Many innate immune response proteins recognize foreign nucleic acids from invading pathogens to initiate antiviral signaling. These proteins mostly rely on structural characteristics of the nucleic acids rather than their specific sequences to distinguish self and nonself. One feature utilized by RNA sensors is the extended stretch of double‐stranded RNA (dsRNA) base pairs. However, the criteria for recognizing nonself dsRNAs are rather lenient, and hairpin structure of self‐RNAs can also trigger an immune response. Consequently, aberrant activation (...) of RNA sensors has been reported in numerous human diseases. Yet, in most cases, the activating antigens remain unknown. Recent studies have developed sequencing techniques tailored to specifically capture dsRNAs and identified that various noncoding elements in the nuclear and the mitochondrial genome can generate dsRNAs. Here, the identity of endogenous dsRNAs, their recognition by dsRNA sensors, and their implications in the pathogenesis of human diseases ranging from inflammatory to degenerative are presented. (shrink)

Immunology and its philosophy are a primary source for thinking about biological individuality. Through its discriminatory function, the immune system is believed to delineate organism and environment within one generation, thus defining the physiological individual. Based on the paradigmatic instantiations of immune systems, immune interactions and, thus, the physiological individual are believed to last only for one generation. However, in recent years, transgenerationally persisting immune responses have been reported in several phyla, but the consequences for physiological (...) individuality have not yet been explored. In this article, I will introduce an invertebrate immune system that is RNA-based and operates through a heritable silencing/licensing paradigm. I will discuss how such a perspective on immune systems can illuminate our conceptions of individuality. I will particularly introduce an account of immunological individuality that is not restricted to one generation. (shrink)

In the postgenomic era, interactions between organism and environment are central in disciplines such as epigenetics, medical physiology, and immunology. Particularly in the more "applied" medical fields, an emphasis lies on interactions of the organism with other organisms, that is, other living things. There is, however, a growing amount of research investigating the impact of abiotic triggers on the immune system. While the distinction between biota and abiota features heavily in other contexts, its status is not explicit within immunology. (...) Do immunologists distinguish living from nonliving triggers? In this article, I will carve out whether and in which ways the biotic/abiotic distinction operates in immunology. I will look into responses to biotic and abiotic stressors in plant and invertebrate model species and ask how and why they are conceptually separated. I will trace the reasons by investigating the disciplinary situatedness of immune phenomena and the import of vertebrate immunology when conceptualizing immune responses in other model organisms. I will then investigate how the convergence of biotic and abiotic stress responses in plants and invertebrates adds to the recent philosophical programs advocating an ecological perspective on immune systems. (shrink)

The intensity and prevalence of viral infections are typically higher in males, whereas disease outcome can be worse for females. Females mount higher innate and adaptive immune responses than males, which can result in faster clearance of viruses, but also contributes to increased development of immunopathology. In response to viral vaccines, females mount higher antibody responses and experience more adverse reactions than males. The efficacy of antiviral drugs at reducing viral load differs between the sexes, and the adverse (...) reactions to antiviral drugs are typically greater in females than males. Several variables should be considered when evaluating male/female differences in responses to viral infection and treatment: these include hormones, genes, and gender‐specific factors related to access to, and compliance with, treatment. Knowledge that the sexes differ in their responses to viruses and to treatments for viral diseases should influence the recommended course of action differently for males and females.Editor's suggested further reading in BioEssays X‐chromosome‐located microRNAs in immunity: Might they explain male/female differences Abstract. (shrink)

Physiologically accurate mouse models of cancer are critical in the pre‐clinical development of novel cancer therapies. However, current standardized animal‐housing temperatures elicit chronic cold‐associated stress in mice, which is further increased in the presence of tumor. This cold‐stress significantly impacts experimental outcomes. Data from our lab and others suggest standard housing fundamentally alters murine physiology, and this can produce altered immune baselines in tumor and other disease models. Researchers may thus underestimate the efficacy of therapies that are benefitted by (...) immune responses. A potential mediator, norepinephrine, also underlies stress pathways common in mice and humans. Therefore, research into mechanisms connecting cold‐stress and norepinephrine signaling with immune depression in mice could highlight new combination therapies for humans to simultaneously target stress while stimulating anti‐tumor immunity. (shrink)

Ascorbic acid is a redox regulator in many physiological processes. Besides its antioxidant activity, many intriguing functions of ascorbic acid in the expression of immunoregulatory genes have been suggested. Ascorbic acid acts as a co‐factor for the Fe+2‐containing α‐ketoglutarate‐dependent Jumonji‐C domain‐containing histone demethylases (JHDM) and Ten eleven translocation (TET) methylcytosine dioxygenasemediated epigenetic modulation. By influencing JHDM and TET, ascorbic acid facilitates the differentiation of double negative (CD4−CD8−) T cells to double positive (CD4+CD8+) T cells and of T‐helper cells to different (...) effector subsets. Ascorbic acid modulates plasma cell differentiation and promotes early differentiation of hematopoietic stem cells (HSCs) to NK cells. These findings indicate that ascorbic acid plays a significant role in regulating both innate and adaptive immune cells, opening up new research areas in Immunonutrition. Being a water‐soluble vitamin and a safe micro‐nutrient, ascorbic acid can be used as an adjunct therapy for many disorders of the immune system. (shrink)

By integrating the entire body of research in human sexual dynamics, immune responses, and sociocultural behavior, we can conclude that the mass hysteria our society is currently experiencing originates in our evolved psychological adaptations to pandemic conditions [i]. A lack of hormonal balance [ii], due to a collapse in testosterone levels, may cause a disproportionate immune response that leads to the destruction of our cherished sociopolitical institutions—the very institutions that are design to protect human liberty and prosperity. (...) What is playing out at a societal level is similar to an excessive immune response that causes the body to attack itself: decreased testosterone causing the kind of auto-immune response that is more prevalent in females. [i] Barzilai, R.. Low Solar Activity, Winter Flu Conditions, Pandemics and Sex Wars: A Holistic View of Human Evolution. Science & Philosophy, 8. Doi: 10.23756/sp.v8i1.514 [ii] Barzilai, R.. Solar cycles, light, sex hormones and the life cycles of civilization: Toward integrated chronobiology. Science & Philosophy, 7. doi: 10.23756/sp.v7i2.483. (shrink)

There is a steadily growing literature on the role of the immune system in psychiatric disorders. So far, these advances have largely taken the form of correlations between specific aspects of inflammation (e.g. blood plasma levels of inflammatory markers, genetic mutations in immune pathways, viral or bacterial infection) with the development of neuropsychiatric conditions such as autism, bipolar disorder, schizophrenia and depression. A fundamental question remains open: why are psychiatric disorders and immune responses intertwined? To address this (...) would require a step back from a historical mind–body dualism that has created such a dichotomy. We propose three contributions of active inference when addressing this question: translation, unification, and simulation. To illustrate these contributions, we consider the following questions. Is there an immunological analogue of sensory attenuation? Is there a common generative model that the brain and immune system jointly optimise? Can the immune response and psychiatric illness both be explained in terms of self-organising systems responding to threatening stimuli in their external environment, whether those stimuli happen to be pathogens, predators, or people? Does false inference at an immunological level alter the message passing at a psychological level (or vice versa) through a principled exchange between the two systems? (shrink)

Recently, we found that the Pseudomonas aeruginosa type II secreted protease IV functions as a unique Arabidopsis innate immunity elicitor. The protease IV‐activated pathway involves G protein signaling and raises the question of how protease elicitation leads to the activation of G protein‐mediated signaling, because plants do not appear to have metazoan‐like G protein‐coupled receptors. Importantly, our data suggest that Arabidopsis has evolved a mechanism to detect the proteolytic activity of a pathogen‐encoded protease, supporting the host‐pathogen arms race model. In (...) the case of opportunistic multi‐host pathogens like P. aeruginosa, however, it is not plausible that P. aeruginosa is simultaneously co‐evolving in a gene‐for‐gene manner with all of its potential hosts, which include plants, nematodes, insects, and mammals. This prompts us to ask what is the driving force for co‐evolution of defense response in Arabidopsis and pathogenesis of P. aeruginosa, which might not have been subject to iterative cycles of evolutionary selections. (shrink)

Coordination of immune responses in the gut is a complex task. In order to fight pathogens and maintain a defined population of commensal microbes, the mucosal immune system has to coordinate information from the external (luminal) and internal (abluminal) environment and respond accordingly. Dendritic cells (DCs) are crucial cell types involved in this process as they integrate these signals and direct immunogenic or tolerogenic responses. Here, we review how various functions of DCs depend on microbial stimuli and how (...) these stimuli influence the course of immune activation. (shrink)

The question as to why some hosts can eradicate their tumors while others succumb to tumor‐progression remains unanswered. Here, a provocative concept is proposed that intrinsic differences in the T cell receptor (TCR) repertoire of individuals may influence the outcome of anti‐tumor immunity by affecting the frequency and/or variety of tumor‐reactive CD8 and/or CD4 tumor‐infiltrating lymphocytes. This idea implicates that the TCR repertoire in a given patient might not provide sufficiently different TCR clones that can recognize tumor antigens, namely, “a (...) hole in the TCR repertoire” might exist. This idea may provide a novel perspective to further dissect the mechanisms underlying heterogeneous anti‐tumor immune responses in different hosts. Besides tumor‐intrinsic heterogeneity and host microbiome, the various factors that may constantly shape the dynamic TCR repertoire are also discussed. Elucidating mechanistic differences in different individuals’ immune systems will allow to better harness immune system to design new personalized cancer immunotherapy. (shrink)

Cytotoxic lymphocytes play a central role in immune inflammatory responses against tumour cells, viruses and cells transplanted or infected with intracellular bacteria. The pivotal importance of lymphocytes in each of these immune responses has justified our continued interest in their cytotoxic function. Recent studies of cytotoxic lymphocytes have involved the characterisation of recognition structures on cytotoxic lymphocytes and the definition of two mechanisms of cytotoxicity. In contrast to normal cell death, which occurs during embryonic development and the formation (...) and death of hematopoietic cell lineages, lymphocyte‐mediated cytotoxicity occurs in the context of an inflammatory response and the dying cells are lysed into the surroundings rather than phagocytosed. The roles of the two different forms of lymphocyte‐mediated cytotoxicity are quite distinct; however they both involve induction of an endogenous pathway of apoptosis in the targeted cell, and they do share features with all other forms of physiological cell death. (shrink)

The aging process involves changes in immune regulation, i.e. adaptive immunity declines whereas innate immunity becomes activated. NF‐κB signaling is the master regulator of the both immune systems. Two recent articles highlight the role of the NF‐κB system in aging and immune responses. Adler et al1 showed that the NF‐κB binding domain is the genetic regulatory motif which is most strongly associated with the aging process. Kwon et al2 studying HIV‐1 infection and subsequent immune deficiency process (...) demonstrated that HIV‐1 Tat protein binds to SIRT1 protein, a well‐known longevity factor, and inhibits the SIRT1‐mediated deacetylation of the p65 component of the NF‐κB complex. As a consequence, the transactivation efficiency of the NF‐κB factor was greatly potentiated, leading to the activation of immune system and later to the decline of adaptive immunity. These observations support the scenario where immune responses and aging process can be enforced by the potentiation of NF‐κB transactivation efficiency. Longevity factors, such as SIRT1 and its activators, might regulate the efficiency of the NF‐κB signaling, the major outcome of which is inflamm‐aging via proinflammatory responses. BioEssays 30:939–942, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

Many functional glycoproteins are expressed on the lymphocyte cell surface. Some of them carry O-linked oligosaccharides (O-glycans), which are conjugated through serine or threonine residues. During various biological processes, including T-cell activation, a tetrasaccharide on the T-cell surface is dramatically converted to a branched hexasaccharide, called core2 O-glycan. The same structural change in O-glycans is also found on the lymphocytes from patients with immunodeficiency conditions such as Wiskott-Aldrich syndrome and AIDS. Several studies revealing the roles of core2 O-glycans in (...) class='Hi'>immune responses show that this is a biologically significant change. In particular, core2 O-glycans expressed on the cell surface reduce cell–cell interactions, thereby regulating immune responses. Furthermore, core2 O-glycan is a key backbone structure in forming selectin ligands. Thus, O-linked oligosaccharides, in particular those containing core2 branches, play vital roles in immune responses and may play dual roles in certain situations. This review will summarize the results obtained from various studies investigating the roles of O-glycans in immunological processes. BioEssays 23:46–53, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

Many functional glycoproteins are expressed on the lymphocyte cell surface. Some of them carry O-linked oligosaccharides (O-glycans), which are conjugated through serine or threonine residues. During various biological processes, including T-cell activation, a tetrasaccharide on the T-cell surface is dramatically converted to a branched hexasaccharide, called core2 O-glycan. The same structural change in O-glycans is also found on the lymphocytes from patients with immunodeficiency conditions such as Wiskott-Aldrich syndrome and AIDS. Several studies revealing the roles of core2 O-glycans in (...) class='Hi'>immune responses show that this is a biologically significant change. In particular, core2 O-glycans expressed on the cell surface reduce cell–cell interactions, thereby regulating immune responses. Furthermore, core2 O-glycan is a key backbone structure in forming selectin ligands. Thus, O-linked oligosaccharides, in particular those containing core2 branches, play vital roles in immune responses and may play dual roles in certain situations. This review will summarize the results obtained from various studies investigating the roles of O-glycans in immunological processes. BioEssays 23:46–53, 2001. © 2001 John Wiley & Sons, Inc. (shrink)

In this paper, we hypothesize that X chromosome-associated mechanisms, which affect X-linked genes and are behind the immunological advantage of females, may also affect X-linked microRNAs. The human X chromosome contains 10% of all microRNAs detected so far in the human genome. Although the role of most of them has not yet been described, several X chromosome-located microRNAs have important functions in immunity and cancer. We therefore provide a detailed map of all described microRNAs located on human and mouse X (...) chromosomes, and highlight the ones involved in immune functions and oncogenesis. The unique mode of inheritance of the X chromosome is ultimately the cause of the immune disadvantage of males and the enhanced survival of females following immunological challenges. How these aspects influence X-linked microRNAs will be a challenge for researchers in the coming years, not only from an evolutionary point of view, but also from the perspective of disease etiology. (shrink)

Mycobacterium tuberculosis is the causative agent of pulmonary tuberculosis which has infected one third of the mankind and causes 2–3 million deaths worldwide each year. The persistence of the infection ensues from the ability of M. tuberculosis to subvert host immune responses in favor of survival and growth of mycobacteria in macrophages. The mechanisms by which M. tuberculosis manipulates the host immune system have only recently come to light. These activities are attributed to lipoarabinomannans (LAM) and their precursors (...) lipomannans (LM), two predominant glycolipids of M. tuberculosis cell wall. LM are able to skew anti‐mycobacterial immune responses into un‐protective ones, while LAM evoke immunosupression upon binding to macrophage and dendritic cell receptors specialized in binding to “self” host components. A newly emerging idea implicates plasma membrane rafts in LM and LAM signaling. Depending on acylation patterns, the glycolipids may either directly incorporate into the raft membrane via mannosylphosphatidylinositol anchors or interact with raft‐associated proteins to affect the assembly of receptor signaling complexes. BioEssays 30:943–954, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

An important aspect of the developmental maturation of lymphocytes is their capacity to locate and enter lymphoid organs with great rapidity and specificity and to follow certain routes within these organs for the attainment of particular immunological capabilities. It is now known that this “homing response” to lymphoid organs involves specific glycoprotein receptors on the lymphocyte cell surface. The biochemistry of these receptors and their significance in normal and pathological immune responses are discussed.

There can be no doubt that a closer study of avidity will be an indispensable step towards understanding the mechanisms of immunity. N. K. Jerne, 1951, p. 1403.

Behavioral immune system describes psychological mechanisms that detect cues to infectious pathogens in the immediate environment, trigger disease-relevant responses and facilitate behavioral avoidance/escape. BIS activation elicits a perceived vulnerability to disease which can result in conformity with social norms. However, a response to superficial cues can result in aversive responses to people that pose no actual threat, leading to an aversion to unfamiliar others, and likelihood of prejudice. Pathogen-neutralizing behaviors, therefore, have implications for social interaction as well as (...) illness behaviors and responses to health communications. In this study, we investigate how PVD influences conformity, attitudes to other people and to lockdown regulations through the lens of the Reinforcement Sensitivity Theory. RST describes personality in terms of biologically-driven approach and avoidance motivations which support personal goals. Participants from the United Kingdom public completed an RST personality questionnaire and then read either coronavirus morbidity-mortality statistics and current United Kingdom government lifestyle regulations, just the regulations, or no information at all. They all completed the Perceived Vulnerability to Disease scale to assess BIS-relevant Germ Aversion and Perceived Infectability, followed by questions measuring social conformity, warmth toward others and attitudes toward lockdown measures. Significantly lower PVD scores were observed in the no-information condition, with the other conditions showing no difference. In terms of RST, approach behaviors related to goal-drive persistence work alongside fear in explaining conformity to social norms. Reward related approach behaviors partially explained warmth toward others, indicating that social rewards gained through interaction continue to be strong drivers of behavior. We found no role for RST traits in attitudes toward lockdown. Overall, coronavirus-related behavior is not driven purely by fear, but also by social and/or protection goals regulated by approach motivation. This study presents new insights into public perceptions of coronavirus and government regulated lifestyle restrictions, helping to explain social behaviors in terms of biologically driven mechanisms. Such understanding is vital if we are to successfully motivate public behavior to constrain spread of the virus. (shrink)

Niels Kaj Jerne has proposed the “immune network theory” of interactions among anti‐idiotypic antibodies, able to interfere with humoral responses to certain antigens. After the occurrence of the primary generation of antibodies, against an antigenic epitope, idiotypes of these antibodies induce anti‐idiotypic antibodies that modulate the intensity of the first response, and so on. Adverse effects following SARS‐COV‐2 COVID‐19 vaccines are occasionally similar to the symptoms of COVID‐19 infection. Rare events linked to SARS‐CoV‐2 vaccines also resemble some rarely (...) reported COVID‐19 complications. Safety data from product information by European Medicines Agency suggest that spectra do overlap for four main vaccines. The proposition is that vaccine events and COVID‐19 complications are related to anti‐idiotypic antibodies whose spatial shape can lead to interactions with ACE2 molecules, in individuals with a prolonged Spike protein synthesis. The vaccines target cells by their affinity to the vaccine vector, or to engulf lipid nanoparticles. Anti‐idiotypic antibodies shaped similarly to the Spike protein possibly interact with ACE2 molecules and cause diverse signs and symptoms. (shrink)

This article examines discourse on immunity in general public engagements with pandemic influenza in light of critical theory on immuno-politics and bodily integrity. Interview and focus group discussions on influenza with members of the general public reveal that, despite endorsement of government advice on how to avoid infection, influenza is seen as, ultimately, unavoidable. In place of prevention, members of the general public speak of immunity as the means of coping with influenza infection. Such talk on corporeal life under microbial (...) threat is informed by self/not-self, network and ‘choice’ immunity, and therefore makes considerable allowance for cosmopolitan traffic with others, microbes, ‘dirt’ and immune-boosting consumer products. The immuno-political orientation of members of the general public, therefore, appears to trend towards a productive cosmopolitanism that contrasts with more orthodox bioscientific and governmental approaches to pandemic influenza. We reflect on the implications of the immuno-cosmopolitanism of everyday life for the advent of global public health emergency and for biopolitical rule in general. (shrink)

You are, I suspect, exceedingly good at knowing what you intend to do. In saying this I pay you no special compliment. Knowing what one intends is the normal state to be in. And this cries out for some explanation. How is it that we are so authoritative about our own intentions? There are two different approaches that one can take in answering this question. The first credits us with special perceptual powers which we use when we examine our own (...) minds. On this view we detect our own mental states in much the same way that we detect the state of the world around us; but the powers we direct inward are much less prone t o error than those we direct outwards. The alternative approach denies that there is such a thing as inward perception. On this view the whole idea the we detect our own mental states using some kind of internal perceptual apparatus is misguided; a wholly different account is needed. (shrink)

Many areas of business ethics research are “sensitive.” We provide an empirical assessment of the randomized response technique which providesabsoluteanonymity to subjects and “legal immunity” to the researcher. Beyond that, RRT techniques provide complete disclosure to subjects, unconditional privacy is maintained, and there is no deception.

Many areas of business ethics research are “sensitive.” We provide an empirical assessment of the randomized response technique which providesabsoluteanonymity to subjects and “legal immunity” to the researcher. Beyond that, RRT techniques provide complete disclosure to subjects, unconditional privacy is maintained, and there is no deception.

In this paper I examine the claim that businesspersons have what might be called "ethical immunity" with respect to the duty not to deceive. According to this ethical immunity claim, businesspersons are exempt from the ordinary ethical prohibition against deception; and widespread business deception is therefore ethically permissible. I focus on two arguments for the claim. One of the arguments, which has been presented by Albert Carr, relies upon an analogy between business on the one hand, and games in which (...) deception is permitted, on the other. The second argument is based upon the notion that exceptions to ethical duties may sometimes be justified on prudential grounds. In response to the arguments, I try to show that neither one provides strong support for the ethical immunity claim. (shrink)

This study analyzes the relevance in the art world of an ethical and juridical category as the responsibility, as well as its content and limits. The acceptance of the idea of responsibility of the artists depends on the manner in which the “art world” and its frontiers are comprehended - as an autonomous and closed realm or, on the contrary, as a space open to the public control. If the modernist logic of the autonomy had led to the emergence of (...) an artist who claims to an immunity/ impunity based on the absolute artistic freedom, the other model of the art world implies legitimately ethical and juridical questions, as well as an active relation between the public and the forms of the contemporary art. Still, the idea of responsi- bility is tighten to the mode of evaluating the powers of art. As soon as the social and political utility of the art is invoked, it ceased to be not only beyond the good or evil, but also beyond desirable and undesirable, and the responsibility of the artists belongs not only to the aesthetic realm but also to the political one. (shrink)

In this paper we address the issue of how to think about immunity. Many immunological writings suggest a straightforward option: the view that the immune system is primarily a system of defense, which naturally invites the talk of strong immunity and strong immune response. Despite their undisputable positive role in immunology, such metaphors can also pose a risk of establishing a narrow perspective, omitting from consideration phenomena that do not neatly fit those powerful metaphors. Building on this (...) analysis, we argue two things. First, we argue that the immune system is involved not only in defense. Second, by disentangling various possible meanings of ‘strength’ and ‘weakness’ in immunology, we also argue that such a construal of immunity generally contributes to the distortion of the overall picture of what the immune system is, what it does, and why it sometimes fails. Instead, we propose to understand the nature of the immune system in terms of contextuality, regulation, and trade-offs. We suggest that our approach provides lessons for a general understanding of the organizing principles of the immune system in health and disease. For all this to work, we discuss a wide range of immunological phenomena. (shrink)

We would like to thank each of the commentators on our feature article for their thoughtful engagement with our arguments. All the commentaries raise important questions about our proposed justification for natural immunity exemptions to COVID-19 vaccine mandates. Thankfully, for some of the points raised, we can simply signal our agreement. For instance, Reiss is correct to highlight that our article did not address the important US-centric considerations she helpfully raises and fruitfully discusses. We also agree with Williams about the (...) need to provide a clear rationale for mandates, and to obtain different kinds of data in support of possible policies.Unfortunately, we lack the space to engage with every one of the more critical comments raised in this rich set of commentaries; as such, in this response, we shall focus on a discussion of hybrid immunity, which underlies a number of different arguments evident in the commentaries, before concluding with some reflections responding to Lipsitch’s concern about the appropriate standard of proof in this context. (shrink)

Immune cells are highly dynamic in their response to the tissue environment. Most immune cells rapidly change their metabolic profile to obtain sufficient energy to engage in defensive or homeostatic processes. Such “immunometabolism” is governed through intermediate metabolites, and has a vital role in regulating immune‐cell function. The underlying metabolic reactions are shaped by the abundance and accessibility of specific nutrients, as well as the overall metabolic status of the host. Here, we discuss how different (...) class='Hi'>immune‐cell types gain a sufficient energy supply. We then explain how immune cells perform various functions under challenged conditions and expend energy to sustain homeostasis. Finally, we speculate on how the immune‐cell metabolic profile might be modulated in health and disease, by manipulating nutrient availability. By such intervention, the recovery of patient with dysregulated immune system responses might be sped up and the fitness of an individual efficiently restored. (shrink)

In the following excerpt from Bios, Esposito sketches the template of immunity as a response to what he calls a "hermeneutic block" in Foucault's notion of biopolitics. After singling out those moments of greatest tension in Foucault's reading of biopolitics especially as it relates to Nazi thanatopolitics, Esposito sets out in detail the most important features of what he calls the immunization paradigm. Consisting of three dispositifs, namely sovereignty, property, and liberty, the immunitary paradigm has for Esposito a decisively (...) modern inflection. Indeed modern biopolitics cannot be thought apart from the mode by which communities immunize or protect themselves. (shrink)

In recent years, immune systems have sparked considerable interest within the philosophy of science. One issue that has received increased attention is whether other phyla besides vertebrates display an adaptive immune system. Particularly the discovery of CRISPR-Cas9-based systems has triggered a discussion about how to classify adaptive immune systems. One question that has not been addressed yet is the transgenerational aspect of the CRISPR-Cas9-based response. If immunity is acquired and inherited, how to distinguish evolutionary from immunological (...) adaptation? To shed light on this issue and obtain conceptual clarity, I will investigate the inheritance of small RNA responses to pathogens in the nematode C. elegans as a further potential instantiation of a transgenerational adaptive immune system. I will explore how to make sense of systems that lie at the crossroads between genetic, immunological, and evolutionary spheres and explore the consequences of a transgenerational perspective on immune systems for immunology and its philosophy. (shrink)

Host‐pathogen arms race is a universal, central aspect of the evolution of life. Most organisms evolved several distinct yet interacting strategies of anti‐pathogen defense including resistance to parasite invasion, innate and adaptive immunity, and programmed cell death (PCD). The PCD is the means of last resort, a suicidal response to infection that is activated when resistance and immunity fail. An infected cell faces a decision between active defense and altruistic suicide or dormancy induction, depending on whether immunity is “deemed” (...) capable of preventing parasite reproduction and consequent infection of other cells. In bacteria and archaea, immunity genes typically colocalize with PCD modules, such as toxins‐antitoxins, suggestive of immunity‐PCD coupling, likely mediated by shared proteins that sense damage and “predict” the outcome of infections. In type VI CRISPR‐Cas systems, the same enzyme that inactivates the target RNA might execute cell suicide, in a case of ultimate integration of immunity and PCD. (shrink)

It has long been taken for granted that the immune system’s capacity to protect an individual from infection and disease depends on the power of the system to distinguish between self and nonself. However, accumulating data have undermined this fundamental concept. Evidence against the self/nonself discrimination model left researchers in need of a new overarching framework able to capture the immune system’s reactivity. Here, I highlight that along with the self/nonself model, another powerful representation of the immune (...) system’s reactivity has been developed in the twentieth century immunology. According to this alternative view, the immune system is not a killer of nonself strangers but a peace-maker helping to establish harmony with the environment. The balance view of the system has never become part of the dominant paradigm. However, it is gaining more and more currency as new research develops. Advances in mucosal immunology confirm that instead of distinguishing between self and foreign the immune system reacts to microbial, chemical and self-induced alterations to produce responses that counterbalance effects of these changes. (shrink)

© 2015 Elsevier Inc.Postnatal organogenesis occurs in an immune competent environment and is tightly controlled by interplay between positive and negative regulators. Innate immune cells have beneficial roles in postnatal tissue remodeling, but roles for the adaptive immune system are currently unexplored. Here we show that adaptive immune responses participate in the normal postnatal development of a non-lymphoid epithelial tissue. Since the mammary gland is the only organ developing predominantly after birth, we utilized it as a (...) powerful system to study adaptive immune regulation of organogenesis. We found that antigen-mediated interactions between mammary antigen-presenting cells and interferon-γ -producing CD4+ T helper 1 cells participate in MG postnatal organogenesis as negative regulators, locally orchestrating epithelial rearrangement. IFNγ then affects luminal lineage differentiation. This function of adaptive immune responses, regulating normal development, changes the paradigm for studying players of postnatal organogenesis and provides insights into immune surveillance and cancer transformation. Plaks et al. (shrink)

Stress-induced brain-mediated immunoregulation is effected by two pathways: autonomic outflow and (neuro)endocrine outflow. Particular attention is given to the interaction-effects of chronic an acute stress. Recent data have established that cells of the immune system produce neuro-peptides and hormones. In concert with cytokines released by these immune cells the brain can be informed on the nature of ongoing immune activity. The significance of conditioning of immune responses is discussed.

The current SARS-CoV-2 pandemic has killed thousands across the world. SARS-CoV-2 is the latest but surely not the last such global pandemic we will face. The biomedical response to such pandemics includes treatment, vaccination, and so on. In this paper, though, we argue that it is time to consider an additional strategy: the somatic enhancement of human immunity. We argue for this approach and consider bioethics objections we believe can be overcome.

Trust has been widely investigated both theoretically and empirically. Whether thought of as the result of a calculation of costs/benefits, a shared identity, or a leap of faith, there always seems to be an ‘as if’ rhetorical gesture which is ultimately needed to explain how actors move from the base of trust to expectations of trust via suspending judgment on uncertainty and fear of vulnerability to betrayal and exploitation — the actors ultimately act ‘as if’ they do not fear uncertainty (...) and vulnerability to betrayal. Yet this ‘as if’ element has remained seriously under-theorised. Drawing on Derrida's deconstruction, I propose a way of thinking this ‘as if’ element of trust. I thus argue that the decision to trust occurs in a terrain of structural undecidability. The latter is thought of as the possibility condition of trust as well as the subject of trust and a sense of responsibility for this trust. The aporiatic nature of undecidability makes this trust an auto-immune trust which obeys the tripartite logic of ‘without’ which both negates and affirms trust. (shrink)

The question of the morality of war is something of an embarrassment to liberal political thinkers. A philosophical tradition which aspires to found its preferred institutions in respect for individual autonomy, contract, and voluntary association, is naturally confronted by a phenomenon that is almost exclusively explained and justified in the language of States, force and territory. But the apparent difficulties involved in providing a convincing account of nature and ethics of war in terms of relations between individuals has not prevented (...) liberal theorists from attempting this task. This paper examines a recent attempt by Igor Primoratz to sketch out the implications of a consistent liberalism for just war doctrine and, in particular, as regards the question of who may be a legitimate target of attack in wartime. Primoratz’s paper itself is a critique of Michael Waltzer’s authoritative exposition of just war theory for failing to be sufficiently and consistently liberal. The debate between these two authors is a productive site for investigating the potential and limitations of liberal theories of just war. (shrink)

Both concepts of the holobiont and the immune system are at the heart of an ongoing scientific and philosophical examination concerning questions of the organism’s individuality and identity as well as the relations between organisms and their environment. Examining the holobiont, the question of boundaries and individuality is challenging because it is both an assemblage of organisms with physiological cohesive aspects. I discuss the concept of immunity and the immune system function from the holobiont perspective. Because of the (...) host-microbial close relations of codependence and interdependence, the holobiont is more often than not confused with the host, as the host is the domain in which this entity exists. I discuss the holobiont unique ecological characteristics of microbial assemblages connected to a host in a network of interactions in which the host is one of the organisms in the community but also its landscape. Therefore, I suggest viewing the holobiont as a host-ecosystem and discuss the implication of such a view on the concept of immunity and the meaning of protection. Furthermore, I show that viewing the holobiont as a host ecosystem opens the possibility of using the same ecological definition of boundaries and immunity dealing with an ecological system. Thus, the holobiont’s boundaries and immunity are defined by the persistence of its complex system of interactions integrating existing and new interactions. This way of thinking presents a notion of immunity that materializes as the result of the complex interdependence relations between the different organisms composing the holobiont similar to that of an ecosystem. Taking this view further, I discuss the notion of immunogenicity that is ontologically heterogeneous with various causal explanations of the processes of tolerance and targeted immune response. Finally, I discuss the possible conceptualization of already existing and new biomedical practices. (shrink)

In biology, the ‘ecological orientation' rests on a commitment to examining systems, and the conceptual challenge of defining that system now employs techniques and concepts adapted from diverse disciplines (i.e., systems philosophy, cybernetics, information theory, computer science) that are applied to biological simulations and model building. Immunology has joined these efforts, and the question posed here is whether the discipline will remain committed to its theoretical concerns framed by the notions of protecting an insular self, an entity demarcated from its (...) environment, or will shift its focus of interest to a wider context. An ecological perspective emphasizes the interchange between the organism and its environment, the processing of information, and the regulation arising from responses to this larger context. Moving from the first attempts at modeling the immune system as a closed network, immunologists have joined the general interest in systems analysis, and that move might portend a significant shift to an open, more holistic consideration of immune regulation. *Received December 2006; revised August 2007. †To contact the author, please write to: Center for Philosophy and History of Science, Boston University, 745 Commonwealth Ave., Boston, MA 02215; e-mail: [email protected]. (shrink)