Based on the biological immune mechanism, a design approach for the immune reconfigurable controller (IRC) is proposed. Using four units to imitate the immune system’s surveillance process, response process, memory mechanism, and self-learning process, respectively, the IRC is capable of actuator fault detection and fault-tolerant control for multi-input multioutput systems. Meanwhile, in order to further improve the control performance, an online optimization process with the multiobjective clonal selection algorithm is designed. To verify its effectiveness, the IRC is applied to the coagulation bath of polyacrylonitrile carbon fiber production line. Comparison experiments with conventional PID and reconfigurable model-based predictive controller control schemes are conducted. The simulation results demonstrate that the IRC can rapidly eliminate the fluctuation due to the actuator fault and guarantees the stability of the coagulation bath. In addition, the IRC has the ability of quick response to the same failure as well as unknown faults.