What do the immune system and the brain know about each other?

The immune system is generally viewed as being regulated by a variety of mechanisms 'from within'. This internal regulation is conceived to be mediated by different subsets of T cells, by antibodies including their idiotypic determinants, monokines, yphokines, etc., which appear in a given sequence and quantity. This autoregulation confers a high degree of autonomy on the immune system. However, processes essentialfor thefunctioning of immunological cells, such as metabolism, transport of substances, allosteric changes in membranes, lymphoid cell proliferation and transformation, and lymphokine synthesis (for bibliography, see Ref. 1), are affected by several hormones and neurotransmitters. These facts constitute by themselves good arguments for another kind of regulation, one 'from without' (a term used by Medawar in 1973) which is, as Hugo Besedovsky, Adriana del Rey and Ernst Sorkin have proposed, superimposed upon and interwoven with autoregulation. This postulate requires the existence of information channels between the immune system and the central nervous system, i. e. that they should know about each other. The apparently lofty title of this presentation raises a number of critical questions about the workings of the immune system in its natural environment. Here the authors discuss these questions: What do immune cells know about the brain? What does the brain know about the immune system? How do the brain and the immune system communicate with each other? Are brain-immune system interactions linked in regulatory feedback circuits?