Network regulation of the immune response: Alternative control points for suppressor modulation of effector lymphocytes

The network theory of the immune response proposed by Jerne has stimulated considerable interest, and a large body of evidence supporting this theory has been produced. However, the structure and function of the immune network have not been precisely defined. In this paper we develop several criteria to compare alternative systems on the basis of function and then examine mathematically the functional significance of two interactions involving suppressor regulation of effector lymphocytes in normal immune responses. The interactions examined in detail are suppressor regulation of the production of effector lymphocytes and suppressor regulation of the clearance of effector lymphocytes. The approach is one that has been used previously to predict and characterize function and design in biochemical and genetic control systems. The results of our analysis suggest that an immune system with suppressor regulation of the production of effector lymphocytes is equal or superior to a system without this form of regulation on the basis of all of the criteria examined in this study. Also, a system with regulation of the clearance of effector lymphocytes can be equal or superior to a system without this form of regulation on the basis of six criteria, but it is inferior to such a system on the basis of one criterion. Furthermore, a system with regulation of both production and clearance of effector lymphocytes is equal or superior to a system without regulation of production on the basis of all of the criteria and can be equal or superior to a system without regulation of clearance on the basis of six criteria, but it is inferior to such a system on the basis of one criterion. Similar conclusions hold for the comparison of systems in which regulation is exerted upon the production or clearance of effector molecules, such as antibodies or free radicals.