I propose a T‐cell receptor (TcR)‐based mechanism by which immunity mediates both “genetic self” and “microbial self” thereby, connecting microbiome disease with autoimmunity. The hypothesis is based on simple principles. First, TcR are selected to avoid strong cross‐reactivity with “self,” resulting in selection for a TcR repertoire mimicking “genetic self.” Second, evolution has selected for a “microbial self” that mimics “genetic self” so as to share tolerance. In consequence, our TcR repertoire also mimics microbiome antigenicity, providing a novel mechanism (...) for modulating tolerance to it. Also, the microbiome mimics the TcR repertoire, acting as a secondary immune system. I call this TcR‐microbiome mimicry “holoimmunity” to denote immune tolerance to the “holobiont self.” Logically, microbiome‐host mimicry means that autoimmunity directed at host antigens will also attack components of the microbiome, and conversely, an immunological attack on the microbiome may cross‐react with host antigens producing “holoautoimmunity.”. (shrink)

I argue that a distinction between three autoimmunities is implied in Derrida’s _Rogues_. These are the autoimmunities of democracy as a regime of power, of democracy to come and of sovereignty. I extrapolate the relations between three different autoimmunities using the figure of the internal enemy in order to argue for an agonistic conception of democracy.

Traditionally, autoimmune disease has been considered to be a case of false recognition; the immune system mistakenly identifies 'self' tissues as foreign, attacking them thus causing damage and malady. Accordingly, the history of autoimmunity is usually told as part ot the history of immunology, that is, of theories and experiments relating to the ability of the immune system to discriminate between self and nonself. This paper challenges this view, claiming that the emergence of the notion of autoimmunity in (...) the 1950s must be considered as part of a long develolpment in thought about pathology throughout the twentieth century, namely the conceptualisaiton of disease as a reactive and self-destructive process. During the first part of the twentieth century this notion became one of the cornerstones of pathology and was increasingly employed for the explanation of the non-infections, slow-burning diseases. Thus, the category of chronic disease had been defined anew, now encompassing all those diseases characterised by a persistent inflammatory process. Inflammation, in turn, was conceived as double-eged physiological mechanism, which was usually the direct mediator of damage, of the essence of disease. The paper also shows how this kind of analysis could emable a unified historical discussion of autoimmunity and allergy, hitherto considered to have distinct conceptual origins. (shrink)

Introduction. Toward a hermeneutics of skepticism -- Montaignean meditations -- Ideology, critique, and the event of literature -- Irony, power, and the death drive -- Queering difference, or the feminine logic of the "non-all" -- Immunizing ontology : the speculative turn -- Conclusion. Desire of the theorist.

Our paper is a comparative analysis of Alexander Dugin's The Fourth Way and Karl Popper's The Open Society. Both works of the two thinkers are viewed as completely concrete (and real) conceptual frameworks, offering two radically different models of perception of the world, the individual and community relations, of the international relations. Our analysis takes into consideration both the internal, that is the “intimate enemies of democracy”, and the new (old) enemies of the open society that “relapse” through the Fourth (...) Way. Our theoretical research is focused on the parallel between the negative starting premises for the functioning of the Open Society – historicism, utopian social engineering, collectivism and chieftainism – studied in relation to the same principles, which, respectively, are the foundation of the Fourth Political Theory. The article also considers another important problem: the thesis, that the internal, autoimmune diseases of the Open Society, are in fact the preconditions, on which the doctrines of its external opponents are based. (shrink)

Shortly before his death in 2004, Jacques Derrida provocatively suggested that the greatest problem confronting contemporary democracy is that ‘the alternative to democracy can always be represented as a democratic alternative ’. This article analyses the manner in which certain manifestly anti-democratic practices, like terror and torture, come to be taken up in defense of democracies as a result of what Derrida calls democracy’s ‘autoimmune’ tendencies.

This article suggests that the historical figuration of Islam as well as the discourse of secularization has played a fundamental role in the constitution of Islam’s externality to Europe. The historical figuration of Islam as Europe’s enemy is haunting Europe. The European secularist anxiety today, which insists on the separation between the domains of the private and the public needs to be understood against the backdrop of this history. If Islam’s inability to separate the religious and the political was historically (...) the dominant motif through which Islam was registered as the arch-enemy, the post-secular, post-Enlightenment period registers Islam as an enemy through a cultural gesture. Derrida’s understanding of spectrality and the concept autoimmunity are deployed to suggest that Islam as a specter haunting Europe undermines the sovereign constitution of a self-identical Europe, but this haunting needs to be seen as Europe’s chance for a self-destructive conservation of Europe. European identity has to be rethought and renewed differently and this rethinking requires that we attend to the present as well as the past and future of Europe, which requires the opening of Europe to otherness and responsibility to the other. Such a rethinking of Europe’s history necessitates thinking about colonialism as well the living embodiments of this colonial legacy today, which are the immigrants. (shrink)

I begin by examining the logic of autoimmunity as characterized by Jacques Derrida, ‘that strange behaviour where a living being, in quasi-suicidal fashion, ‘‘itself’’ works to destroy its own protection, to immunize itself against its own immunity’ (Borradori, 2003: 94). According to Derrida, religion, democracy, terrorism and recent responses to the trauma of terrorism can be understood in terms of this logic. Responses to terrorism are ‘autoimmune’ and increase the trauma of terrorism as well as risking democratic values. I (...) argue that the risks of autoimmunity can be negotiated in better ways if we see how autoimmunity relates to another important Derridean concept, hospitality. (shrink)

Political activists can cheer when Jacques Derrida says that his idea of “democracy to come” is “a call for militant and interminable political critique.” Our acclamations grow louder when he adds that this idea is “a weapon aimed at the enemies of democracy.” He identifies these “enemies” as people who use the discourse of democracy as an “obscene alibi” for “tolerating the plight” of people “deprived of bread and water” and “equality or freedom.”1 He accuses the United States of committing (...) this sort of hypocrisy when it denounces other states for practicing the very roguery in which it indulges.2We can also praise Derrida for what he offers us as well as rejects. He comments that there is a need for a “European... (shrink)

This essay explores the treatment of violence in Derrida's ethico-political work, stressing the underlying continuity of Derrida's thinking of politics, from his first reading of Levinas to one of the last notions he developed, autoimmunity. Haddad analyzes the use to which the idea of a “lesser violence” has been put, arguing that it is incompatible with Derrida's other claims.

The aim of this article is to read Rogues, in order to show that Derrida is neither a philosopher of democracy nor a critic of sovereignty, but rather a thinker of democratic sovereignty. Taking my cue from his Aporias, I argue that democratic sovereignty is aporetically in excess over itself, for it is based on articulating the path through the im-possible passage from the unconditional injunction of the ‘promise’ to the exigency of sovereignty. That is why it can neither be (...) absorbed into the conditions of any existing democracy nor abstracted into any pure identity of sovereignty. Political trends today fail in enduring the aprioricity of aporia, as neoliberals valorize the posited conditions of existing democracy and populists the objective pregivenness of the ‘people’. (shrink)

Here we discuss the hypothesis that the RNA components of the Ro ribonucleoproteins (RNPs), the Y RNAs, can be processed into microRNAs (miRNAs). Although Ro RNPs, whose main protein components Ro60 and La are targeted by the immune system in several autoimmune diseases, were discovered many years ago, their function is still poorly understood. Indeed, recent data show that miRNA-sized small RNAs can be generated from Y RNAs. This hypothesis leads also to a model in which Ro60 acts as a (...) modulator in the Y RNA-derived miRNA biogenesis pathway. The implications of these Y RNA-derived miRNAs, which may be specifically produced under pathological circumstances such as in autoimmunity or during viral infections, for the enigmatic function of Ro RNPs are discussed. (shrink)

A pathogenic connection between autoreactive T cells, fungal infection, and carcinogenesis has been demonstrated in studies of human autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy as well as in a mouse model in which kinase-dead Ikkα knock-in mice develop impaired central tolerance, autoreactive T cell–mediated autoimmunity, chronic fungal infection, and esophageal squamous cell carcinoma, which recapitulates APECED. IκB kinase α is one subunit of the IKK complex required for NF-κB activation. IKK/NF-κB is essential for central tolerance establishment by regulating the development of medullary (...) thymic epithelial cells that facilitate the deletion of autoreactive T cells in the thymus. In this review, we extensively discuss the pathogenic roles of inborn errors in the IKK/NF-κB loci in the phenotypically related diseases APECED, immune deficiency syndrome, and severe combined immunodeficiency; differentiate how IKK/NF-κB components, through mTEC, T cells/leukocytes, or epithelial cells, contribute to the pathogenesis of infectious diseases, autoimmunity, and cancer; and highlight the medical significance of IKK/NF-κB in these diseases. IKK/NF-κB regulates the expression of many genes that encode proteins involved in many crucial biological functions, such as immunity, tissue homeostasis, and fungal/bacterial/viral infections. Also, IKKα plays anti-tumor activities in many organs independently of NF-κB pathways. Thus, an inborn error in one of these gene loci can cause severe human diseases through these complicated mechanisms. (shrink)

Systemic autoimmune diseases are characterized by the production of antibodies against a broad range of self-antigens. Recent evidence indicates that the majority of these autoantigens are modified in various ways during cell death. This has led to the hypothesis that the primary immune response in the development of autoimmunity is directed to components of the dying cell. In this article, we summarize data on the modification of autoantigens during cell death and the possible consequences of this for autoimmunity. (...) BioEssays 22:627–636, 2000. © 2000 John Wiley & Sons, Inc. (shrink)

The pregnancy compensation hypothesis provides a mechanistic explanation for the evolution of sex differences in immune system functioning, the excess of women experiencing autoimmune disease, and why this is observed only in industrialized nations; none of which can be explained by the staying alive theory, as proposed by the authors of the target article.

The molecular components of complement are a major part of the armoury of the mammalian immune system, being required for the lysis of antibody‐targeted cells. Several of the complement proteins are known to be encoded by genes within the major histocompatibility complex (MHC). Molecular analysis of these genes is providing new information on the basis of complement action and the possible roles of this system in autoimmune disease.

The nonobese diabetic (NOD) mouse spontaneously develops an autoimmune diabetes that shares many immunogenetic features with human insulin-dependent diabetes mellitus (IDDM), type 1 diabetes. The mononuclear cell infiltrates in the islet, which results in the development of insulitis (a prerequisite step for the development of diabetes) are primarily composed of T cells. It is now well accepted that these T cells play important roles in initiating and propagating an autoimmune process, which in turn destroys insulin-producing islet β cells in the (...) pancreas. T cells are subdivided into CD4+ helper T cells and CD8+ cytotoxic T cells. CD4+ T cells are further subdivided into Th1 and Th2 cells based on profiles of cytokine production, and these two T-cell populations counterregulate each other. Because many autoimmune diseases are Th1 T-cell mediated, current studies have focused on manipulating the Th1/Th2 imbalance to suppress the autoimmune process in the NOD model. Furthermore, the incidence of disease is much higher in females than that in males, suggesting an involvement of sex-steroid hormones in the development of diabetes. Understanding insights of the mechanism of immune-mediated islet cell destruction and the interaction between the immune and the neuroendocrine system may, therefore, provide new therapeutic means of preventing this chronic debilitating disease. BioEssays 20:750–757, 1998. © 1998 John Wiley & Sons, Inc. (shrink)

During the final decade of his life, Jacques Derrida came to use the trope of autoimmunity with greater and greater frequency. Indeed it today appears that autoimmunity was to have been the last iteration of what for more than forty years Derrida called deconstruction. This essay looks at the consequences of this terminological shift for our understanding not only of Derrida's final works (such as Rogues) but of his entire corpus. By taking up a term from the biological (...) sciences that describes the process by which an organism turns in quasi-suicidal fashion against its own self-protection, Derrida was able to rethink the very notion of life otherwise and demonstrate the way in which every sovereign identity, from the self to the nation-state to, most provocatively, God, is open to a process that both threatens to destroy it and gives it its only chance of living on. (shrink)

This essay uses Derrida's concept of autoimmunity to critique Homeland, a television show that deals with an American prisoner of war who has been ‘turned’ into an operative for an al Queda-like movement. Autoimmunity is critical to thinking the ways in which the existence of a turned POW within the state, who belongs visibly to the state, presents a particularly heteronomic challenge to how the distinction between Self and Other operates. This Self who has taken up the cause (...) of the Other presents, this essay argues, an infinitely greater threat to the state precisely because it cannot be identified as Other, precisely because bears no ostensible traces of the Other. (shrink)

This article analyses the biochemical object of tnf inhibitors from the perspective of living with an autoimmune disease. The author tries to tease out how the concept of immune inhibition is used in tandem with the biochemical object of tnf inhibitors to dominate in defining and narrating what health and disease, normal and pathological, cure and healing can mean in the context of autoimmune bodies. Specifically, and within the ‘pathological’ framework of autoimmune diseases, the pharmacological treatment of tnf inhibition is (...) designed to suppress the ‘overly’ active immune system, thus acting as a negative or suppressing biochemical agent aimed at putting the ‘malfunctioning’ immune system back in balance. As can be seen in the current conjuncture, tnf inhibitors officially —and governmentally— place those taking them in a risk group, as they 'lower' their overall bodily immunity and make them more vulnerable to infectious diseases, while stabilizing their patho-logical, ‘over’-immune uninhibited condition. Part personal narrative of being diagnosed with an autoimmune condition, part speculative autoimmune theory inspired by such a diagnosis, the article ultimately calls for a different form of embodiment that is neither negative nor affirmative, and yet is resistant even to itself. (shrink)

Certain steroids can react with proteins to form stable, covalent addition products. 16α‐hydroxyestrone and the glucocorticoids, for example, contain ketol moieties which permit them to react non‐enzymatically with proteins by forming Schiffbase rearrangement products with lysine residues. The oral contraceptive agent, 17α‐ethinylestradiol, can add to proteins after being enzymatically activated by microsomal oxidation. Elevated plasma levels of these steroids result in an increased amount of protein modification in vivo. Recent investigations have linked the occurrence of steroid‐modified proteins with pathological sequelae (...) associated with high steroid levels. (shrink)

(2009). “Twenty Paragraphs of Written Instructions”. Angelaki: Vol. 14, shadows of cruelty sadism, masochism and the philosophical muse – part one, pp. 59-68.

Severe COVID‐19 is often accompanied by coagulopathies such as thrombocytopenia and abnormal clotting. Rarely, such complications follow SARS‐CoV‐2 vaccination. The cause of these coagulopathies is unknown. It is hypothesized that coagulopathies accompanying SARS‐CoV‐2 infections and vaccinations result from bacterial co‐infections that synergize with virus‐induced autoimmunity due to antigenic mimicry of blood proteins by both bacterial and viral antigens. Coagulopathies occur mainly in severe COVID‐19 characterized by bacterial co‐infections with Streptococci, Staphylococci, Klebsiella, Escherichia coli, and Acinetobacter baumannii. These bacteria express (...) unusually large numbers of antigens mimicking human blood antigens, as do both SARS‐CoV‐2 and adenoviruses. Bacteria mimic cardiolipin, prothrombin, albumin, and platelet factor 4 (PF4). SARS‐CoV‐2 mimics complement factors, Rh antigens, platelet phosphodiesterases, Factors IX and X, von Willebrand Factor (VWF), and VWF protease ADAMTS13. Adenoviruses mimic prothrombin and platelet factor 4. Bacterial prophylaxis, avoidance of vaccinating bacterially infected individuals, and antigen deletion for vaccines may reduce coagulopathy risk. Also see the video abstract here: https://youtu.be/zWDOsghrPg8. (shrink)

Few topics in contemporary science hold the wide interest commanded by immunology, so this graceful and timely account of the development of this science is a welcomed addition to the literature. Succinct, well-written, and informed, Intolerant Bodies narrates the history of immunology through the lens of autoimmune disease. In what the authors call “a biography” , they have focused on four central illnesses: multiple sclerosis, systemic lupus erythematosus, rheumatoid arthritis, and type 1 diabetes mellitus. However, the story told here extends (...) far beyond the topic of “attack against self” to provide perhaps the best overview of immunity available for the general reader. The specialist will also appreciate the rich anecdotal material and benefit from the historical insights scattered throughout the text. So the book is, in fact, more than a history of autoimmunity and offers a compact history for those who need not consult more comprehensive accounts (e .. (shrink)

Stuttering is one of the most well-known speech disorders, but the underlying neurological mechanisms are debated. In addition to genetic factors there are also major non-genetic contributions. It is here proposed that infection with group A beta-hemolytic streptococcus (GAS) was a major underlying cause of stuttering until the mid 1900s, when penicillin was introduced for the treatment of streptococcal infections about 1946. The main mechanism proposed is an autoimmune reaction from tonsillitis, targeting specific molecules, for example within the basal ganglia. (...) It is here also proposed that GAS infections may have continued to cause stuttering to some extent, to the present date, though more rarely. If so, early diagnosis of such cases would be of importance. Childhood cases with sudden onset of stuttering after throat infection may be particularly important to assess for possible GAS infection. The support for this hypothesis primarily comes from three lines of argument. First, medical record data from the 1930s strongly indicates that there was one type of medical event in particular that preceded the onset of childhood stuttering with unexpected frequency: diseases related to GAS throat infections. In particular, this included tonsillitis and scarlet fever, but also rheumatic fever. Rheumatic fever is a childhood autoimmune sequela of GAS infection, which was a relatively widespread medical problem until the early 1960s. Secondly, available reports of changes of the childhood prevalence of stuttering indicates striking parallels between stuttering and the incidence of rheumatic fever, with (1) decline from the early 1900s, (2) marked decline from the introduction of penicillin about 1946, and (3) reaching a more stable level in the 1960s. The correlations between the data for stuttering and for rheumatic fever after introduction of penicillin are very high, at about 0.95. Thirdly, there are established biological mechanisms linking GAS tonsillitis to immunological effects on the brain. In addition, a small number of more recent case reports have provided further support for the hypothesis linking stuttering to GAS infection. Overall, it is proposed that the available data provides strong evidence for the hypothesis that GAS infection was a major cause of stuttering until the mid 1900s. (shrink)

The presence of fetal cells has been associated with both positive and negative effects on maternal health. These paradoxical effects may be due to the fact that maternal and offspring fitness interests are aligned in certain domains and conflicting in others, which may have led to the evolution of fetal microchimeric phenotypes that can manipulate maternal tissues. We use cooperation and conflict theory to generate testable predictions about domains in which fetal microchimerism may enhance maternal health and those in which (...) it may be detrimental. This framework suggests that fetal cells may function both to contribute to maternal somatic maintenance (e.g. wound healing) and to manipulate maternal physiology to enhance resource transmission to offspring (e.g. enhancing milk production). In this review, we use an evolutionary framework to make testable predictions about the role of fetal microchimerism in lactation, thyroid function, autoimmune disease, cancer and maternal emotional, and psychological health.Also watch the Video Abstract. (shrink)

Cosmopolitanism has ancient roots in the West and the East. A view that appeals to a quasi‐transcendental basis for cosmopolitan democracy can seem unacceptably ephemeral; yet a conditional view may amount to no more than a worldwide modus vivendi despite its claims to moral bonds of unity. This chapter shows how Jacques Derrida's notion of democracy or cosmopolitanism confronts this issue. Contemporary Marxism provides one of the most systematic characterizations and criticisms of the modern form of globalization. Derrida says that (...) he agrees with the spirit of Marxism, particularly its openness to transformative self‐critique and even more to “a certain emancipatory and messianic affirmation... or promise”. The notion of a “call” plays a pivotal role in Derrida's analysis of democracy and many of his other ideas. Derrida appeals to the notion of autoimmunity to formalize the sense in which he says democracy to come is “impossible.”. (shrink)

This essay attempts to lay out the three principal theses of Jacques Derrida’s 1994-1995 “Faith and Knowledge,‘ Derrida’s most sustained but also most challenging work on the nature of religion and the relationship between religion and science. After demonstrating through these three theses that religion and science not only share a common source-or have a common genesis-but are in what Derrida calls an autoimmune relationship to one another, the essay puts these theses to the test by reading a brief passage (...) near the middle of the essay where Derrida recounts the genesis of “Faith and Knowledge‘ itself Derrida’s seemingly anecdotal recounting of this genesis is thus shown to reflect the three theses of “Faith and Knowledge,‘ the way in which, in a word, the breath of creation, or the miracle of religion, is always doubled, supplemented, and thus contaminated by the machine of science and tele-technology. (shrink)

Building from the works of Jacques Derrida, this article explores health anxiety’s aporetic relationship with medicine through a deconstructive approach. I argue that attention to Derrida’s writings (and in particular, his readings of pharmakon and autoimmunity) may prove useful in explaining the cyclical character of health anxiety and its ambivalent response to medical reassurance. What’s more, I demonstrate how structuralist interpretations of health anxiety as a signifier without referent prove insufficient within a Derridean account. Such a reading emphasizes the (...) need for interdisciplinary medical humanities as well as critical reflections on the possible limitations of Western medical semiotics. (shrink)

Chemokines (chemotactic cytokines) drive and direct leukocyte traffic. New evidence suggests that the unusual CCR6/CCL20 chemokine receptor/ligand axis provides key homing signals for recently identified cells of the adaptive immune system, recruiting both pro‐inflammatory and suppressive T cell subsets. Thus CCR6 and CCL20 have been recently implicated in various human pathologies, particularly in autoimmune disease. These studies have revealed that targeting CCR6/CCL20 can enhance or inhibit autoimmune disease depending on the cellular basis of pathogenesis and the cell subtype most affected (...) through different CCR6/CCL20 manipulations. Here, we discuss the significance of this chemokine receptor/ligand axis in immune and inflammatory functions, consider the potential for targeting CCR6/CCL20 in human autoimmunity and propose that the shared evolutionary origins of pro‐inflammatory and regulatory T cells may contribute to the reason why both immune activation and regulation might be controlled through the same chemokine pathway. (shrink)

In an instant classic paper ; 2002: 179–182) biologist Yuri Lazebnik deplores the poor effectiveness of the approach adopted by biologists to understand and “fix” biological systems. Lazebnik suggests that to remedy this state of things biologist should take inspiration from the approach used by engineers to design, understand, and troubleshoot technological systems. In the present paper I substantiate Lazebnik’s analysis by concretely showing how to apply the engineering approach to biological problems. I use an actual example of electronic circuit (...) troubleshooting to ground the thesis that, in engineering, the crucial phases of any non-trivial troubleshooting process are aimed at generating a mechanistic explanation of the functioning of the system, which makes extensive recourse to problem-driven qualitative reasoning possibly based on cognitive artifacts applied to systems that are known to have been designed for function. To show how to translate these findings into biological practice I consider a concrete example of biological model building and “troubleshooting”, aimed at the identification of a “fix” for the human immune system in presence of progressing cancer, autoimmune disease, and transplant rejection. The result is a novel immune system model—the danger model with regulatory cells— and new, original hypotheses concerning the development, prophylaxis, and therapy of these unwanted biological processes. Based on the manifest efficacy of the proposed approach, I suggest a refocusing of the activity of theoretical biologists along the engineering-inspired lines illustrated in the paper. (shrink)