central nervous system to induce illness/sickness behaviors (Fleshner et al., 1997).

Stress mediators associated with personal ties can be protective and adaptive as well as damaging. For example, significantly larger numbers of leukocytes were found in the skin of stressed animals both before and after experimental introduction of antigen (Dhabhar and McEwen, 1999), suggesting that stress prepared the immune system to respond to challenges such as infection. The bidirectional effects of stress on skin immunity are mediated by the adrenal hormones corticosterone and epinephrine. However, while acute stress is immunoenhancing, chronic stress is immunosuppressive (Dhabhar and McEwen, 1997; Dhabhar et al., 1995).

The chronic stress of caring for a relative with dementia was linked with elevated SAM and HPA activation and diminished immune function, such as reduced proliferative responses of peripheral blood leukocytes (Kiecolt-Glaser et al., 1991), lower natural killer cell response (Esterling et al., 1994), and impaired antibody response to influenza virus vaccine (Kiecolt-Glaser et al., 1996). Similar results have emerged from studies of the effects of psychosocial stress on vaccine responses. Using the stress of taking a university examination (Glaser et al., 1992) or the chronic stress of being a caregiver (Kiecolt-Glaser et al., 1996; Glaser et al., 1998), the response to vaccination was examined during the stressful period. In both cases, vaccine responses were attenuated in the stressed groups. Caregivers of relatives with progressive dementia have also shown impaired wound healing relative to controls matched for age and family income (Kiecolt-Glaser et al., 1995, 1998).

Alteration of immune function has been observed among persons in marital conflict (Kiecolt-Glaser et al., 1987). Specifically, negative or hostile behaviors during a marital conflict produce greater and/or more persistent alterations in autonomic activation and circulating stress hormones. Couples characterized by high, relative to low, negative behaviors during a marital conflict also show greater decrements over the 24 hours of study on natural killer cell lysis, the blastogenic response to two mitogens, and the proliferative response to a monoclonal antibody to the T3 receptor (Kiecolt-Glaser et al., 1994).

In an experimental study of stress and infectious illness, healthy volunteers reported their level of stress and were exposed to saline or one of several strains of respiratory virus (Cohen et al., 1991). Following inoculation, subjects were quarantined and monitored for the development of respiratory illness. After seven days of quarantine, each participant was classified as not infected, infected but not ill, or infected and ill. No