factors alter the activity in structures that project to the top of the central nucleus of the amygdala (Sotres-Bayon et al. 2006), underscoring the amygdala as the key integrative site for fear.
In contrast, much remains to be learned about the neural control of defense responses to threat. For example, depending on circumstances, external threats such as the presence of a predator may result in flight, freezing, or other defensive behaviors. While the involvement of the midbrain periaqueductal gray is well known (Keay and Bandler 2002), inactivation of the brain areas typically responding to a threat from a predator reduces the defense response(s) elicited by predator odor or exposure (Blanchard et al. 2005; Canteras 2002), which may differentially impact predator defense and shock stimuli responses.
The relationship between stress, distress, and the immune system is very complex. Acute stress usually activates innate immune responses (i.e., nonspecific immunity), but it may either increase or inhibit adaptive immunity. On the other hand, chronic stressors suppress adaptive immune responses. Activation of various types of immunity-related cells may be used as an indicator of immune system-stress interaction.
Signaling pathways link the brain with the immune system thereby allowing stress and distress to influence immune function. Immune system cells such as lymphocytes and macrophages express receptors for a variety of hormones and neurotransmitters, while the spleen and thymus are innervated by the autonomic nervous system (Felten et al. 1985; Sanders et al. 2001). The complex nature of these influences, however, does not permit simple generalizations such as “stress/distress suppresses immune function”. The immune responses elicited depend on the type, duration, and intensity of the stressor; the species, strain, age, and gender of the animal(s); and the aspect of immunity examined.
The principles that determine whether acute stressors inhibit or potentiate adaptive immunity are currently unknown. Nevertheless, adaptive immune responses that involve antigen recognition by T cells are invariably affected in acute stress. As Fleshner and colleagues have shown, rats stressed by inescapable tail shock failed to expand a subset of T cells and produced reduced quantities of IgM and IgG antibodies (Fleshner et al. 1995). In contrast, restraint at the time of immunization was shown to facili-