Objetivo The objectives of the present proposal are to study the relationship between dose, wavelength and duration of UVB exposure and the effect on resistance to infections. The proposed studies will further advance knowledge with respect to mechanisms controlling adaptation, immunological tolerance and susceptibility of humans and animals. This information is necessary to improve the risk estimation for effects of UVB on the resistances to infections. Using mathematical models describing relationships between different parameters of the immune system and resistance to infections, animal data will be extrapolated to the human situation. The project will also investigate whether available epidemiological data on relevant infections in man are suitable for validation of the mathematically calculated (extrapolated) data.* Immune system The target cells, i.e. keratinocytes, LCs, fibroblasts, T cells, mast cells, NK cells, PMNLs will be studied with respect to UV-effects in different species. The effects, i.e. altered release or production of mediators or altered expression of surface markers will be studied. Both in vivo and in vitro exposure experiments are necessary. Additionally, the role of urocanic acid (UCA) and DNA will be examined with respect to their roles as initiators of UVB-induced immunosuppression. * Infections 1. Skin-associated infections. Responsible triggers for recurrent herpes simplex (HSV) infections in man and animal will be further analyzed: both genotoxic and immunotoxic phenomena may play a role. Tools to analyse these triggers are in vivo and ex vivo/in vitro specific immune responses to the pathogen in animals and man. For special purposes, transgenic animal models will be used (i.e. cytokine deficient, DNA repair deficient, UCA deficient). Immune responses studied are functional activity of lymphocytes, keratinocytes, LCs. In vivo readout systems are pathogen detection, contact and delayed-type hypersensitivity, immunopathology, antibody production. Ex vivo/in vitro read out systems used are: cytokines, adhesion molecules, major histocompatibility complex antigens, lymphocyte proliferation, cytotoxic T cell activity. Skin-associated infections that will be investigated include HSV and varicella zoster virus (VZV). 2. Non-skin-associated infections. By relating climatology data (sunshine, UVB exposure, etc.) from the last 20 years with data dealing with the incidence of infectious diseases in humans, it may be possible to analyze the effect of UVB exposure on the incidence and severity of infectious diseases. Non-skin-associated infections that will be investigated in animals include those caused by cytomegalovirus, murine gammaherpes virus (similar to human UVB), Trichinella spiralis, influenza, and Listeria monocytogenes. * Genotoxicity In man and mice expression of p53, as well as the frequency of p53 mutations, will be studied and related to UVB induced immunosuppression. Two transgenic mouse strains that are deficient either with respect to DNA repair or to p53 dependent apoptosis, will be used as tools to investigate whether DNA damage is important for the effects on the resistance to infections. * Risk-analysis Animal models and reserach in humans will be performed to select biomarkers that can be used to comprehend mechansms controlling adaptation, tolerance and sysceptibility, which are necessary for a solid risk assessment. All the data obtained by the different participants will be further described in quantitative terms in a mathematical model, and be integrated for a better risk-estimation. Epidemiology will be applied for validation of the analysis. Ámbito científico natural sciencesbiological sciencesgeneticsDNAmedical and health scienceshealth sciencespublic healthepidemiologymedical and health scienceshealth sciencesinfectious diseasesRNA virusesinfluenzamedical and health sciencesbasic medicineimmunologymedical and health scienceshealth sciencesinfectious diseasesDNA viruses Programa(s) FP4-ENV 2C - Specific programme of research and technological development in the field of environment and climate, 1994-1998 Tema(s) 01020202 - Alteration of processes as a result of UV-B radiation Convocatoria de propuestas Data not available Régimen de financiación CSC - Cost-sharing contracts Coordinador Rijksinstituut voor Volksgezondheid en Milieuhygiëne Aportación de la UE Sin datos Dirección 9,Antonie van Leeuwenhoeklaan 3720 BA Bilthoven Países Bajos Ver en el mapa Coste total Sin datos Participantes (5) Ordenar alfabéticamente Ordenar por aportación de la UE Ampliar todo Contraer todo Rijksuniversiteit Utrecht Países Bajos Aportación de la UE Sin datos Dirección 100,Heidelberglaan 3508 GA Utrecht Ver en el mapa Coste total Sin datos UNIVERSITY OF EDINBURGH Reino Unido Aportación de la UE Sin datos Dirección Teviot Place EH8 9AG EDINBURGH Ver en el mapa Coste total Sin datos UNIVERSITY OF TURKU Finlandia Aportación de la UE Sin datos Dirección 4-8,Kiinamyllynkatu 4-8 20520 TURKU / ABO Ver en el mapa Coste total Sin datos University of Dundee Reino Unido Aportación de la UE Sin datos Dirección Ninewells Hospital and Medical School DD1 9SY Dundee Ver en el mapa Coste total Sin datos Università Cattolica del Sacro Cuore Italia Aportación de la UE Sin datos Dirección Largo Agostino Gemelli 8 00168 Roma Ver en el mapa Coste total Sin datos