The brain and the immune system communicate with each other by sharing the signal molecules and receptors. While the brain modulates immunity through the neuroendocrine and autonomic nervous controls, the immune system signals the brain by means of cytokines. This paper gives a brief review on our recent findings on (1) the central neural circuits involved in the stress-induced immunosuppression, (2) the roles of the sympathetic nerve innervating the spleen as a communicating channel from brain to immune system, and (3) the role of the organum vasculosum lamina terminalis region as a site of blood-brain signal transduction. Particularly, we have revealed that an inescapable stress elicits an activation of brain opioid systems which leads to an enhanced activity of the splenic sympathetic nerve through the brain CRF system and thereby suppresses the splenic natural killer cytotoxicity by beta-adrenergic mechanisms.