Figure 8.

Model of stress-induced changes in leukocyte distribution. The model integrates the hormone mediators, source organs, kinetics, direction, leukocyte subpopulation specificity, and target organs, of stress-induced changes in blood immune cell numbers (Dhabhar and McEwen, 1997), and is based on data presented here as well as that published in the literature (for review see: (Dhabhar, 1998; Dhabhar, 2009b)). The stressor can be psychological (sensing a predator), physical (exercise / running from predator) or physiological (inflammation), and generally induces the release of norepinephrine (NE), epinephrine (EPI), and corticosterone (CORT). The adaptive/salubrious profile of blood lymphocyte and monocyte (MO) redistribution during stress involves a mobilization/increase (shaded dark upward diagonal) followed by a trafficking/decrease (shaded light downward diagonal) in cell numbers (Dhabhar, 2009b; Rosenberger et al., 2009), while neutrophils show only a biphasic mobilization. In general, early (2 to 30 minutes) during stress, NE and EPI mobilize monocytes, neutrophils, and lymphocytes into the blood from “barracks” like the spleen, marginated leukocyte pool, lung, bone marrow and lymph nodes. However, some leukocyte subpopulations (e.g., CD62L− CTLs or CD62L+ B cells) that are circulating in the blood under resting conditions, may traffic to tissues soon after the beginning of stress. Later (30 to > 120 minutes), overall lymphocyte and monocyte numbers decrease as cells traffic out of the blood and into target organs that include: 1) Active “battlefields” which are sites of wounding, antigen/pathogen entry, de novo immune activation, or ongoing inflammation. 2) Homeostatic surveillance and homing pathways within organs that form the main interfaces between the internal and external environments, i.e., the skin and the mucosal-epithelial linings of the oro-digestive and urogenital tracts. 3) Back to the “barracks” which are sites such as the spleen, lung, bone marrow, lymph nodes to which many immune cells may return during stress. Decreases in blood lymphocytes and monocytes, are largely driven by CORT, and for some subpopulations (CTL & B cells) also by EPI. from the bone marrow and may be driven by NE and EPI, and CORT. It is highly likely that leukocytes with specific functional and/or maturational characteristics (e.g., monocyte vs. neutrophil vs. lymphocyte, inflammatory vs. resident monocyte, naïve vs. memory lymphocyte, mucosa vs. bone marrow directed B cell) traffic to specific targets during stress. If the stress response is accompanied by immune activation then the stress-induced leukocyte redistribution ensures that more leukocytes are present to respond to challenge at sites of ongoing or potential inflammation either by already being present at the site of attack (e.g., inflammatory monocytes, effector T cells, and antibody secreting B cells) or by being available in the blood (e.g., mobilized neutrophils). Using “real world” metaphors, we have suggested that a short-term / fight-or-flight stress response prepares the body's “army” for battle, by inducing a redistribution of the body's “soldiers” from “barracks” to “boulevards” to actual or potential “battlefields” (Dhabhar, 1998; Dhabhar, 2009b). As a result, leukocyte redistribution response is one mechanism through which a short-term stress response facilitates immuno-enhancement in compartments that are enriched with immune cells during/following stress (Dhabhar, 2009b; Dhabhar and McEwen, 1996; Viswanathan et al., 2005; Viswanathan and Dhabhar, 2005).