Aim. To investigate morphological, functional and immunophenotypic features of the immune response using mucosal and parenteral methods of administration of the complex of opportunistic microorganism antigens. Materials and methods. Functional, morphological and immunophenotypic characteristics of immunocompetent cells and organs of mice (80, SWA line) in intact animals (control), as well as the above characteristics in intranasal (3-fold in the dose of 500 ug / mouse), peroral (3-fold in the dose of 2 mg / mouse) and subcutaneous (2-fold in the dose of 200 mg / mouse), methods of administration of multicomponent vaccine Immunovac VP-4 containing the complex of opportunistic microorganism antigens were investigated. Mononuclear leukocytes of spleen, lymph nodes and lymphoid tissue of the small intestine were used to evaluate the expression level of markers (CD3, NK 1.1, CD3/NK, CD4, CD25, CD4/CD25, CD8, CD19, MHC II, CD5.2 (B1), TCR (Tγδ) with the help of monoclonal antibodies («Caltag Laboratories», USA) by means of a flow cytometer FacsCalibur («Beckman Coulter F-500", USA). Cytotoxic activity of natural killers against neoplastic K562 line in MTT assay was revealed. Morphological studies were performed on serial paraffin sections stained with histological and histochemical methods. Statistical processing of the data was performed using statistical package StatSoft 8.0. Results. It was revealed that the investigated complex of opportunistic bacteria antigens causes significant activation of effectors of innate immunity both in parenteral and mucosal immunization. It is displayed in increased levels of expression of differentiation, co-stimulating, adhesive molecules on the surface of mononuclear leukocytes, in proliferation of key effectors of mucosal immunity (Tγδ-B 1 and B- lymphocytes, NK cells), increase in their functional activity, changes in the pattern, cellular composition of immunocompetent organs and lymphoid tissue, regional to the site of administration and distant from it that indicates formation of not only local, but systemic immunity as well. Conclusion. The obtained data allow us to extend the strategy for using vaccines and immunomodulators of bacterial origin by means of non-parenteral immunization methods to create protection from a broad spectrum of pathogens.