Lymphocyte Trafficking from Inductive Sites to Effector Sites

Th e initiation, maintenance, and resolution of innate and adaptive immune responses are critically dependent on immune cell migration, not only within tissues but often over long distances between organs. Th is process is highly dynamic and requires that immune cells interact with multiple vascular, lymphatic,and tissue environments in a tightly controlled and organized fashion. Most infections will initially constitute a small number of pathogens and be localized to a small tissue area. If naive lymphocytes were tissue-resident cells dispersed at random throughout the body, the chances that a given antigen specific lymphocyte would be at the right site—that is, at the site of pathogenentry—would be very slim. In a rough calculation, we might estimate that a T lymphocyte with a diameter of 10 μm and a volume of about 0.5 × 10⁻¹⁸ m³occupies less than 10−15% of the body volume. Even if we suppose that several hundred T lymphocytes recognize a distinct antigen, the odds of an antigen-specific lymphocyte’s being in the same location as a pathogen remain extremely low. Lymphocyte recirculation solves this problem by enabling the entire T lymphocyte population to scan antigen-presenting cells within lymphoidcompartments.Perhaps nowhere is this more obvious than during the induction of adaptive immune responses. Adaptive immunity is initiated when antigen-presenting cells, primarily dendritic cells (DCs), present antigen to lymphocytes in inductive immune compartments, such as lymph nodes and Peyer’s patches. During mucosal immune responses, antigen-bearing DCs migrate from mucosal tissues through draining afferent lymph vessels to regional lymph nodes and intothe lymph node T-cell zone. Conversely, to find a DC presenting relevant cognateantigen: major histocompatibility complex (MHC), naive lymphocytes continually traffic from the bloodstream into lymph nodes and back via efferent lymph to the venous blood. In combination, these migratory routes of DCs and lymphocytes allow frequent contact of both cell types and thus form the basis for the efficient induction of adaptive immune responses. Besides the constitutive recirculation of naive lymphocytes, immune cells need to be directed to sites of inflammation. Th is holds true for cells of theinnate immune system, including monocytes and granulocytes, which are rapidly recruited to the inflamed tissue during the initial phase of an immunereaction, and also for effector T cells and plasma cells, which are generated inthe adaptive immune response.