Fig. 1
Formation of the mucosal barrier in the respiratory tract and its functions in the immune system. When pathogens invade, respiratory mucosal immunity can impede pathogen invasion and prevent further dissemination through three stages: physicochemical barrier, innate immune responses, and adaptive immune responses. I. The physicochemical barrier is composed of mucus and epithelial cells. Mucins and sIgA in the mucus can neutralize pathogens and expel them from the respiratory tract through the clearance action of ciliated cells. Pathogens that breach the mucus layer interact with epithelial cells, which release cytokines or engage in direct cell-to-cell contact (gap junctions, exosomes, etc.) to activate innate immune cells. II. After penetrating the physicochemical barrier, pathogens enter the lamina propria. Professional cells in the lamina propria (DCs, macrophages, mast cells) recognize PAMPs to initiate signal cascades, recruiting more innate immune cells to participate in the antiviral response. PRRs activate adapter proteins, triggering cascades that activate IRFs and NF-κB. These factors translocate to the nucleus, initiating interferon gene transcription and enhancing immune defense. III. During the adaptive immune phase, T cells and B cells play dominant roles. DCs that have encountered pathogens present antigens and transmit stimulatory signals to T cells and B cells. Antigen-presenting cells promote the maturation and proliferation of naïve CD4⁺ and CD8⁺ T cells through T cell receptor (TCR) engagement and co-stimulation (CD80/CD86). After antigen recognition, B cells differentiate into antibody-secreting plasma cells and memory B cells with the help of cognate CD4⁺ Tfh cells. IV. Effector cells migrate from the induction site to the effector site to exert their functions. DCs, dendritic cells; ILCs, innate lymphoid cells; IRFs, interferon regulatory factors; NF-κB, nuclear factor-kappa B; IFNs, interferons; Th cell, T helper cell; M cell, microfold cell; MUC5AC, mucin 5AC; MUC5B, mucin 5B; IgA, immunoglobulin A; sIgA, secretory Immunoglobulin A; CTL, cytotoxic T lymphocyte; TRM, tissue-resident memory T cell