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The body defense program is a remarkable self and non-self recognition system and normally reacts only against foreign invaders. Self-recognition and elimination of auto-reactive cells is a complex and continuous process of the body, which is monitored and controlled at different checkpoints. During the unresponsive state of tolerance, the lymphocytes remain alive but unresponsiveness and don't exert effective functions against an antigen particularly self-antigen. The defect or loss of this tolerance due to any etiological factor or agent results in self-reaction. Here we will discuss the updates in the function of the immune system and the mechanism of immune tolerance in normal and defective conditions, and how the system of self-defense assaults its body tissues.