Vertebrate development and growth are regulated by systemically acting hormones, by cell-to-cell and cell-to-matrix interactions and by locally induced mediators (cytokines). Accordingly, three categories of signal may be distinguished as shown:

(1)The competence signal will enable the cell to react to additional signals. It is proposed that for most tissues and organs, GH or some other members of the GLH, such as PRL or PL, will deliver this signal.

(2) The second group of signals is delivered by cell-to-cell and cell-to-matrix interactions. Adhesion molecules interacting with their respective counterparts on other cells, or with matrix determinants, and membrane- and matrix-bound growth factors are involved in the generation of these non-diffusible regulatory signals which mediate positional regulation, i.e. determine whether or not the cell will divide, differentiate, function, or perhaps undergo apoptosis, according to the physiological requirements at the site where the cell is located in the body.

(3) The third signal is delivered by locally produced soluble mediators (cytokines) and concludes the signalling cascade that leads to the assignment of function to each particular cell according to its stage of differentiation and position.

Current information indicates that there is redundancy at all three levels of cell signalling The immune system is regulated according to the above scheme where PRL and GH act as the hormones of immunocompetence enabling lymphoid cells to react to antigen.

Antigen receptors belong to the immunoglobulin family of adhesion molecules and thus deliver the second signal.

Lymphocytes express a number of other adhesion molecules that contribute to the regulation of immune reactions. Some of these adhesion molecules also mediate lymphocyte homing and recirculation.

Interleukins and/or other lymphokines complete the cascade of lymphocyte signalling which leads to cell proliferation, differentiation into effector cells and function.

Additional hormones and neurotransmitters contribute to immunoregulation, mostly by signal modulation, which allows for the fine-tuning of the immune system, so that it is able to function in homeostasis and harmony with the organism.

 For further details, please see the original paper in Neuroimmunomodulation, 1994;1:201-215)Abstract 

Also view article in Neuroimmune Biology: Vol 3: The Immune-Neuroendocrine Circuitry: 
History and Progress ,NIB 2003;3 pp281-299)  
Immunocompetence .(Istvan Berczi and Andor Szentivanyi, editors)

Hans Selye's Contributions to Neuroimmune Biology	Top	Curriculum Vitae