Weaknesses derived from Through-Silicon-Vias (TSV)-based physical configurations of three-dimension Multiprocessor System-on-Chip (3D-MPSoC) can be exploited by malicious software to attack the system. By means of vertical communication manipulation an attacker is able to modify, spy and even denial the TSV communication. In this paper we propose 3D-LeukoNoC, a flexible and efficient security architecture based on 3D-NoC communication structure which, as the biological immune system, is able to detect attacks, isolate sensitive vertical communication while guaranteeing the correct system behavior. We compare our approach with several 3D-protection proposals, including the simple extension of 2D security countermeasures. We show that our solution outperforms other approaches with respect to attack detection while decreasing cost and performance impact on the system.