Induction and measurement of IgE : a study in mice, with emphasis on the regulatory role of lymphokines

A better understanding of the regulatory mechanisms and cellular interactions of the IgE antibody response is of fundamental interest to allergologists and clinical immunologists because of the role of IgE in the pathogenesis of the immediate type allergic disease. In addition, basic knowledge of the regulation of IgE antibody formation may lead to new forms of treatment including suppression of excessively formed IgE antibody. Beyond the clinical significance, the IgE antibody response provides an excellent model to establish the interdependencies and regulatory events governing the expression of different isotypes at different levels. The formation of IgE antibodies is regulated by T cells and controlled by antigen- and/or isotype-specific interactions. Thus, external modulation of IgE production can be achieved by antigen, idiotype and anti-idiotype, being specific recognition elements in the establishment and control of an immune response. Also IgE specific regulatory factors and receptors on different types of cells exert a regulatory influence. In the case of isotype-specific regulation, total IgE antibody may be affected irrespective of its specificity. This is of relevance for eventual treatment of generalized IgE mediated allergic diseases. On the other hand, an antigen-specific modulation of an immune response will also affect the expression of other isotypes, even in a secondary response. From the above it is clear that much of the knowledge on the induction of the allergic inflammation gained from animal studies is clinically relevant. Moreover, the basic mechanisms of IgE regulation seem to be similar in man and in mice and rats. This is the underlying premise for these studies. The purpose of the investigations presented in this thesis was to get more insight into the mechanisms underlying the induction of IgE antibody formation in the mouse and the regulation of this IgE synthesis. For this study the development of suitable reagents and appropriate assay systems was indicated. Only since the availability of antigen-specific mouse IgE-secreting hybridomas, it became feasible to isolate enough IgE for the induction of heterologous anti-IgE antisera. This purified IgE can also be used as a reference standard in the quantitative determination of IgE. Furthermore, the hybridoma cells can be employed for the standardization of techniques that allow the determination of IgE-secreting cells. It is therefore that in Chapter 4 we focuss on the isolation and purification of monoclonal murine IgE, the generation of heterologous IgE-specific antisera and the development of a Terasaki-ELISA system for the quantitative determination of secreted IgE. Employing one of these an

Enhanced catch-up growth after a challenge in animals on organic feed

A feeding experiment was performed in two generations of three groups of chickens with different immune responsiveness. All groups were fed identically composed feeds from either organic or conventional production. In the young animals of the second generation an immune challenge was imposed. The chickens fed conventional feed showed overall a higher weight gain, whereas feed intake of the groups was similar. The animals on organic feed showed an enhanced immune reactivity, a stronger reaction to the immune challenge, as well as an enhanced ’catch-up-growth’ after the challenge

Is ADHD een (niet-)allergische overgevoeligheid? Een hypothese

Onderzoeksresultaten naar het causale verband tussen ‘Attention-deficit hyperactivity disorder’ (ADHD) en allergieën zijn niet eenduidig. Allergieën zoals astma en eczeem zijn klinische syndromen waarbij zowel genetische aanleg als omgevingsfactoren (huisdieren, huisstofmijten, pollen en voeding) kunnen bijdragen tot de ontwikkeling ervan. De hypothese dat ADHD bij sommige kinderen ook een allergie kan zijn, wordt onderbouwd aan de hand van de verschillende mechanismen die ten grondslag liggen aan zowel ADHD als allergische aandoeningen. Volgens de geaccepteerde terminologie voor allergie voldoet ADHD aan de criteria van overgevoeligheid, allergie en atopie. Deze hypothese zal in gerandomiseerd gecontroleerd onderzoek getoetst moeten worden. Hierbij moet niet alleen gebruik gemaakt worden van immunologisch onderzoek, maar ook van genetisch onderzoek. Dit omdat genen die gerelateerd worden aan het immuunsysteem met ADHD geassocieerd kunnen worden. Immunotherapeutische benaderingen, zoals immunotherapie en probiotica, zouden betrokken kunnen worden bij de behandeling van ADHD. Wanneer overgevoeligheid voor omgevingsfactoren, zoals voedingsmiddelen, bijdraagt aan het manifest worden van ADHD, zal de diagnostiek en de behandeling van ADHD herzien moeten worden, om zo de kwaliteit van zorg voor deze patiënten te verbeteren

Cytokines as cellular communicators

Cytokines and their receptors are involved in the pathophysiology of many diseases. Here we present a detailed review on cytokines, receptors and signalling routes, and show that one important lesson from cytokine biology is the complex and diverse regulation of cytokine activity. The activity of cytokines is controlled at the level of transcription, translation, storage, processing, posttranslational modification, trapping, binding by soluble proteins, and receptor number and/or function. Translation of this diverse regulation in strategies aimed at the control of cytokine activity will result in the development of more specific and selective drugs to treat diseases

Citrus/Cydonia Comp. Can Restore the Immunological Balance in Seasonal Allergic Rhinitis-Related Immunological Parameters In Vitro

In two in vitro studies, we examined the immunological (pathways of the) effects of Citrus/Cydonia comp. from, respectively, a healthy and an allergic donor; peripheral blood mononuclear cells (PBMCs) were isolated out of peripheral blood and analyzed in vitro after polyclonal stimulation of T-cells. The differentiation capacity and the influence with regard to Th1 (IFN-γ) and Th2 (IL-5) cells were examined. Citrus/Cydonia comp. has a selective effect on the differentiation of T-cells by producing relatively more IL-10 than IL-12. By that, it also seems to have an effect on the induction of regulatory (IL-10 producing) T-cell subsets. It is in vitro capable of neutralizing (to some extent) the changes, characteristic to allergic rhinitis, with regard to the maturation, differentiation, and activity of the immune system. Thus, Citrus/Cydonia comp. can potentially restore the disturbed immune state of rhinitis patients, which essentially could be sufficient to make allergic symptoms disappear permanently

Nutrition and Allergic Diseases

The purpose of this Special Issue, “Nutrition and Allergic Diseases”, is to provide an overview of the role of nutrition in allergy. The prevalence of asthma, rhinitis, and food allergy has increased tremendously over the last few decades. Is there a role for nutrition to help managing this global challenge? This Special Issue touches upon the many aspects that relate to nutrition and allergy and focuses on two fundamental questions: 1) Can nutrition play a role in allergy prevention and induction? 2) Can nutrition play a role in managing allergies? The topics covered range from the epidemiology of nutrition and allergy prevalence to the description of food components known to have beneficial effects on allergy, and include the importance of pregnancy and breastfeeding, the possibility of therapeutically targeting the microbiota in allergic diseases (with pre- or probiotics), the allergic effects of food processing, food allergies and related available treatments

Bloodmeal digestion by strains of Anopheles stephensi Liston (Diptera: Culicidae) of differing susceptibility to Plasmodium falciparum

Blood digestion was studied in strains of Anopheles stephensi which had been genetically selected for either refractoriness or susceptibility to infection by Plasmodium falciparum. Females of the refractory Pb3—9a strain ingested more blood than selected (Sda-500) and unselected (Punjab) susceptible females and began to degrade the haemoglobin soon after feeding. In susceptible females, haemoglobin degradation started only after a significant post-feeding lag period. Total protein content of the midgut after the bloodmeal was correspondingly higher for refractory than for susceptible females, but absolute and relative rates of protein degradation were not significantly different between the different mosquito strains. Bloodmeal induction of midgut trypsin activity and the maximal trypsin activity were the same for the different strains. The residual aminopeptidase activity and its relative post-feeding activity (enzyme units per midgut) were significantly higher in refractory females. However, when converting to specific aminopeptidase activity, no differences between strains were evident. The results indicate that both the early initiation of haemoglobin degradation and higher aminopeptidase activity in the Pb3—9a refractory strain are important in the limitation of parasite development within the mosquito midgut, whereas trypsin plays no role in this proces