 Pradeu formulated such criteria and proposed that the immune system plays the central role in determining what is included in the organism and what is not (Pradeu 2012). The differentiation is based on his continuity/discontinuity model, which depicts the immune system reacting to transient alterations in the pattern of antigen receptor interactions and tolerates long-lasting modifications (Pradeu, Jaeger, &amp; Vivier 2013; Pradeu &amp; Carosella 2006a: 241, 2006b). Such a mechanism is based on recognizing that autoimmunity is a normal function of immunity (Tauber 2015). Because host antigens do not evoke an immune response, a stable, “continuity” of immune interactions establishes an activation threshold that initiates an immune response only upon a rapid increase in antigenic load. The immune system thus distinguishes the stable state of tolerant recognition of tonic signals arising from normal physiological process in contrast to the appearance of novel antigens, for example, arising from pathogen invasion or tissue injury (Grossman and Paul 1992; Myers, Zikherman and Roose 2017; Pradeu 2012: 246; Grossman 2019). Thus the development of tolerance to frequently encountered antigens, commensals, tissue grafts and anastomosed animals results in the establishment of stable, integrated associations mediated by low-grade immune interactions (Pradeu and Carosella 2006a, 2006b; Pradeu 2012: 251–252). In this formulation, the immune system plays a central role in defining an individual by permitting beneficial physiological inclusion of heterologous components.