Objective * To establish the relationship between immune response to filarial parasite antigens and the length of exposure to transmission.* To identify major antigens from the infective L3 stage of Brugia malayi, as defined by reactivity with human immune sera and T cells.* To identify the major antigens from the microfilarial (Mf) stage, and to test for antigenic variants of these antigens.Expected Outcome* An understanding of stage-specific immune responses in pathology and immunity.* Molecular data on sequence and polymorphism of Mf sheath antigens.* Sequence and profile of immune recognition of L3 antigens.The immunology of exposure to and infection with lymphatic filarial parasites, with respect to T cell subsets and stage-specific antigens, will be assessed. The first aspect will be the relationship between exposure to filarial transmission and the evolution of immunomodulated responses, evident in a strongly TH2 biased, TH1 down-regulated profile. Patients subject to lifelong transmission of filariasis will be compared with immigrants into the same area whose exposure is limited to only 4 or 8 years. The progression of the T cell subset bias, and the development of antigen-specific unresponsiveness seen in filariasis, will be monitored. An important question is whether this subset bias relates primarily to the adult stage, or whether other stages are similarly involved.Secondly, prominent antigens from L3 and Mf stages will be isolated and cloned for functional analyses. The importance of such antigens in mediating protection against disease can be directly assessed using sera and T cells from the study populations; their biological role in the host-parasite relationship may also be deduced from database sequence similarities and the opportunity to discover new antigens from immature parasites through the new Filarial Genome Project.A number of other biological questions which underpin filarial disease and its cure will also be addressed. Preliminary evidence for antigenic polymorphism in the Mf sheath antigens will be pursued, using different isolates and species of filarial parasite. The interaction between the anti-filarial drug, DEC, and Mf antigens will be studied. The role of non-CD4 T cells, which may prejudice the immune response towards the TH2 pathway from a very early stage, will be examined. Fields of science medical and health sciencesbasic medicineimmunologymedical and health sciencesbasic medicinepathologynatural sciencesmathematicspure mathematicsmathematical analysisfunctional analysissocial sciencessociologydemographyhuman migrationsnatural sciencesbiological sciencesgeneticsgenomes Programme(s) FP4-INCO - Specific research, technological development and demonstration programme in the field of cooperation with third countries and international organizations, 1994-1998 Topic(s) 03010303 - Research on the biology preclinical models of diseases Call for proposal Data not available Funding Scheme CSC - Cost-sharing contracts Coordinator UNIVERSITY OF EDINBURGH EU contribution No data Address King's Building, Darwing Building, Mayfield Road EH9 3Jr EDINBURGH United Kingdom See on map Total cost No data Participants (3) Sort alphabetically Sort by EU Contribution Expand all Collapse all Hasanuddin University Indonesia EU contribution No data Address JL Perintis Kemerdekaan Km 10 90000 Ujung Pandang - Sulawesi Selatan See on map Total cost No data Indian Council for Medical Research India EU contribution No data Address Chandasekharpur 751106 Bhubaneswar See on map Total cost No data LEIDEN UNIVERSITY Netherlands EU contribution No data Address 62,Wassenaarseweg 62 2300 RC LEIDEN See on map Total cost No data
