This review will highlight our current understanding of the formation, circulation, and immunological role of lymphatic fluid. The formation of the extracellular fluid depends on the net balance between the hydrostatic and osmotic pressure gradients effective in the capillary beds. Lymph originates from the extracellular fluid and its composition combines the ultrafiltrated plasma proteins with the proteome generated by the metabolic activities of each parenchymal tissue. Several analyses have indicated how the lymph composition reflects the organs' physiological and pathological states. The collected lymphatic fluid moves from the capillaries into progressively larger collectors toward the draining lymph node aided by the lymphangion contractility and unidirectional valves, which prevent backflow. The proteomic composition of the lymphatic fluid is reflected in the MHC II peptidome presented by nodal antigen-presenting cells. Taken together, the past few years have generated new interest in the formation, transport, and immunological role of the lymphatic fluid.
