 Wide use of the self/nonself distinction in different clinical and research traditions (provided by the relaxed and varied meanings associated with its use) has established such discrimination as the governing construct of the science (e.g., Howes 2010; Hoffman 2012; Cohn 2015). Indeed, the “immune self” has served as immunology’s foundational concept to order immune theorizing for the past 70 years (Burnet and Fenner 1949; Tauber 1994). However, despite the paradigm’s established standing, definition of immune identity has proven elusive. As discussed above (section 2.1), because of fluctuations of immune activity over the lifespan of the organism, conceptualizing and modeling active tolerance have yet to yield criteria for defining stable identity (Bilate and LaFaille 2012). Moreover, a consensus definition of selfhood has remained elusive inasmuch as different investigative frameworks promote differing characteristics of immune identity based on their respective structural and functional criteria (Matzinger 1994). Critics have therefore questioned the immune self’s standing and utility (e.g., Matzinger 1994; Tauber 2000; Pradeu 2012). The latter position argues that the “self” might be better regarded as only a metaphor for a “figure” outlined by the immune system’s silence, i.e., its non-reactivity. Such a functionally flexible definition has been resisted. Defenders argue that the notion of stabilized discrimination correctly depicts the immune system’s organizing functions (which converge on defending a well-demarcated organism), and that efforts to eliminate or modify this metaphor are misguided attempts to “police” borders between science and culture (Anderson 2014; Hoffman 2012). Drawing from the philosophical canon, Howes referred to Hume to argue that realism about self (immune or otherwise) can be saved despite the dependency of context and the ever-changing character of the postulated ego (Howes 1998). She suggested that the efforts to deny the reality of the self are based on its non-substantial character and thus reflects entrenched substantialist assumptions. She proposed that a middle ground exists between substantial self and no-self by adopting a processual, understanding of selfhood (Howes 1999).