Oral Immune Defense against Chronic Hyperplastic Candidosis

Candida yeast species are widespread opportunistic microbes, which are usually innocent opportunists unless the systemic or local defense system of the host becomes compromised. When they adhere on a fertile substrate such as moist and warm, protein-rich human mucosal membrane or biomaterial surface, they become activated and start to grow pseudo and real hyphae. Their growth is intricately guided by their ability to detect surface defects (providing secure hiding , thigmotropism) and nutrients (source of energy, chemotropism). The hypothesis of this work was that body mobilizes both non-specific and specific host defense against invading candidal cells and that these interactions involve resident epithelial cells, rapidly responding non-specific protector neutrophils and mast cells as well as the antigen presenting and responding den-dritic cell lymphocyte plasma cell system. It is supposed that Candida albicans, as a result of dar-winistic pressure, has developed or is utilizing strategies to evade these host defense reactions by e.g. adhering to biomaterial surfaces and biofilms. The aim of the study was to assess the host defense by taking such key molecules of the anti-candidal defense into focus, which are also more or less characteristic for the main cellular players in candida-host cell interactions. As a model for candidal-host interaction, sections of chronic hyperplastic candidosis were used and compared with sections of non-infected leukoplakia and healthy tissue. In this thesis work, neutrophil-derived anti-candidal α-defensin was found in the epithelium, not only diffusely all over in the epithelium, but as a strong α-defensin-rich superficial front probably able to slow down or prevent penetration of candida into the epithelium. Neutrophil represents the main host defence cell in the epithelium, to which it can rapidly transmigrate from the circulation and where it forms organized multicellular units known as microabscesses (study I). Neutrophil chemotactic inter-leukin-8 (IL-8) and its receptor (IL-8R) were studied and were surprisingly also found in the candidal cells, probably helping the candida to keep away from IL-8- and neutrophil-rich danger zones (study IV). Both leukocytes and resident epithelial cells contained TLR2, TLR4 and TLR6 receptors able to recognize candidal structures via utilization of receptors similar to the Toll of the banana fly. It seems that candida can avoid host defence via stimulation of the candida permissive TLR2 instead of the can-dida injurious TLR4 (study V). TLR also provides the danger signal to the immune system without which it will not be activated to specifically respond against candidal antigens. Indeed, diseased sites contained receptor activator of nuclear factor kappa B ligand (RANKL; II study), which is important for the antigen capturing, processing and presenting dendritic cells and for the T lymphocyte activation (study III). Chronic hyperplastic candidosis provides a disease model that is very useful to study local and sys-temic host factors, which under normal circumstances restrain C. albicans to a harmless commensal state, but failure of which in e.g. HIV infection, cancer and aging may lead to chronic infection.

Merestä Metsäksi - yhteistoimintaverkostohankkeen sosiaaliset ja taloudelliset vaikutukset

The object of this study was to find out which factors made landowners interested in From Sea to Forest co-operation network. Co-operation networks protect biodiversity across boundaries and among groups of landowners with different kind of protection contracts. The social effects of From Sea to Forest - project are studied by analyzing the experience of co-operation and trust. Furthermore the possibility to influence decision making when choosing the pilot areas and doing the contracts was surveyed. Economical effects are estimated for those landowners, who signed a protection contract for ten years. The study is part of The Finnish Forest Research Institute s Ecological considerations in landscape-level collaborative planning of private forestry project. The material of the study comprises 13 interviews done in January 2006; seven interviewed were landowners and six forest professionals. The interviews were transcripted and analyzed with Atlas.ti programme. The economical effects were estimated with MOTTI forest simulation programme. From Sea to Forest project interested the landowners for similar reasons: the voluntariness of participation, compensation, fixed-term contracts and the possibility to protect forests so that the proprietary right remains. It was possible to form four different groups of interviewed landowners according to trust: networkers , opportunists , carefuls and selfemployed . Only in the group of opportunists the project created so much trust that a significant increase of interest to participate in the project was noticed. In all the other groups the project didn t create remarkable trust, so trust didn t have an effect on landowners decisions to participate. Other factors, like compensation and voluntariness were decisive for their interest to participate. From Sea to Forest project wasn t a network based on landowners co-operation, the communication was directly with the project worker. The effects on landowners income by signing a ten year ´Natural value trading´ -contract was analyzed by comparing the protection income with predicted forestry income in case that the protection contract wouldn t have been agreed on. For two landowners there was no suggested forestry work within ten years, so their protection income might be an additional income, if they decided to log their forests later. For three landowners delayed thinning of the sapling stand would cause income losses in the future, if they decided to move to active forestry after ten years of protection. For eight landowners the effect of protection is positive to income if they moved to active forestry after the ten years protection period. This occurred, because the tree stand is now mature for final felling on behalf of its age, but ten more years of growth increase the net present value. Longer term protection might diminish the net present value. The protection was profitable because hectare specific forestry income grew compared to forestry cutting plan income.