Abstract
In mammals, the mucosal immune system is a complex network of cells, tissues, and soluble molecules that orchestrate the defense against pathogens or malignant cells; this immune system substantially differs from the one acting at the central level. Nanovaccines have emerged as a promising approach for the development of innovative vaccines, having enhanced immunogenicity and avoiding the use of attenuated/inactivated pathogens. This chapter transmits the essential knowledge on the mucosal immune system required to understand the design and evaluation of nanovaccines, with special emphasis in the function of the nose-associated lymphoid tissue (NALT) and the gut-associated lymphoid tissue (GALT) since the nasal and oral routes are the most explored in nanovaccine development. Antigens administered by mucosal routes are essentially sampled by M-cells, epithelial cells, and dendritic cells; once the antigen reaches the submucosa antigen presenting cells (APCs) it establishes an immune synapse with lymphocytes, which triggers their differentiation and expansion in the lymph nodes. Among the lymphocytes subsets involved in the adaptive immunity, T helper cells are key since they support the response of T and B lymphocytes by producing Th1 and Th2 cytokine profiles, respectively, acquire a Th17 phenotype that contributes to IgA responses, or can rather have suppressive roles by acquiring the regulatory T-cell phenotype (Treg) that is of relevance in therapies against autoimmune or inflammatory conditions. In contrast, T cytotoxic lymphocytes are specialized in killing virus-infected or malignant cells, whereas B mucosal lymphocytes are specialized in antibody production (mainly secretory IgA), which is a key effector mechanism to protect against infectious agents in the mucosa. The use of adjuvants is critical to trigger the desired immune response when mucosal routes are used. Although GALT and NALT share most of the cell types, they differ in the organization and induced immune responses in different mucosal compartments. For instance, intranasal immunization efficiently induces humoral responses in the airways and genital organs, whereas oral immunization induces mainly systemic and intestinal humoral responses, which is explained by the traffic of lymphocytes controlled by homing molecules. The knowledge regarding function and structure of NALT is still limited with respect to GALT. The current knowledge on the mucosal immune system has aided in the development of several nanovaccine candidates and opportunities for designing optimal nanovaccines will be expanded as long as the knowledge on this complex immune system increases in the following years.
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Rosales-Mendoza, S., González-Ortega, O. (2019). The Mucosal Immune System: An Outlook for Nanovaccines Development. In: Nanovaccines. Springer, Cham. https://doi.org/10.1007/978-3-030-31668-6_2
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