Although early research suggested that allergic reactions could be provoked with artificial roses, and hay fever attacks could similarly be stimulated by exposure to pictures of hay fields, Ader and Cohen's (1975) demonstration that immunosuppression could be conditioned to a novel stimulus provided the first empirical investigation of the relationship between behavior and the immune system. In their landmark study, Ader and Cohen paired the novel taste of saccharin with the immunosuppressive agent cyclo-phosphamide in a taste aversion paradigm. Subsequent presentation of saccharin resulted in an attenuated immune response to sheep red blood cells. These results suggested that the immune system should be viewed as an integrated physiological system subject to the influence of psychosocial and environmental factors and not, as previously thought, an autonomous system operating relatively independently of other physiological processes. These findings were replicated and extended in both human and animal studies and led to the development of the field of psychoneuroim-munology. Subsequent research has provided extensive evidence for the relationship between stress and immune alterations and has examined possible mechanisms through which psychosocial factors could lead to altered immune activity. In addition, moderators of the stress-immune system relationship and the role of stress-induced immunosuppression in various disease processes have been studied.
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