Urban traffic is subject to disturbances that cause long queues and extended waiting times at signalized intersections. Although Multi-Agent Systems (MAS) were considered to control traffic at signalized intersections in a distributed way, their generic conceptual framework and lack of built-in adaptation mechanisms prevent them from achieving specific disturbance management capabilities. The traffic signal control problem is still a challenging open-ended problem for which learning and adaptation mechanisms need to be developed to deal with disturbances in an intelligent way. In this article, we rely on concepts and mechanisms inspired by biological immunity to design a distributed, intelligent and adaptive traffic signal control system. We suggest a heterarchical multi-agent architecture, where each agent represents a traffic signal controller assigned to a signalized intersection. Each agent communicates and coordinates with neighboring agents, and achieves learning and adaptation to disturbances based on an artificial immune network. The suggested Immune Network Algorithm based Multi-Agent System (INAMAS) provides intelligent mechanisms that capture disturbance-related knowledge explicitly and take advantage of previous successes and failures in dealing with disturbances through an adaptation of the reinforcement principle. To demonstrate the efficiency of the suggested control architecture, we assess its performance against two control strategies from literature, namely fixed-time control and a distributed adaptation of the Longest Queue First – Maximal Weight Matching (LQF-MWM) algorithm. Agents are developed using SPADE platform and used to control a network of signalized intersections simulated with VISSIM, a state-of-the-art traffic simulation software. The results show that INAMAS is able to handle different traffic scenarios with competitive performance (in terms of vehicle queue lengths and waiting times), and that it is particularly more successful than the other controllers in dealing with extreme situations involving blocked approaches and high traffic volumes. [ABSTRACT FROM AUTHOR]