Enhancing versus Suppressive Effects of Stress on Immune function. Implications for Immunoprotection and Immunopathology

Firdaus S. Dhabhar

Research output: Contribution to journalReview articlepeer-review

12 Scopus citations


It is widely believed that stress suppresses immune function and increases susceptibility to infections and cancer. Paradoxically, stress is also known to exacerbate allergic and autoimmune diseases that are proinflammatory and should theoretically be ameliorated by immunosuppression. These observations suggest that stress may have bidirectional effects on immune function, elucidation of which may have significant clinical consequences. It has recently been shown that in contrast to chronic stress that suppresses or dysregulates immune function, acute stress can be immunoenhancing. Studies have shown that acute stress experienced at the time of immune activation can affect dendritic cell, neutrophil, macrophage, and lymphocyte trafficking, maturation, and function, and augment innate as well as adaptive immune responses. Acute stress experienced prior to novel antigen exposure enhances innate immunity and memory T-cell formation and results in a significant and long-lasting immunoenhancement. Acute stress experienced during antigen re-exposure enhances secondary/adaptive immune responses. Therefore, depending on the conditions of immune activation and the nature of the immunizing antigen, acute stress may enhance the acquisition and expression of immunoprotection or immunopathology. In contrast, chronic stress dysregulates innate and adaptive immune responses by shifting the immunological balance from Type 1 to Type 2 cytokine-mediated immunity, and suppresses immunity by decreasing leukocyte numbers, trafficking, and function. Chronic stress also increases susceptibility to non-melanoma skin cancer by suppressing Type 1 cytokines and protective T cells while increasing suppressor T-cell function. We have suggested that the adaptive purpose of a physiological stress response may be to promote survival, with stress hormones and neurotransmitters serving as beacons that prepare the immune system for potential challenges (e.g., wounding or infection) perceived by the brain (e.g., detection of an attacker). However, this system may exacerbate immunopathology if the enhanced immune response is directed against innocuous or self-antigens, or dysregulated following prolonged activation during chronic stress. In view of the ubiquitous nature of stress and its significant effects on immunoprotection as well as immunopathology, it is important to further elucidate the mechanisms mediating stress-immune interactions and to meaningfully translate findings from bench to bedside.

Original languageEnglish (US)
Pages (from-to)207-224
Number of pages18
JournalNeuroImmune Biology
Issue numberC
StatePublished - 2007
Externally publishedYes

ASJC Scopus subject areas

  • Immunology
  • Neurology
  • Clinical Neurology


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