The present article has introduced a working model about the psychological immune system which was defined as a multidimensional but integrated unit of personal resilience resources or adaptive capacities that provide immunity against damage and stress giving in that way strong contributions to maintenance and facilitation of healthy individual functioning. One can say that human beings have capacities at biological and psychological level for surviving and struggling against difficulties in the process of adaptation. The tool of fight and defense at biological level is our biological immune system. At psychological level we have potential for the fight and for the defense to use unconscious and conscious tools, or as it was suggested by Epstein and Meier (1989) we have effective preconscious apparatus as well, which is the constructive thinking according to the authors. A differentiated functioning model of the unconscious fight and defense was worked out by Freud (1923/1961) and Anna Freud (1936) when they described the system of defense mechanism. Is there any special system at cognitive level which human beings can use as an effective tool for the fight, defense and effective/adaptive functioning in the process of adaptation to his/her social and physical environment? That question was addressed in the present writing. How one can define and identify that structure or unit within our psychological world which is essentially cognitively or consciously working and effectively guarantees a healthy and adaptive psychological functioning? Our suggestion is the Psychological Immune System which with its empirically validated 16 components roles as a protective apparatus strengthens invulnerability and raises the coping capacity of individuals. One question which is important to investigate is how the PIS takes part in the process of coping. As it was suggested in several writings of Lazarus (see Lazarus, 1993, for a rev.) coping is a central element of the cognitive appraisal process. The PIS focuses on the appraisal process. The psychological antibodies within the PIS are directly influential to the cognitive appraisal which acts in two modes, primary and secondary. As it was isolated empirical studies reported here, the PIS has three subsystems. The components of the PIS subsystems intimately relate to the different phases of the appraisal process. The immune traits of the Approach Believe Subsystem (Positive Thinking, Sense of Coherence, Sense of Control) have impact mainly on primary appraisal, while the personal resources of the Monitoring-Creating-Executing and the Self-Regulating Subsystems govern the secondary appraisal. The Monitoring-Creating-Executing subsystem directs the way of problem-focused or task-oriented coping, while the Self-Regulating Subsystem dominates over the emotion-focused behavior. As it was demonstrated in our studies the high level of the Creative Problem Solving, Social Creation Capacity and Self-efficacy highly correlated with the preference of the problem-focused way of coping. The Social-Monitoring and Social Mobilizing capacity components showed significant associations with the preference of coping by Seeking Social Support. The PIS through the secondary and primary appraisal mediates the effective and healthy way of coping with stress.