| Psycho-physiological stress has always been associated with ill health. But in contrast to immunosuppressive chronic stress, short-term acute stress has beneficial, immunoenhancing effects. Experiments contained herein illustrate that acute stress enhances cutaneous immunosurveiIlance by enhancing in vivo leukocyte trafficking into inflamed skin, and thereby promotes inflammatory responses consequent to cutaneous antigen exposure by delivering endogenous adjuvant signals that influence antigen recognition and lymphocyte activation phases of cutaneous cellular immune responses.; In the first set of experiments leukocyte infiltration into a surgical sponge was used to elucidate the kinetics, magnitude, subpopulation-, and chemoattractant-specificity of stress-induced increase in leukocyte trafficking to a site of immune activation. In the second set of experiments, antigen-specific cell mediated immune responses were used to illustrate that acute stress experienced at the time of immunization significantly enhances the immediate innate and subsequent adaptive immune responses in skin ultimately augmenting immunological memory.; To further examine the effects of acute stress on sponge infiltrating leukocytes during cytokine-induced inflammation, lymphotactin (LTN) and Tumor Necrosis Factor-alpha (TNF-alpha) were used. LTN-treated sponges from acutely stressed animals attracted two-fold higher NK and T cells and three-fold higher macrophages while TNF-alpha-treated sponges from acutely stressed animals attracted three-fold higher neutrophils and two-fold higher macrophages than non-stressed animals. These results show that although acute stress initially increases trafficking of all major leukocyte subpopulations to a site of immune activation, tissue damage-, antigen-, or pathogen-driven chemoattractants subsequently determine which subpopulations are recruited more vigorously.; To examine the effects of acute stress on antigen-induced cellular immune response, 2, 4-dinitroflurobenzene, a well-known contact sensitizer was used. During the early 6 h induction phase following immunization, acute stress modulated the inflammatory chemokine and cytokine gene expression in the skin, and enhanced dendritic cell (DC), macrophage and lymphocyte trafficking and activation in the skin and the draining LNs.; Lastly, in another set of studies, mice acutely stressed during primary immunization with keyhole limpet hemocyanin, a model vaccine antigen also showed significantly higher cellular immune response when tested for recall nine months later. At timepoints proximal to immunization, mice acutely stressed showed higher numbers of central memory-like T cells in the draining LNs than non-stressed mice, suggesting a potential mechanism for stress-induced immuno-enhancement. These results suggest that acute stress induces an early shift in the kinetics of leukocyte trafficking and leukocyte activation cascade at the time of primary antigen exposure, and this modulates recall responses during secondary antigen exposure. (Abstract shortened by UMI.)... |
