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Acute stress as a psycho-physiological adjuvant: cellular and molecular mediators of stress-induced enhancement of primary immunization

Viswanathan, Kavitha

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2005, Doctor of Philosophy, Ohio State University, Oral Biology.
Psychological stress has always been associated with ill health. In contrast to immunosuppressive chronic stress, acute stress has immunoenhancing effects. Current experiments illustrate that acute stress enhances leukocyte trafficking into inflamed skin, and thereby promotes short- and long-term cutaneous antigen-specific responses. Acute stress enhanced the kinetics, magnitude, subpopulation-, and chemoattractant-specificity of leukocyte trafficking to a site of immune activation. C57BL6 mice acutely stressed (STR, 2.5h restraint) before subcutaneous sponge implantation showed 200-300% higher neutrophil, macrophage, NK and T cell infiltration than non-stressed (NS) mice within the saline-treated sponges. Lymphotactin-treated sponges from STR mice attracted two-fold higher NK and T cells and three-fold higher macrophages while Tumor Necrosis Factor-alpha-treated sponges attracted three-fold higher neutrophils and two-fold higher macrophages than NS mice, suggesting that although acute stress initially increases trafficking of all major leukocyte subpopulations to a site of immune activation, tissue damage-, and antigen-driven chemoattractants subsequently determine which subpopulations are recruited more vigorously. Antigen-specific cellular immune responses were used to illustrate the immunoenhancing effects of short-term/acute stress on the immediate innate and subsequent adaptive immune responses. During the early 6h and peak 24h induction phase, acute stress modulated the inflammatory chemokine and cytokine gene expression, and enhanced DCs, macrophage and T cell trafficking and activation within the antigen-exposed skin and draining LNs. During the early 6h and peak 24h elicitation phase, STR mice showed increased effector-memory T cell recruitment within the antigen-exposed skin, coupled with significantly upregulated Type1 cytokine gene expression, and an early increase in IFNg-positive T cells in the draining LNs than NS mice. STR mice also showed increased numbers of central memory–like T cells in the draining LNs immediately following immunization, suggesting a potential mechanism for stress-induced immuno-enhancement that lasted for 9 months post-immunization. In summary, these results show that acute psycho-physiological stress: (i) imparts potent immunostimulatory effects on cutaneous immunity; (ii) enhances the recruitment and activation of critical molecular and cellular components of both innate (DCs and macrophages) and adaptive (T cells) immunity at the cutaneous site of primary antigen exposure and draining LNs; and (iii) induces long-term immunoenhancement by modulating immunological memory.
Firdaus Dhabhar (Advisor)
206 p.

Recommended Citations

Citations

  • Viswanathan, K. (2005). Acute stress as a psycho-physiological adjuvant: cellular and molecular mediators of stress-induced enhancement of primary immunization [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1109785823

    APA Style (7th edition)

  • Viswanathan, Kavitha. Acute stress as a psycho-physiological adjuvant: cellular and molecular mediators of stress-induced enhancement of primary immunization. 2005. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1109785823.

    MLA Style (8th edition)

  • Viswanathan, Kavitha. "Acute stress as a psycho-physiological adjuvant: cellular and molecular mediators of stress-induced enhancement of primary immunization." Doctoral dissertation, Ohio State University, 2005. http://rave.ohiolink.edu/etdc/view?acc_num=osu1109785823

    Chicago Manual of Style (17th edition)