Monstrous Crimes, Framing, and the Preventive State: The Moral Failure of Forensic Psychiatry
Monsters and predators frighten, entertain, and disgust us. The idea of a creature that is a volatile mixture of human and animal parts (the monster) triggers our visual and visceral imagination perhaps more than any other image. The fear of predation – literally, eating another’s flesh – disgusts and repels, but like rubberneckers who slow down to witness accidents, our voyeurism seems unconstrained by shame. The monster and the predator threaten us by threatening to rend the social fabric and bring about a state of nature in which, as Hobbes famously wrote, we are engaged in a war of all against all, and life is nasty, brutish and short. We demand that the government and its legal process protect us from the monsters and predators in our midst, which has resulted in a quest for security at the expense of the protection of the rights of citizens that runs parallel with the quest for protection from “terrorists,” as reflected in the epigram to this book. The referent of the “terrorist,” however, is often simply somebody who looks, acts, or talks in a way that is vaguely Middle-Eastern. Similarly, people who look, act, or talk like our vaguely sketched stereotype of what constitutes a sex offender, an image that has come to constitute a monstrous predator, trigger a panic as well (Lancaster 2011a, b).
The enemy within: endogenous retroelements and autoimmune disease
Inappropriate or chronic detection of self nucleic acids by the innate immune system underlies many human autoimmune diseases. We discuss here an unexpected source of endogenous immunostimulatory nucleic acids: the reverse-transcribed cDNA of endogenous retroelements. The interplay between innate immune sensing and clearance of retroelement cDNA has important implications for the understanding of immune responses to infectious retroviruses such as human immunodeficiency virus (HIV). Furthermore, the detection of cDNA by the innate immune system reveals an evolutionary tradeoff: selection for a vigorous, sensitive response to infectious retroviruses may predispose the inappropriate detection of endogenous retroelements. We propose that this tradeoff has placed unique constraints on the sensitivity of the DNA-activated antiviral response, with implications for the interactions of DNA viruses and retroviruses with their hosts. Finally, we discuss how better understanding of the intersection of retroelement biology and innate immunity can guide the way to novel therapies for specific autoimmune diseases.
TANK-binding kinase-1 delineates innate and adaptive immune responses to DNA vaccines
Successful vaccines contain not only protective antigen(s) but also an adjuvant component that triggers innate immune activation and is necessary for their optimal immunogenicity. In the case of DNA vaccines, this consists of plasmid DNA; however, the adjuvant element(s) as well as its intra- and inter-cellular innate immune signalling pathway(s) leading to the encoded antigen-specific T- and B-cell responses remain unclear. Here we demonstrate in vivo that TANK-binding kinase 1 (TBK1), a non-canonical IκB kinase, mediates the adjuvant effect of DNA vaccines and is essential for its immunogenicity in mice. Plasmid-DNA-activated, TBK1-dependent signalling and the resultant type-I interferon receptor-mediated signalling was required for induction of antigen-specific B and T cells, which occurred even in the absence of innate immune signalling through a well known CpG DNA sensor—Toll-like receptor 9 (TLR9) or Z-DNA binding protein 1 (ZBP1, also known as DAI, which was recently reported as a potential B-form DNA sensor). Moreover, bone-marrow-transfer experiments revealed that TBK1-mediated signalling in haematopoietic cells was critical for the induction of antigen-specific B and CD4+ T cells, whereas in non-haematopoietic cells TBK1 was required for CD8+ T-cell induction. These data suggest that TBK1 is a key signalling molecule for DNA-vaccine-induced immunogenicity, by differentially controlling DNA-activated innate immune signalling through haematopoietic and non-haematopoietic cells.