Exjobbsförslag från företag

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Förslaget inkom 2005-01-18

New tools for allergen-specific immunotherapy: mechanisms for regulation of the allergic immune response

Allergy is a common cause of chronic illness in our society and the need for curative treatments is evident. Today, specific immunotherapy (SIT) is the only curative treatment for allergic disease in use. This therapy is however time-consuming, expensive and not without risks for adverse side effects. To overcome the limitations of current SIT, this project aims to develop new strategies to improve the therapy. For this purpose, it is essential to understand the mechanisms for how an allergen, i.e. a substance causing allergy, induces an allergic immune response and how this response may be modified and skewed towards a ¿non-allergic¿ response. By changing the molecular nature and delivery conditions of an allergen, we hypothesize that we can influence on how an allergen is recognised by the immune system. This will in turn influence the T-cell response evoked and thus if the result will be an allergic response or not. A current hypothesis is that allergic patients have a defect regulatory T-cell response to allergens. The antigen-presenting cell (APC) taking up and presenting the allergen to the T-cell plays a key role in determining if the T-cell response will be a regulatory, healthy, immune response or if effector mechanisms will be activated.
At the department of Medicine, Clin. Immunology and Allergy unit, KI, we study regulatory mechanisms controlling the immune response to allergens. The aim is to learn how to activate the regulatory mechanisms, which normally control and suppress the allergic immune response towards allergens. In one project we will investigate two important cell types that control the immune response: dendritic cells (DC), wich is the most potent APC, and regulatory T-cells (Treg). For this purpose, blood cells from allergic patients and healthy controls will be collected after allergen exposure or without allergen exposure. The specific mechanisms for how DCs and Tregs control the immune response to allergens will then be investigated. In a second project we will evaluate a novel allergen carrier and adjuvant for allergen-specific immunotherapy (SIT), carbohydrate-based particles (CBP). A major cat allergen coupled to CBPs will be assessed in a human system for their effect on DCs and T-cell responses. Finally, at the present we are establishing a mouse model for cat allergy where we can test the therapeutic potency of allergen-coupled CBPs. This allergy model will also be used to test other new approaches to manipulate an allergic immune response in SIT.
Many methods will be employed in the projects described above. Cell fractioning and culture, cell analyses by flow cytometry, cell proliferation assays, cytokine production (e.g. ELISA, CBA, ELSISpot and QT-PCR), recombinant protein production and analyses are some examples of methods that are currently used in our laboratory.
Allergy to common inhalant allergens is an increasing problem in our society and almost one third of the population is affected. Therefore we need curative therapies to treat allergic diseases. The overall aim of this project is to learn how we can target allergens to be presented to the immune system in a ¿non-allergic¿ fashion in order to generate new tools for immunotherapy of allergic disease.


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