This essay, co-written by three art and technology humanities scholars from standpoints of autoimmune experience, takes up the longstanding critique of historical self/non-self models of the immune system to introduce a discussion about biopsychosocial and political affect in autoimmune experience of the 2020s. They argue that an ethos of tolerance and intolerance, long operative in biopolitical strategies of state power (Brown 2009), continues to factor into newer 21st century models of autoimmunity as biopsychosocial, ecological, distributed, and networked response. Drawing provisionally on the danger model (Matzinger 1994), which posits that immune responses are triggered by the perception of threat and not by the presence of “foreign” entities, the authors highlight the kernel of negative political affect in the signaling of danger. Drawing on the work of Silvan S. Tomkins, they describe, theorize, and interpret the role of sustained negative affect signaling, specifically (d)anger, distress, and disgust, in their own respective autoimmune experiences, which they describe as unfolding in achronic time (Freeman 2010, 126). It is proposed that closer scrutiny is needed for the negative affects that shape the infrastructure of (in)tolerance and care that gives life to autoimmune symptoms, diagnosis, and treatment experience in the 2020s, an era in which post-Covid autoimmune conditions unfold achronically in ongoing Covid-19 pandemic time.