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

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

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

Cytokines in Clinical and Experimental Transplantation

Allograft rejection is a complex process, which requires interactions between different cell types and a variety of soluble factors, such as cytokines. In this review we discuss the role of cytokines in the induction and effector phases of the rejection process and in the induction and maintenance of allospecific graft tolerance. Furthermore, we discuss the feasibility of clinical graft function monitoring by measuring cytokines and the possibilities for intervention in the cytokine network in order to inhibit graft rejection and eventually obtain graft acceptance

Semi-preparative purification and validation of monoclonal antibodies for immunotherapy in mice

A number of rat hybridomas were adapted to grow in RPMI containing either 5% IgG-depleted FCS of 1% serum-free Nutridoma. Alternatively, protein-free Ultradoma PF was used. Growth in these media allowed purification procedures to be used that are based on tangential ultrafiltration in combination with affinity chromatography on gels linked to protein G or anti-rat L chain coupled antibodies. The isolated antibody preparations were found to be pure and to consist of monomeric intact IgG. The yield and recovery of mAb using this procedure were found to be consistently high. These antibody preparations were analyzed for endotoxin contamination. Whereas during isolation endotoxin contamination increased, the endotoxin content per mg purified protein did not. Affinity chromatography on Detoxi-gel resulted in the efficient removal of this contamination and using this protocol the antibody preparations obtained were found to be of sufficient purity, activity and low endotoxin content to permit their in vivo use in animal models of immunotherapy

Multidose Streptozotocin Induction of Diabetes in BALB/c Mice Induces a Dominant Oxidative Macrophage and a Conversion of T(H)1 to T(H)2 Phenotypes During Disease Progression

Macrophages (Mp) are implicated in both early and late phases in type 1 diabetes development. Recent study has suggested that a balance between reductive Mp (RMp) and oxidative Mp (OMp) is possible to regulate T(H)1/T(H)2 balance. The aim of this study is to investigate the redox status of peritoneal Mp and its cytokine profile during the development of autoimmune diabetes induced by multiple low-dose streptozotocin in BALB/c mice. Meanwhile, the polarization of T(H)1/T(H)2 of splenocytes or thymocytes was also examined. We found that peritoneal Mp appeared as an “incomplete” OMp phenotype with decreased icGSH along with disease progression. The OMp showed reduced TNF-α, IL-12, and NO production as well as defective phagocytosis activity compared to nondiabetic controls; however, there was no significant difference with IL-6 production. On the other hand, the levels of IFN-γ or IL-4 of splenocytes in diabetic mice were significantly higher compared to the control mice. The ratio of IFN-γ to IL-4 was also higher at the early stage of diabetes and then declined several weeks later after the occurrence of diabetes, suggesting a pathogenetic T(H)1 phenotype from the beginning gradually to a tendency of T(H)2 during the development of diabetes. Our results implied that likely OMp may be relevant in the development of type 1 diabetes; however, it is not likely the only factor regulating the T(H)1(H)/T(H)2 balance in MLD-STZ-induced diabetic mice

Vitamin D and Autism Spectrum Disorder

1,25(OH)2D is the hormonally active form of vitamin D known for its pleiotropic immunomodulatory effects. Via altering gene transcription, 1,25(OH)D exerts immunosuppressive effects and stimulates immune regulation. Recently, the interest in vitamin D in association with autism spectrum disorder (ASD) has been triggered. The prevalence of ASD has increased excessively over the last few decades, emphasizing the need for a better understanding of the etiology of the disorder as well as to find better treatments. Vitamin D levels in ASD patients are observed to be lower compared to healthy individuals and maternal vitamin D deficiency has been associated with an increased risk of ASD. Moreover, vitamin D supplementation improves ASD symptoms. These recent clinical findings strongly suggest that vitamin D is a factor in ASD onset and progression. Yet, possible mechanisms behind this association remain unknown. This review summarizes immunomodulatory properties of vitamin D and peripheral immune dysregulation in ASD, after which possible mechanisms via which vitamin D could rebalance the immune system in ASD are discussed. Although promising clinical results have been found, further research is necessary to draw conclusions about the effect and mechanisms behind the effect of vitamin D on ASD development