of the Immune System
Alexander W. Kusnecov
Rutgers, The State University of New Jersey
The past two decades have witnessed the growth of a multidisciplinary research area centered around the notion that the brain, through the neuroendocrine system., modulates the immune system, while the immune system in turn modulates the brain. The various converging lines of evidence supporting this concept have been summarized elsewhere (Ader, Felten, & Cohen, 1991). However, serving as the basis for the present chapter is one of the most compelling demonstrations of brain-immune system interactions: behaviorally conditioned immunomodulation. This phenomenon is based on the observation that alterations of immune function can be linked in a learned manner to a conditioning stimulus (CS), such that the CS attains the power to reenlist the immunological change with which it had previously been associated. In the terminology of the conditioning literature, the inducer (e.g., immunosuppressive drug) of the immunological alteration may be viewed as the unconditioned stimulus (UCS), whereas the reenlisted immunological alteration after reexposure to the CS is a conditioned response (CR). Thus, not unlike the traditional Pavlovian conditioning of the salivary response in hungry dogs, the activity of the immune system can also be manipulated by conditioning.
Not surprisingly, the concept of conditioning the immune system first emerged from the former Soviet Union during the first half of the 20th century. Conducting research in laboratory animals, and examining the modulation or elicitation of specific and nonspecific host defenses within classical Pavlovian conditioning paradigms, results were obtained that suggested the immune system could be classically conditioned. Unfortunately, many of the studies were poorly reported and badly controlled (for a detailed review of these studies see Ader, 1981). More recently, Ader and Cohen (1975) demonstrated a conditioned immunopharmacologic effect on the antibody response in rats, and initiated the modern era of research on conditioning of the immune system. In doing so, they suggested in almost heretical fashion a possibly “learned” functional alteration in a biological system- the immune system-that presumably had been thought to function independently of the central nervous system (CNS). This implication was received with considerable skepticism, but spurred by a rapid accumulation of knowledge in the brain, behavioral, and immunological disciplines, it has gained general acceptance (Ader et al., 1991; Kusnecov & Rabin, 1994).
Much of the literature on behavioral conditioning of the immune system has been reviewed in detail elsewhere, with considerable emphasis on such issues as the generality of conditioning paradigms, conditioned and unconditioned stimuli, and immunological measures (Ader & Cohen, 1991; Kusnecov, Husband, & King, 1988). Therefore, this chapter tries to avoid detailed descriptions of studies already reviewed, and focuses more on recent and clinically applicable observations. A brief overview of the immune system is provided in the next section for those readers unfamiliar with immunology.
The immune system is a diffuse collection of specialized cells that function to protect the body (the host) from infection