrated for IgH gene recombination. Generation of the observed highly diverse TCRα chain repertoire necessitates deletion of failed attempts by thymic-positive selection and is essential for the formation of highly diverse TCRαβ repertoires, capable of providing good protective immunity.

Cellular immune responses and disease control in acute AIDS-associated Kaposi's sarcoma.

Kaposi's sarcoma-associated herpesvirus (KSHV) specific T cell responses and KSHV viremia were analyzed in seven HIV-infected patients with active Kaposi's sarcoma lesions who initiated highly active antiretroviral therapy, and were compared between patients with improved Kaposi's sarcoma and those with progressive Kaposi's sarcoma requiring further systemic chemotherapy. Patients with controlled Kaposi's sarcoma disease demonstrated undetectable Kaposi's sarcoma viremia together with KSHV-specific CD8 T cells secreting interferon-gamma and tumor necrosis factor-alpha, whereas progressors showed increasing viremia with weak or no T-cell responses. These data point toward a potential role of KSHV-specific immunity in the control of AIDS-associated Kaposi's sarcoma.

Whole blood assay to access T cell-immune responses to Mycobacterium tuberculosis antigens in healthy Brazilian individuals

The production of interferon gamma (IFNgamma) guarantees effective T cell-mediated immunity against Mycobacterium tuberculosis infection. In the present study, we simply compare the in vitro immune responses to Mycobacterium antigens in terms of IFNg production in a total of 10 healthy Brazilian volunteers. Whole blood and mononuclear cells were cultivated in parallel with PPD, Ag85B, and M. bovis hsp65, and five-days supernatants were harvested for cytokine detection by ELISA. The inter-assay result was that the overall profile of agreement in response to antigens was highly correlated (r² = 0.9266; p = 0.0102). Potential analysis is in current progress to dictate the usefulness of this method to access the immune responses also in tuberculosis patients and its contacts.

Immune monitoring design within the developmental pipeline for an immunotherapeutic or preventive vaccine

Immunotherapy is defined as the treatment of disease by inducing, enhancing, or suppressing an immune response, whereas preventive vaccination is intended to prevent the development of diseases in healthy subjects. Most successful prophylactic vaccines rely on the induction of high titers of neutralizing antibodies. It is generally thought that therapeutic vaccination requires induction of robust T-cell mediated immunity. The diverse array of potential or already in use immunotherapeutic and preventive agents all share the commonality of stimulating the immune system. Hence, measuring those vaccination-induced immune responses gives the earliest indication of vaccine take and its immune modulating effects.

Obesity - an acknowledged public health challenge

As we face a difficult economic climate, in which inequalities may worsen, the PHA faces many challenges in its efforts to improve the health of the population. One such challenge is the issue of obesity. Recently, in the Draft Programme for Government and, again today, in anticipation of the publication of the Consultation on the Review of Health and Social Care Services in Northern Ireland, the specific issue of obesity has been highlighted in the media.The PHA is committed to playing a lead role in tackling this major health issue and has been systematically examining the evidence of best practice and effectiveness to ensure that investment and working in partnership will bring clear benefits. A welcome consequence of any success would be a reduction in the impact of the physical, and emotional costs of obesity related ill-health to individuals - and the financial costs to an overstretched healthcare system.A multi-facetted approach to tackling obesity is required for Northern Ireland. This will mean working across government departments, looking at relevant legislation, taxation, food standards and labelling, as well as supporting a raft of programmes within education, workplace, and at the local community level."The prevalence of overweight and obesity has risen dramatically in recent years in Northern Ireland and is now the norm to be overweight, rather than the exception. The Northern Ireland Health and Social Wellbeing Survey (2010-11) indicated that 36% of adults are overweight and a further 23% are obese; this means that approximately 3 in 5 adults in Northern Ireland carry excess weight. A similar proportion of males and females were obese (23%) however males were more likely to be overweight (44%) than females (30%).Data from the Northern Ireland Health and Wellbeing Survey (2010-11) reported that 27% of children aged 2-15 years are obese or overweight. The findings presented here are based on the guidelines put forward by the International Obesity Task Force. Using this approach, 8% of children were assessed as obese, with similar results for boys (8%) and girls (9%). Obesity has serious implications for health and wellbeing and is associated with an increased risk of heart disease and stroke, type 2 diabetes, some cancers, respiratory problems and joint pain.Evidence indicates that being obese can reduce life expectancy by up to 9 years; and it can impact on emotional and psychological well-being and self-esteem, especially among young people.Obesity also impacts on wider society through economic costs, loss of productivity and increased demands on our health and social care system. It is estimated that obesity in Northern Ireland is resulting in 260,000 working days lost each year with a cost to the local economy of £500 million.The good news is that the intentional loss of significant weight (approx 10kg) in overweight and obese adults has been shown to confer significant health benefits, decreased morbidity and may also reduce obesity-related mortality.Key programmes and interventions are undertaken by the PHA in order to prevent and reduce overweight and obesity. The programmes/interventions are supported by significant ongoing work at local level. Examples include:the promotion of breastfeeding; local programmes to increase awareness of good nutrition and develop cooking skills, for example 'Cook It!'; promotion of more active lifestyles, for example, Walking for Health' and 'Teenage Kicks'; development of community allotment schemes; programmes for primary school children, for example Skip2bfit and Eat, Taste and Grow; and sports and other recreation, for example 'Active Belfast'. The PHA's multi media campaign 'It all adds up!' to encourage children to become more active and understand the importance of keeping fit, in a fun and exciting way, ran until October 2011. It encouraged parents and carers to go to the website www.getalifegetactive.com and download the PHA logbook It all adds up! to plan activities as a family. The logbook helped children and parents plan and keep track of their participation in physical activity at school, home and in the community. PHA is currently developing a public information campaign and other supportive work to increase public awareness of obesity as well as to provide advice and support for those who want to make real changes. The campaign development is well underway and is anticipated for launch in late Spring 2012. Like many common health problems, people living in disadvantaged circumstances suffer most and the PHA is committed to tackling this aspect of health inequality. The good news is that even a modest weight loss, of 1-1 Â_ stones, can help to reduce the risk of many of the health problems resulting from being overweight or obese. Information on losing weight through healthier eating and being more active can be found on the PHA websites - www.enjoyhealthyeating.info and www.getalifegetactive.com . These websites provide help and advice for anyone who wants to improve their eating habits and fitness levels, by making small, sustainable, healthy changes to their lifestyle. The PHA leaflet, Small changes, big benefits is also available to download from the PHA website, 'Publications' section.

Multiple imputations applied to the DREAM3 phosphoproteomics challenge: a winning strategy.

DREAM is an initiative that allows researchers to assess how well their methods or approaches can describe and predict networks of interacting molecules [1]. Each year, recently acquired datasets are released to predictors ahead of publication. Researchers typically have about three months to predict the masked data or network of interactions, using any predictive method. Predictions are assessed prior to an annual conference where the best predictions are unveiled and discussed. Here we present the strategy we used to make a winning prediction for the DREAM3 phosphoproteomics challenge. We used Amelia II, a multiple imputation software method developed by Gary King, James Honaker and Matthew Blackwell[2] in the context of social sciences to predict the 476 out of 4624 measurements that had been masked for the challenge. To chose the best possible multiple imputation parameters to apply for the challenge, we evaluated how transforming the data and varying the imputation parameters affected the ability to predict additionally masked data. We discuss the accuracy of our findings and show that multiple imputations applied to this dataset is a powerful method to accurately estimate the missing data. We postulate that multiple imputations methods might become an integral part of experimental design as a mean to achieve cost savings in experimental design or to increase the quantity of samples that could be handled for a given cost.

Kid's food challenge

As parents and guardians many of you are making huge efforts to ensure your kids are eating healthily and limiting the number of sweets and unhealthy snacks they eat. You’ll know already that some of these treat foods are okay as part of a healthy balanced diet, but eating too many is not a good idea. At the moment, kids are eating on average about twice as many treat foods as they should be, so it’s time to think about cutting down.

Sugar Reduction: Responding to the Challenge

In ‘Sugar Reduction: Responding to the Challenge’, PHE is calling on charities, non-governmental organisations (NGOs), academics, businesses, retailers and consumers to work together to reduce the amount of sugar we eat as a nation. By analysing dietary data and discussing food habits with stakeholders, we have identified a range of areas that need exploring further. PHE already runs successful marketing campaigns designed to promote healthy living. To build on this, we also want to look at the way foods are being advertised to children, financial measures that relate to sugar sweetened drinks, food procurement across the public sector and education and training. Today, PHE received a draft report from the Scientific Advisory Committee on Nutrition (SACN): ‘Carbohydrates and Health’. PHE is particularly interested in SACN’s research because it is clear that the nation is consuming more sugar than the UK’s current recommendations. Diets high in sugar can contribute to excess calorie intake, which can lead to weight gain and obesity.