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Lymph nodes are the central hubs in which innate and adaptive immunity coordinate productive immune responses. They are highly organized structures strategically placed at intersections between draining lymphatics and the circulating blood vasculature. Upon encountering and processing pathogens in the periphery, innate immune cells such as DCs migrate to nearby lymph nodes. Migration of cells towards and within lymph nodes has been expertly reviewed previously [67]; resident innate immune cells, including macrophages, are poised to respond immediately in the case of pathogen entry, or relay immune information further into the lymph node. T cell and B cell zones in the inner cortex are spatially organized and surrounded by macrophages. Lymphocytes enter through high endothelial venules, guided by fibroblastic reticular cells. Here, they scan migratory DCs for cognate antigen. T and B cells that are continuously circulating and patrolling the body migrate through these lymph nodes and upon encountering a DC-presented cognate antigen, clonally expand and mount a massive and highly-specific adaptive immune response with the purpose of eradicating the microbial pathogen and generating long-lasting immunity. In order for this entire process to be successful, many coordinated events must be executed successfully.

Proper function of lymph nodes requires intense cross-talk between hematopoietic cells and the stroma. Accumulation of lipid droplets and increased fibrosis are common features of the disrupted lymph node architecture and disrupted spatial organization associated with aging [68, 69]. These structural changes not only impair physical communication between lymphocytes and the lymph node stroma, but also probably perturb the environment and disrupt normal homeostasis within the lymph node. Multiple studies have reported reduced lymphocyte cellularity of aged lymph nodes both during the basal state and during infection [52, 68, 70]. Disrupted organization of T cell and B cell zones in the aging lymph node further compounds the diminished immune response and may explain, in part, lower-magnitude T cell responses and lower antibody responses after infection or vaccination in the elderly.