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The reticuloendothelial system is designed to trap foreign antigens that have penetrated the body and to subject them to ingestion and degradation by the phagocytic cells of the system. Also, there is constant movement of lymphocytes throughout the body, and this movement permits deposition of lymphocytes in strategic places along the lymphatic vessels. The system not only traps antigens but also provides loci (the secondary lymphoid organs) where antigen, macrophages, T cells, and B cells can interact within a very small area to initiate an immune response.

Figure 2.14. Circulation of lymph and fate of antigen following penetration through: (1) bloodstream, (2) skin, and (3) gastrointestinal or respiratory tract.

The fate of an antigen that has penetrated the physical barriers and the cellular and antibody components of the ensuing immune response are shown in Figure 2.14. Three major routes may be followed by an antigen after it has penetrated the interior of the body.

 Antigens may enter the body through the bloodstream. In this case, they are carried through circulatory system to the spleen where they interact with APCs, such as DCs and macrophages. As discussed earlier, a major function of these APCs is to take up, process, and then present components of the antigen to the T cells that express the appropriate antigen‐specific TCR. This interaction, together with the other co‐stimulatory signals derived from cell–cell interaction, activates the T cells. Splenic B cells expressing antigen‐specific BCRs are also activated following exposure to antigen, a process facilitated by the cytokines produced by antigen‐activated T cells.

 Antigens may lodge in the epidermal, dermal, or subcutaneous tissues to stimulate inflammatory responses. From these tissues, the antigen, either free or trapped by APCs, is transported through the afferent lymphatic channels into the regional draining lymph node. In the lymph node, the antigen, macrophages, DCs, T cells, and B cells interact to generate an immune response. Eventually, antigen‐specific T cells and antibodies, which have been synthesized in the lymph node, enter the circulation and are transported to the various tissues. Antigen‐specific T and B cells and antibodies also enter the circulation via the thoracic duct.

 The antigen may enter the gastrointestinal or respiratory tract, where it lodges in the MALT or BALT, respectively. There it will interact with macrophages and lymphocytes. Antibodies synthesized in these organs are deposited in the local tissue. In addition, lymphocytes entering the efferent lymphatics are carried through the thoracic duct to the circulation and are thereby redistributed to various tissue.