Common mucosal immunity plays an important role in host protection against infectious diseases. Secretory immunoglobulins reduce microbial and viral growth, and decrease adherence and colonization of microorganisms to host mucosal sites. Our studies indicate that the skin can serve as an effective site for the induction of common mucosal immunity under certain circumstances. We have demonstrated that the subcutaneous immunization of naive animals with an antigen plus alpha,25(OH)2d3 induces both common mucosal and systemic immune responses. Peyer's patches are the primary lymphoid organ inductive site for these skin-induced mucosal responses, identical to what occurs following an oral immunization. This was deduced by analysis of germinal center development and lymphoid tissue sites of antibody producing cells. We recently found that dendritic cells (DC) pulsed with antigen and treated with 1alpha,25(OH)2d3, induced mucosal and systemic immune responses following their injection into footpads of naive recipients. Our objectives are now to examine those conditions which are essential for the induction of mucosal and systemic immune responses following the administration of antigen-pulsed DC to immunologically naive recipients. We will investigate whether antigen-pulsed DC can effectively promote germinal center development in classical mucosal immunity inductive sites following their pretreatment with 1alpha,25(OH)2D3, and determine how such treatments alter the homing properties of the injected cells. We will evaluate if such enzyme induction may represent a natural way to promote mucosal immunity to antigens delivered via the skin. Newborns and the elderly are highly susceptible to gastrointestinal and respiratory diseases normally controlled by mucosal defenses. We will study the protective properties in offspring of passively acquired induced in mothers by systemic immunization with antigens plus 1alpha,25(OH)2D3. We will also investigate intervention strategies which restore mucosal immune competence to aged animals. Our studies could uncover novel characteristics about the mammalian immune system and its flexibility in regulating particular forms of effector responses.
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