Coordinated host defense through an integration of the neural, immune and haemopoietic systems

Interactions between the neural and immune systems exist through humoral factors operating via the hypothalamic-pituitary-adrenal axis and cytokines acting over a relatively long distance. Anatomical evidence also suggests direct, hard-wired pathways of interaction and control through innervation of lymphoid organs and peripheral sites involved in host defense, including the thymus, spleen, lymph nodes, and skin. Recent evidence has demonstrated: 1) neural control of the bone marrow haemopoietic system, 2) interactions between peripheral nerve endings in the skin and epidermal Langerhans cells, and 3) peripheralization of leukocytes in the initial stages of stress. This leads us to propose that the nervous system is involved in host monitoring and coordination of host defense systems. If the brain is to have appropriate control of host defense mechanisms it must have: (a) afferent inputs monitoring host defense status, (b) efferent control pathways that modulate primary reactions to infection and damage, (c) efferent activation pathways to the myeloid defense system while the specific, lymphoid immune system is activated, and (d) inhibition of the proliferative lymphocytic response if the infection has been dealt with. We are investigating whether such a model, which allows for control and coordination of both the initial myeloid defense system and of the acquired immune response, is observed in mammals.