 Jerne’s provocative hypothesis, although elegant in conception and effective in inspiring new avenues of research, did not withstand critical evaluation (Eichmann 2008; Vaz 2011a, 2011b). Despite confirming the presence of idiotypic antibodies (i.e., mutually interacting immunoglobulin molecules), their role and overall contribution to immune functions remained uncertain. Furthermore, the idea of autonomy and closure contradicted empirical evidence (Hershberg and Efroni 2001; Coutinho 2003). However, notions of cognition without agency remained plausible. Pradeu and colleagues similarly proposed that the state of the immune system is structured by inter-connected elements, where activation results from perturbations of the stable linkages of the resting state (Pradeu and Carosella 2006a, 2006b; Pradeu, Jaeger, and Vivier 2013). The original “network” theory focused upon the inter-actions of the immune system’s constituents, (Jerne 1974), while the “continuity” theory employs an architecture of antigenic-immune interactions (Pradeu 2012, 2018; Grossman and Paul 2015). When the immune system is regarded from this “connected” perspective, tolerance is the result of a stable continuity of interactions between an antigen and its receptors. Thus, integrated states are quiescent and disrupted ones, whether “foreign” or endogenous, generate immune activation by breaking stabilized associations.