HPA System

The Role of Cortisol and the Immune System in Stress

One of the most clinically significant consequences of chronic stress is its effect on immune function. Through sustained elevation of cortisol, psychological stress can suppress immune defences — impairing the body's ability to fight infection, heal wounds, and resist disease. The field of psychoneuroimmunology (PNI) has provided compelling evidence for these connections.

How Cortisol Suppresses Immune Function

Cortisol suppresses immune function through several mechanisms: it reduces the production of lymphocytes (T cells, B cells); it inhibits the activity of natural killer (NK) cells — immune cells that destroy virus-infected cells and cancer cells; it suppresses pro-inflammatory cytokines; and it impairs macrophage function. Short-term, this can be adaptive — it prevents inflammatory responses during acute physical stress. Chronic cortisol elevation, however, leaves the individual persistently vulnerable to infection and impairs wound healing.

Research Evidence: Kiecolt-Glaser et al.

Kiecolt-Glaser et al. (1984) measured NK cell activity in medical students before finals (low stress) and during finals (high stress). NK cell activity was significantly reduced during the examination period — direct evidence that a real-world psychological stressor produces measurable immune suppression.

Kiecolt-Glaser et al. (1995) examined wound healing in carers for relatives with Alzheimer's disease (chronic stressor) versus matched controls. Carers' wounds healed on average 24% more slowly than controls — linking chronic stress to a concrete, clinically relevant biological outcome. Marucha et al. (1998) replicated this: dental students' wounds healed 40% more slowly during examinations than during the summer holiday.

Selye's General Adaptation Syndrome (GAS)

Hans Selye (1936, 1956) proposed the General Adaptation Syndrome — a model of how the body responds to prolonged stress across three stages:

Selye's General Adaptation Syndrome (GAS) Normal Resistance to stress Time / duration of stressor → Stage 1 Alarm Reaction Stage 2 Resistance Sustained coping — resources depleting Stage 3 Exhaustion Resources depleted → illness/death SAM/HPA activate; initial dip then rise Cortisol depleted; immune/organ failure

Stage 1 — Alarm Reaction: the body's initial response to a stressor — resistance drops briefly as homeostasis is disrupted, then rises sharply as the SAM system and HPA axis activate (adrenaline, cortisol release). The organism is mobilised for coping.

Stage 2 — Resistance: the body sustains its coping response — cortisol remains elevated, physiological resources are mobilised. The organism appears to cope, but reserves are gradually being depleted.

Stage 3 — Exhaustion: if the stressor persists long enough, physiological resources are depleted. Cortisol production falters; the immune system fails; organ systems malfunction. In humans, this stage is associated with burnout, serious physical illness, depression, and potentially death.

 Key Takeaways

  • Cortisol suppresses NK cell activity, lymphocyte production, and cytokines. Adaptive short-term; damaging when sustained.
  • Kiecolt-Glaser et al. (1984): NK cell activity significantly lower during medical students' exam period vs pre-exam baseline — real-world stress produces immune suppression.
  • Kiecolt-Glaser et al. (1995): Alzheimer's carers' wounds healed 24% slower than matched controls — chronic stress directly slows wound healing via cortisol-mediated immune suppression.
  • Marucha et al. (1998): dental students' wounds healed 40% slower during exams — replicates exam stress → immune suppression → slower healing.
  • Selye's GAS (1936): three stages — Alarm (SAM/HPA activate; dip then rise in resistance), Resistance (sustained coping; resources depleting), Exhaustion (resource depletion → illness/organ failure).
  • Psychoneuroimmunology (PNI): the interdisciplinary field studying psychological stress, nervous system, and immune function interactions.