Abstract <p>The results of long-term research on studying the mechanisms of regulatory functions of free receptors of immunocompetent cells in ensuring immune homeostasis in different climatic and geographical conditions are presented. Overall, 1316 practically healthy at the time of examination people aged from 21 to 55 years, 1024 women and 292 men, residents of Arkhangelsk, Murmansk, Nenets Autonomous Okrug, and Svalbard Archipelago were examined. On the basis of the obtained data the cellular-humoral concept is proposed: the shedding of receptor structures from the cell membrane (CD16, CD23, CD25, CD71, CD54, CD56, CD62L, CD80, and CD95) is a physiological mechanism of restriction of the functions performed by the receptor; it occurs simultaneously with the formation of the corresponding membrane forms, which provides adequate and timely levels of activation, differentiation, and apoptosis of lymphocytes during the periods of their functional activity. Shedding creates an opportunity to restore cell potential to baseline for subsequent activity: an increase in the concentration of extracellular co-stimulatory molecules (sCD71 and sCD25) is associated with a decrease in circulating lymphocytes with appropriate receptor structures on the membrane (CD71+ and CD25+). The extracellular pool of receptor structures participates in the transport and clearance of lymphocyte activation products with the formation of immune and non-immune circulating complexes, contributing to their clearance.</p>