Mechanismsofsensitization,diseasedevelopmentand.pptVIP

Mechanisms of sensitization, disease development and desensitization: towards novel approaches for prevention and therapy Ronald van Ree Academic Medical Center, Amsterdam;Immunology: B-cells and antibodies Immunotherapy: mechanisms and monitoring Atopic march: eczema → asthma → rhinitis → asthma? ;Exposure to allergen results in: no response? protective response (“active tolerance”)? sensitization? +/- symptoms?;Ig? B-cell;Ig? B-cell;IgG/A? B-cell;IgG/A? B-cell;IgG1 B-cell;IgG1 B-cell;;Why are IgE responses always so low compared to IgG responses? Half-life of IgE is very short but this can not explain the 1000-fold difference in serum titers. A major cause most likely is the poor generation of memory B-cells for IgE caused by inefficient processing of mRNA for membrane IgE. Circulating IgE is derived from long-lived plasma cells hiding in survival niches like the bone-marrow and inflammatory sites. Two situations: low allergen exposure (e.g. pollen/mite) i.e. a weak Th2 response that will not effectively induce a germinal center necessary for induction of memory B-cells high allergen exposure (e.g. cat, bee venom) i.e. a strong Th2 response that will a generate mature germinal center facilitating induction of memory;Low exposure situation: no memory only plasma cells;Poor expression of membrane form of IgE favors apoptosis resulting in poor memory ;For primary prevention it is of the greatest importance to investigate the dose-response relation between allergen and (the quality) of the immune response. The window of opportunity is of great importance. A high-dose protective effect as observed for cat has so far not been found for house dust mite. For food allergens this is even more debated. The outcome has very significant public health impact. “Promote cats and peanut butter sandwiches early on or not?” ;What is needed to study the dose-response relation between allergen exposure and (the quality of) the immune response? Analysis of