English: (A) The lymphatic system does not just act as passive conduits for lymph but also plays an active role in innate and adaptive immune responses. For example, during wound healing an inflammatory response is initiated, and skin resident macrophages phagocytose invading microorganisms to clean the wound. Dendritic cells (DCs) are central to the initiation of primary immune responses by presenting the pathogenic antigens (red dots) on their surface. Chemokines released by LECs attract and direct the DCs towards the initial lymphatics (lymphatic capillaries). The DCs actively squeeze through the endothelial flaps (primary valves) created by the discontinuous button-like endothelial junctions. When inside the initial lymphatic, the DCs crawl along the lymphatic endothelial surface also guided by a chemokine gradient. On entering the lymphatic collector vessels, the DCs are transported passively in the direction of lymph flow to the lymph nodes where they initiate adaptive immunity. Thus, the positioning of lymph nodes along lymph drainage pathways (Figure 1), allows particles to be filtered and the lymph fluid to be screened for foreign material, particularly antigen from microbes, to induce specific immune reactions. (B) In a mature lymph node, we can distinguish three main regions: the cortex, the paracortex and the medulla. Naive lymphocytes enter lymph nodes mainly via the blood (High Endothelial Venules, HEVs) but also via afferent lymphatics. HEVs are specialized blood vessels responsible for the supply of naive lymphocytes to the lymph node. After crossing the endothelium of the HEVs into the lymph node (see insert), lymphocytes migrate to distinct areas, the B- and T-cell zones; CXCR5-expressing B-cells migrate towards CXCL13 secreted by follicular DCs, and CCL19 expressed by DCs attract T-cells via CCR7 receptors. A highly orchestrated process involving antigenic presentation by the DCs then turns naive lymphocytes into activated lymphocytes. Activated immune cells (effector cells) will leave the lymph node through the efferent lymphatics towards the next lymph node for further immune refinement until eventual discharge back into the blood circulation. Arrows indicate direction of flow.