The adaptive immune system reacts against pathogenic nonself, whereas it normally remains tolerant to self. The initiation of an immune response requires a critical antigen(Ag)-stimulation and a critical number of Ag-specific T cells. Autoreactive T cells are not completely deleted by thymic selection and partially present in the periphery of healthy individuals that respond in certain physiological conditions. A number of experimental and theoretical models are based on the concept that structural differences discriminate self from nonself. In this article, we establish a mathematical model for immune activation in which self and nonself are not distinguished. The model considers the dynamic interplay of conventional T cells, regulatory T cells (Tregs) and IL-2 molecules and shows that the renewal rate ratio of resting Tregs to naive T cells as well as the proliferation rate of activated T cells determine the probability of immune stimulation. The actual initiation of an immune response, however, relies on the absolute renewal rate of naive T cells. This result suggests that thymic selection reduces the probability of autoimmunity by increasing the Ag-stimulation threshold of self reaction which is established by selection of a low number of low-avidity autoreactive T cells balanced with a proper number of Tregs. The stability analysis of the ordinary differential equation model reveals three different possible immune reactions depending on critical levels of Ag-stimulation: A subcritical stimulation, a threshold stimulation inducing a proper immune response, and an overcritical stimulation leading to chronic co-existence of Ag and immune activity. The model exhibits oscillatory solutions in the case of persistent but moderate Ag-stimulation, while the system returns to the homeostatic state upon Ag clearance. In this unifying concept, self and nonself appear as a result of shifted Ag-stimulation thresholds which delineate these three regimes of immune activation.

The invention of soft wearable assistive devices, known as exosuits, introduced a new aspect in assisting unimpaired subjects. In this study, we designed and developed an exosuit with compliant biarticular thigh actuators called BATEX. Unlike the conventional method of using rigid actuators in exosuits, the BATEX is made of serial elastic actuators (SEA) resembling artificial muscles. This bioinspired design is complemented by the novel control concept of using the ground reaction force to adjust the artificial muscles’ stiffness in the stance phase. By locking the motors in the swing phase, the SEAs will be simplified to passive biarticular springs, which is sufficient for leg swinging. The key concept in our design and control approach is to synthesize human locomotion to develop an assistive device instead of copying human motor control outputs. Analyzing human walking assistance using experiment-based OpenSim simulations demonstrates the advantages of the proposed design and control of BATEX, such as 9.4% reduction in metabolic cost during normal walking condition. This metabolic reduction increases to 10.4% when the subjects carry a 38 kg load. The adaptability of our proposed model-based control to such an unknown condition outperforms the assistance level of the model-free optimal controller. Moreover, increasing the assistive system’s efficiency by adjusting the actuator compliance with the force feedback supports our previous findings on the LOPES II exoskeleton.