How does the innate immune system interact with the acquired immune system?
If innate immunity cannot handle the invading foreign antigen or microbe, then adaptive immunity responds. APCs in the tissue (e.g., skin, lung, and mucus membranes) endocytose antigen, becoming activated and upregulating the trafficking chemokine receptor CCR7 that causes migration toward the ligand CCL21 produced in the lymphoid tissues (e.g., spleen, lymph nodes, mucosal-associated lymphoid tissue [MALT]). In those lymphoid tissues, the adaptive immune response develops.
Antigen that has been endocytosed by APCs is processed in the endoplasmic reticulum where it is loaded onto MHC class I or II molecules depending upon the type of antigen. (See Question #18 below for more about MHC.) The MHC-antigen complex is then presented on the APC surface. Simultaneously, signals through TLRs and/or PRRs cause the APCs to upregulate costimulatory molecules such as CD80 (B7-1)/CD86 (B7-2) or CD40 on the cell surface. T cells within the lymphoid tissue recognize the MHC-presented antigen using the TCR as well as the costimulatory molecules using CD28 or CD40L, respectively. Both signals, the TCR (signal 1) and costimulation (signal 2), are required for T-cell activation. Note that self-antigens are not recognized by TLR/PRRs of the innate immune system and, therefore, do not induce the mandatory costimulatory molecules (signal 2) on APCs needed to activate T cells, ensuring that only pathogen-specific T cells are activated. Activated T cells then regulate B cells, other T cells, and other cells participating in the immune response.