Cancer cells seem to exploit mechanisms that evolve as part of physiological tolerance, which is a complementary and often beneficial form of defense. The study of physiological systems of tolerance can therefore provide insights into the development of a state of host tolerance of cancer, and how to break it. Analysis of these models has the potential to improve our understanding of existing immunological therapeutic targets, and help to identify future targets and rational therapeutic combinations. The treatment of cancer with (...) immune checkpoint inhibitors aims to reverse the progression to tolerance of cancer, and achieve an immunogenic, rather than tolerogenic, homeostasis. Broadening the efficacy and durability of checkpoint inhibitors focuses on reversing tolerance and stimulating immunogenicity in the cancer, host, and environment. Two examples of important physiological states of tolerance that may inform tolerance of cancer are microbial infection and placental reproduction. These states of tolerance result from bilateral shaping of host and non‐self, akin to immunoediting in cancer, and offer reliable models to study the immune tolerance paradigm. (shrink)

T cells, which are derived from hematopoietic stem cells (HSCs), are the most important components of adaptive immune system. Based on the expression of αβ and γδ receptors, T cells are mainly divided into αβ and γδ T cells. In the thymus, they share common progenitor cells, while undergoing a series of well‐characterized and different developmental processes. N6‐Methyladenosine (m6A), one of the most abundant modifications in mRNAs, plays critical roles in cell development and maintenance of function. Recently, we have (...) demonstrated that the depletion of m6A demethylase ALKBH5 in lymphocytes specifically induces an expansion of γδ T cells through the regulation of Jag1/Notch2 signaling, but not αβ T cells, indicating a checkpoint role of ALKBH5 and m6A modification in the early development of γδ T cells. Based on previous studies, many key pathway molecules, which exert dominant roles in γδ T cell fate determination, have been identified as the targets regulated by m6A modification. In this review, we mainly summarize the potential regulation between m6A modification and these key signaling molecules in the γδ T cell lineage commitment, to provide new perspectives in the checkpoint of γδ T cell development. (shrink)

During tumor evolution, cancer cells use the tumor‐stroma crosstalk to reorganize the microenvironment for maximum robustness of the tumor. The success of immune checkpoint therapy foretells a new cancer therapy paradigm: an effective cancer treatment should not aim to influence the individual components of super complex intracellular interactomes (molecular targeting), but try to disrupt the intercellular interactions between cancer and stromal cells, thus breaking the tumor as a whole. Arguments are provided in favor of a hypothesis that such interactions (...) include formation of synapse‐like structures (interfaces) where the interacting cells are located at a distance of ∼10–15 nm. Within these interfaces, molecules initiating and strengthening the interaction are organized, and allow optimum cross‐signaling; a very confined intercellular space facilitates the concentration of secreted cytokines, enhancing the paracrine cross‐communication. These features of tumors form a druggable cancer hallmark the tumor‐stroma symbiotic crosstalk—which represents a new target for efficient cancer drug discovery. (shrink)

The ATM protein kinase is centrally involved in the cellular response to ionizing radiation (IR) and other DNA double‐strand‐break‐inducing insults. Although it has been well established that IR exposure activates the ATM kinase domain, the actual mechanism by which ATM responds to damaged DNA has remained enigmatic. Now, a landmark paper provides strong evidence that DNA‐strand breaks trigger widespread activation of ATM through changes in chromatin structure.1 This review discusses a checkpoint activation model in which chromatin perturbations lead to the (...) conversion of inactive ATM domains to phosphorylated, active ATM monomers. The new findings underscore the critical importance of epigenetic events in genome function and surveillance in mammalian cells. BioEssays 25:627–630, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

In Immunity, Alfred Tauber sets forth a new theory of immunology that rejects the common principle of self and non-self, and the immune system's role as a protector of the self from external threats. Rather than serving to defend an independent entity, he argues, immunity participates in a large, complex eco-system of porous and flexible boundaries. Tauber's new approach to immunology necessitates a new biology in which symbiosis is the rule, not the exception.

An immunizing strategy is an argument brought forward in support of a belief system, though independent from that belief system, which makes it more or less invulnerable to rational argumentation and/or empirical evidence. By contrast, an epistemic defense mechanism is defined as a structural feature of a belief system which has the same effect of deflecting arguments and evidence. We discuss the remarkable recurrence of certain patterns of immunizing strategies and defense mechanisms in pseudoscience and other belief systems. Five different (...) types will be distinguished and analyzed, with examples drawn from widely different domains. The difference between immunizing strategies and defense mechanisms is analyzed, and their epistemological status is discussed. Our classification sheds new light on the various ways in which belief systems may achieve invulnerability against empirical evidence and rational criticism, and we propose our analysis as part of an explanation of these belief systems’ enduring appeal and tenacity. (shrink)

Here we discuss a “chromosome separation checkpoint” that might regulate the anaphase‐telophase transition. The concept of cell cycle checkpoints was originally proposed to account for extrinsic control mechanisms that ensure the order of cell cycle events. Several checkpoints have been shown to regulate major cell cycle transitions, namely at G1‐S and G2‐M. At the onset of mitosis, the prophase‐prometaphase transition is controlled by several potential checkpoints, including the antephase checkpoint, while the spindle assembly checkpoint guards the metaphase‐anaphase (...) transition. Our hypothesis is based on the recently uncovered feedback control mechanism that delays chromosome decondensation and nuclear envelope reassembly until effective separation of sister chromatids during anaphase is achieved. A central player in this potential checkpoint is the establishment of a constitutive, midzone‐based Aurora B phosphorylation gradient that monitors the position of chromosomes along the spindle axis. We propose that this surveillance mechanism represents an additional step towards ensuring mitotic fidelity. (shrink)

This paper responds to arguments due to Joel Smith and Annalisa Coliva that try to show that James Pryor’s notion of wh-misidentification is philosophically uninteresting, and perhaps even spurious. It also proposes definitions of wh-misidentification and immunity to wh-misidentification which try to improve in various ways on the characterisations that standardly figure in the literature, and explores the relationship between misidentification and the epistemic structures characteristic of some kinds of Gettier cases.

Bacterial checkpoints, analogous to those proposed to exist in eukaryotic cells, offer insights into the definition of a checkpoint. Examination of bacterial “checkpoint” or arrest phenomena illustrate problems with a too‐casual application of the checkpoint idea to eukaryotic phenomena. The question raised here is whether there are cellular processes that “check” whether a cellular process is completed. It is possible that many eukaryotic “checkpoints” may not have “checking” functions. Some of the ubiquitous checkpoint phenomena widely described may be (...) merely the result of the inherent incompleteness of earlier events preventing the initiation of subsequent events. BioEssays 28: 1035–1039, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

Bacterial checkpoints, analogous to those proposed to exist in eukaryotic cells, offer insights into the definition of a checkpoint. Examination of bacterial “checkpoint” or arrest phenomena illustrate problems with a too‐casual application of the checkpoint idea to eukaryotic phenomena. The question raised here is whether there are cellular processes that “check” whether a cellular process is completed. It is possible that many eukaryotic “checkpoints” may not have “checking” functions. Some of the ubiquitous checkpoint phenomena widely described may be (...) merely the result of the inherent incompleteness of earlier events preventing the initiation of subsequent events. BioEssays 28: 1035–1039, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

Adaptive immunity provides the unique ability to respond to a nearly infinite range of antigenic determinants. Given the inherent plasticity of the adaptive immune system, a series of tolerance mechanisms exist to reduce reactivity toward self. While this reduces the probability of autoimmunity, it also creates an important gap in adaptive immunity: the ability to recognize microbes that look like self. As a variety of microbes decorate themselves in self‐like carbohydrate antigens and tolerance reduces the ability of adaptive immunity (...) to react with self‐like structures, protection against molecular mimicry likely resides within the innate arm of immunity. In this review, we will explore the potential consequences of microbial molecular mimicry, including factors within innate immunity that appear to specifically target microbes expressing self‐like antigens, and therefore provide protection against molecular mimicry. (shrink)

I argue that immunity to error through misidentification primarily characterizes thoughts that are 'implicitly' de se, as opposed to thoughts that involve an explicit self-identification. Thoughts that are implicitly de se involve no reference to the self at the level of content: what makes them de se is simply the fact that the content of the thought is evaluated with respect to the thinking subject. Or, to put it in familiar terms : the content of the thought is a property (...) which the thinking subject self-ascribes (as in the Loar/Lewis/Chisholm analysis). After answering an objection (to the effect that immunity can affect explicit de se thoughts), I extend the analysis to demonstrative thoughts, which also exhibit the property of immunity to error through misidentification. (shrink)

Any plausible position in the ethics of war and political violence in general will include the requirement of protection of civilians (non-combatants, common citizens) against lethal violence. This requirement is particularly prominent, and particularly strong, in just war theory. Some adherents of the theory see civilian immunity as absolute, not to be overridden in any circumstances whatsoever. Others allow that it may be overridden, but only in extremis. The latter position has been advanced by Michael Walzer under the heading of (...) “supreme emergency.” In this paper, I look into some of the issues of interpretation and application of Walzer’s “supreme emergency” view and some of the criticisms that have been levelled against it. I argue that Walzer’s view is vague and unacceptable as it stands, but that the alternatives proposed by critics such as Brian Orend, C.A.J. Coady, and Stephen Nathanson are also unattractive. I go on to construct a position that is structurally similar to Walzer’s, but more specific and much less permissive, which I term the “moral disaster” view. According to this view, deliberate killing of civilians is almost absolutely wrong. (shrink)

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)

In this paper I aim to illuminate the significance of thought insertion for debates about the first-person concept. My starting point is the often-voiced contention that thought insertion might challenge the thesis that introspection-based self-ascriptions of psychological properties are immune to error through misidentification relative to the first-person concept. In the first part of the paper I explain what a thought insertion-based counterexample to this immunity thesis should be like. I then argue that various thought insertion-involving scenarios do not (...) give rise to successful counterexamples to the immunity of the target class of self-ascriptions. In the second part of the paper I turn to defend a Metasemantic Explanation of why the immunity thesis holds. The Metasemantic Explanation rests on a reference-fixing story about the mental ‘I’ whose key contention is that introspective impressions play an essential role in fixing its reference. It is part of my argument in favour of the proposed reference-fixing story, as well as of the Metasemantic Explanation, that they respect the paradigmatic features of self-ascriptions of inserted thoughts. (shrink)

In this collection of newly commissioned essays, the contributors present a variety of approaches to it, engaging with historical and empirical aspects of the subject as well as contemporary philosophical work.

Are bodily self-ascriptions immune to error through misidentification? According to the Inside mode view, one cannot be mistaken about whose body part it is when experiencing them from the inside. Here I shall consider two possible objections to bodily immunity. On the one hand, I shall briefly envisage two cases of misidentification: somatoparaphrenia and the Rubber Hand illusion. I shall show that none of them challenges the immunity principle. On the other hand, I shall highlight a more serious issue (...) for bodily immunity, namely, the multimodal nature of bodily self-knowledge. Very few bodily self-ascriptions are based on grounds that are purely or exclusively from the inside. I shall evaluate the consequences of multimodality for bodily immunity. (shrink)

In nature, cells face a variety of stresses that cause physical damage to the plasma membrane and cell wall. It is well established that evolutionarily conserved cell cycle checkpoints monitor various cellular perturbations, including DNA damage and spindle misalignment. However, the ability of these cell cycle checkpoints to sense a damaged plasma membrane/cell wall is poorly understood. To the best of our knowledge, our recent paper described the first example of such a checkpoint, using budding yeast as a (...) model. In this review, we will discuss this important question as well as provide hypothetical explanations to be tested in the future. (shrink)

Judgments based on episodic memory are often thought to be immune to errors of misidentification (IEM). Yet there is a certain category of episodic memories, viz. observer memories, that seems to threaten IEM. In the resulting debate, some say that observer memories are a threat to the IEM enjoyed by episodic memory (Michaelian, 2021); others say that they pose no such threat (Fernández, 2021; Lin, 2020). In this paper, we argue for a middle way. First, we frame the debate, (...) claiming that the existing literature lacks a satisfying definition both of observer memories and of the precise issue of errors of identification in such memories. Then, we contribute to the debate by challenging an anti-separatist view about the relation between phenomenal and intentional features of observer memories that looms behind this debate. On this view, if the rememberer's self is a phenomenal feature of the memory, by implication it is also built into the intentional content. We reject this view and offer a moderate separatist account. Distinguishing between empirically-grounded species of observer memories, we say that the phenomenal self sometimes is, and sometimes is not built into the intentional content of the memory, and this results in different implications for IEM. (shrink)

Cell cycle arrest in M phase can be induced by the failure of a single chromosome to attach properly to the mitotic spindle. The same cell cycle checkpoint mediates M phase arrest when cells are treated with drugs that either disrupt or hyperstabilize spindle microtubules. Study of yeast mutants that fail to arrest in the presence of microtubule disruptors identified a set of genes important in this checkpoint pathway. Two recent papers report the cloning of human and Xenopus homologues of (...) one of these yeast genes, called MAD2 (for mitotic arrest deficient‐2)(1,2). Introduction of antibodies to the MAD2 protein into living mammalian cells or Xenopus egg extracts abrogates the M phase arrest induced by microtubule inhibitors. This and other recent developments suggest a model for the M phase checkpoint in which unattached kinetochores inhibit the ubiquitination of proteins whose proteolysis is necessary for chromatid separation and exit from mitosis. (shrink)

Three major aspects of G1 regulation acting at START in fission yeast are discussed in this review. Firstly, progression towards S phase in the mitotic cycle. This is controlled by the activation of transcription complexes at START which cause cell cycle‐dependent activation of genes required for DNA synthesis. The second aspect is the regulation of developmental fate occurring during G1. Passage through START appears to inhibit sexual differentiation because the meiotic and mitotic pathways are mutually exclusive. This is brought about (...) because the meiotic pathway is inhibited by the same gene functions that are required for S phase onset. Thirdly, distinct checkpoint, or dependency, controls operate both pre‐ and post‐START in the mitotic cycle to inhibit mitosis in the absence of replicated DNA, and also to limit rounds of DNA replication to one per cell cycle. (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)

How chromatin bridges are detected by the abscission checkpoint during mammalian cell division is unknown. Here, we discuss recent findings from our lab showing that the DNA topoisomerase IIα (Top2α) enzyme binds to catenated (“knotted”) DNA next to the midbody and forms abortive Top2‐DNA cleavage complexes (Top2ccs) on chromatin bridges. Top2ccs are then processed by the proteasome to promote localization of the DNA damage sensor protein Rad17 to Top2‐generated double‐strand DNA ends on DNA knots. In turn, Rad17 promotes local recruitment (...) of the MRN protein complex and downstream ATM‐Chk2‐INCENP signaling to delay abscission and prevent chromatin bridge breakage in cytokinesis. (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 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)

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)

After two years of global pandemic, it is no surprise that immunization is now at the center of our experience. From the medicalization of politics to the disciplining of individuals, from lockdowns to mass vaccination programs, contemporary societies seem to be firmly embedded in a syndrome of immunity. To understand the ambivalent effects of this development, it is necessary to go back to its modern genesis, when the languages of law, politics, and medicine began to merge into the biopolitical regime (...) we have been living under for some time. This regime places a high priority on immunization and security: no security is more important than health security. The Covid-19 pandemic has taken the dynamic of immunization to a new level: for the first time in history, we see societies seeking to achieve generalized immunity in their entire populations through vaccination. This allows us to glimpse the possibility of a “common immunity” that strengthens the relation between community and immunity. The dramatic tensions we have experienced in recent years between security and freedom, norm and exception, power and existence, all refer to the complex relationship between community and immunity, the decisive features of which are reconstructed in this book. Building on the prescient argument originally developed two decades ago in Immunitas, Roberto Esposito demonstrates in this new book how the pandemic and our responses to it have brought into sharp relief the fundamental biopolitical conditions of our contemporary societies. (shrink)

Artificial Immune Systems (AIS) are intelligent algorithms derived on the principles inspired by human immune system. In this research work, electroencephalography (EEG) signals for four distinct motor movement of human limbs are detected and classified using Negative Selection Classification Algorithm (NSCA). For this study, a widely studied open source EEG signal database (BCI IV - Graz dataset 2a, comprising 9 subjects) has been used. Mel Frequency Cepstral Coefficients (MFCCs) are extracted as selected feature from recorded EEG signals. Dimensionality (...) reduction of data is carried out by applying two hidden layered stacked auto-encoder. Genetic Algorithm (GA) optimized detectors (Artificial Lymphocytes) are trained using Negative Selection Algorithm (NSA) for detection and classification of four motor movements. The trained detectors consist of four sets of detectors, each set is trained for detection and classification of one of the four movements from the other three movements. The optimized radius of detector is small enough not to mis-detect the sample. Euclidean distance of each detector with every training dataset sample is taken and compared with optimized radius of detector as a non-self detector. Our proposed approach achieved a mean classification accuracy of 86.39% for limb movements over 9 subjects with a maximum individual subject classification accuracy of 97.5 % for subject number eight. (shrink)

This is one of the first books in a new series that will publish the very best work in the philosophy of biology. The series will be non-sectarian in character, will extend across the broadest range of topics, and will be genuinely interdisciplinary. The Immune Self is a critical study of immunology from its origins at the end of the nineteenth century to its contemporary formulation. The book offers the first extended philosophical critique of immunology, in which the function (...) of the term 'self' that underlies the structure of current immune theory is analysed. However, this analysis is carefully integrated into a broad survey of the major scientific developments in immunology, a discussion of their historical context, and a review of the conceptual arguments that have moulded this sophisticated modern science. (shrink)

Saying ┌ that ψ is F ┐ when one should have said ┌ that φ is F ┐ involves making one of two different kinds of error. Either the wrong nominal term (┌ ψ ┐ instead of ┌ φ ┐) is ascribed to the right object or the right nominal term is ascribed to the wrong object. Judgments susceptible to one kind of error are immune to the other. Indexical terms such as ‘here’ and ‘now’ exhibit a corresponding pattern (...) of immunity and susceptibility to error, which suggests that they are complex demonstratives. This should also apply to ‘I’. (shrink)

This is one of the first books in a new series that will publish the very best work in the philosophy of biology. The series will be non-sectarian in character, will extend across the broadest range of topics, and will be genuinely interdisciplinary. The Immune Self is a critical study of immunology from its origins at the end of the nineteenth century to its contemporary formulation. The book offers the first extended philosophical critique of immunology, in which the function (...) of the term 'self' that underlies the structure of current immune theory is analysed. However, this analysis is carefully integrated into a broad survey of the major scientific developments in immunology, a discussion of their historical context, and a review of the conceptual arguments that have moulded this sophisticated modern science. (shrink)

Da Ré and Szmuc argue that while there is a symmetry between ‘infectious’ and ‘immune’ logics, this symmetry fails w.r.t. extending an algebra with an immune or an infectious element. In this paper, I show that the symmetry also fails w.r.t. defining a new logical operation from a given set of primitive (Boolean) operations. I use the case of the material conditional to illustrate this point.

Dependency relationships within the cell cycle allow cells to arrest the cycle reversibly in response to agents or conditions that interfere with specific aspects of its normal progression. In addition, overlapping pathways exist which also arrest the cell cycle in response to DNA damage. Collectively, these control mechanisms have become known as checkpoints. Analysis of checkpoints is facilitated by the fact that dependency relationships within the cell cycle, such as the dependency of mitosis on the completion of DNA (...) synthesis, and the DNA damage checkpoint can be separated genetically. In fission yeast, Schizosaccharomyces pombe, the dependency of mitosis on prior completion of DNA synthesis is mediated through tyrosine‐15 phosphorylation of the ubiquitous mitotic regulator p34cdc2. In contrast, the arrest of mitosis caused by DNA damage acts through a separate mechanism that appears to be independent of tyrosine‐15 phosphorylation. Despite these distinct interactions with the mitotic machinery, the majority of fission yeast mutants that are deficient in mitotic arrest after DNA damage are also unable to respond to inhibition of DNA synthesis. In this essay we survey the current knowledge concerning feedback controls and checkpoints within fission yeast and relate this to information derived from other systems. (shrink)

The concept of regulatory ‘checkpoints’ in the eukaryotic cycle has proved to be a fruitful one. Here, its applicability to the bacterial cell cycle is examined. A primitive DNA damage checkpoint operates in E. coli such that, after exposure to ultraviolet light, while excision repair occurs, chromosome replication continues very slowly with the production of discontinuous daughter strands. The slower the rate of excision of photoproducts, the greater the delay before the normal rate of DNA replication is restored, the (...) additional time for repair ensuring that normal survival is maintained. A model is proposed in which replication rate is controlled by the ratio of RecAcoated to uncoated single stranded regions of DNA in the replication fork. There are also two cell division inhibitors SulA (=SfiA) and SfiC under the control of the SOS system and sensitive to DNA damage, but they are irrelevant to the survival of wild‐type bacteria under normal conditions. In strains where SulA and SfiC do not operate, inhibition is not influenced by the rate of excision repair and so fails one of the criteria for a DNA damage checkpoint, namely the monitoring of the DNA for the level of residual damage. (shrink)

Since Sydney Shoemaker published his seminal article ‘Self-Reference and Self-Awareness’ in 1968, the notion of ‘Immunity to Error through Misidentification’ has received much attention. It crops up in discussions of personal identity, indexical thought and introspection, and has been used to interpret remarks made by philosophers from Wittgenstein to William James. The precise significance of IEM is often unspecified in these discussions, however. It is unclear, for example, whether itconstitutesan important status of judgments, whether itexplainsan important characteristic of judgments, or (...) whether it merelymarksan important characteristic of judgments. Nevertheless, reference to IEM abounds, making this obscure notion seem all the more significant. (shrink)

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.

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)

This article is concerned with an exploration of a family of systems—called immune logics—that arise from certain dualizations of the well-known family of infectious logics. The distinctive feature of the semantic of infectious logics is the presence of a certain “infectious” semantic value, by which two different though equivalent things are meant. On the one hand, it is meant that these values are zero elements for all the operations in the underlying algebraic structure. On the other hand, it is (...) meant that these values behave in a value-in-value-out fashion for all the operations in the underlying algebraic structure. Thus, in a rather informal manner, we will refer to immune logics as those systems whose underlying semantics count with a certain “immune” semantic value behaving in a way that is somewhat dual to that of the infectious values. In a more formal manner, carrying out this dualization will prove to be not as straightforward as one could imagine, since the two characterizations of infectiousness discussed above lead to two different outcomes when one tries to conduct them. We explore these alternatives and provide technical results regarding them, and the various logical systems defined using such semantics. (shrink)

It has been observed that, unlike other kinds of singular judgments, mental self-ascriptions are immune to error through misidentification: they may go wrong, but not as a result of mistaking someone else’s mental states for one’s own. Although recent years have witnessed increasing interest in this phenomenon, three basic questions about it remain without a satisfactory answer: what is exactly an error through misidentification? What does immunity to such errors consist in? And what does it take to explain the (...) fact that mental self-ascriptions exhibit this sort of immunity? The aim of this paper is to bring these questions into focus, propose some tentative answers and use them to show that one prominent attempt to explain the immunity to error through misidentification of mental self-ascriptions is unsuccessful. (shrink)

In this paper we introduce a paradigm of experiment which, we believe, is of interest both in psychology and philosophy. There the subject wears an HMD (head-mount display), and a camera is set up at the upper corner of the room, in which the subject is. As a result, the subject observes his own body through the HMD. We will mainly focus on the philosophical relevance of this experiment, especially to the thesis of so-called 'immunity to error through misidentification relative (...) to the first-person pronoun'. We will argue that one experiment conducted in this setting, which we call the bodily illusion experiment, provides a counterexample to that thesis. (shrink)

Since, it has become clear that individuality is not to be considered as a given, but rather as something which needs to be explained. How has individuality emerged through evolution, and how has it subsequently been maintained? In particular, why is it that multicellular organisms appeared and persisted, despite the obvious interest of each cell of favoring its own replication? Several biologists see the immune system as one of the key components for explaining the maintenance of multicellular organisms’ individuality. (...) Indeed, the immune system exerts a constant surveillance on all the constituents of the organism, including “cheaters” like tumor cells, which favor their own replication at the expense of the whole organism. In most cases, the immune system eliminates those cheaters. This is the “immune surveillance” hypothesis, first suggested by Burnet and Thomas. In this paper, I account for recent findings on immune surveillance in order to determine the precise role of the immune system in the emergence and maintenance of individuality. This investigation gives rise to a critical question for the domain of biological individuality: should immunity be considered as something unique to multicellular organisms? If it is indeed unique, should the multicellular organism be considered as an individual to a higher degree than any other living entity? If it is not unique, what precisely are the equivalents of the immune system in other living individuals? (shrink)

In this article, Roberto Esposito lays out the genealogical pathways linking the three major concepts around which his most recent work has wound its way: community, immunity, and biopolitics. Although immunity is necessary to the preservation of our life, when driven beyond a certain threshold it forces life into a sort of cage where not only our freedom gets lost but also the very meaning of our existence – that opening of existence outside itself that takes the name of communitas. (...) A hermeneutics informed by immunity can allow the category of community to regain a new political significance, without ending up in a substantialist metaphysics. This task is dictated by the urgent need for an affirmative biopolitics – a horizon of meaning – in which life would no longer be the object but somehow the subject of politics. But what sort of shape would this take? Where would we trace its symptoms? And with what objectives? A preliminary answer focuses on breaking the vise grip between public and private that threatens to crush the common, by seeking instead to expand the space of the common, in the fight, for example, against the planned privatization of water and the battle over energy sources. (shrink)

We define and study a new notion called k-immunity that lies between immunity and hyperimmunity in strength. Our interest in k-immunity is justified by the result that θ does not k-tt reduce to a k-immune set, which improves a previous result by Kobzev [7]. We apply the result to show that Φ′ does not btt-reduce to MIN, the set of minimal programs. Other applications include the set of Kolmogorov random strings, and retraceable and regressive sets. We also give a (...) new characterization of effectively simple sets and show that simple sets are not btt-cuppable. (shrink)

The immune system, to protect the body, must discriminate between the pathogenic and non-pathogenic microbes and respond to them in different ways. How the mucosal immune system manages to make this distinction is poorly understood. We suggest here that the distinction between pathogenic and non-pathogenic microbes is made by an integrated system rather than by single types of cells or single types of receptors; a systems biology approach is needed to understand immune recognition.

Intended both as an introduction to the thought of the Italian philosopher Roberto Esposito and as a mapping of current biopolitical practice, this essay traces the contributions and the limits of recent Italian contributions to the discussion of biopolitics. The essay offers a summary of Esposito's insight into the relation of community and immunity and compares his thinking to other philosophers who take immunity as their object of study . Campbell goes on to read Esposito's privileging of bios in the (...) light of Giorgio Agamben's emphasis on zōē, while making reference as well to Antonio Negri and Michael Hardt's understanding of biopower. He concludes by arguing that the stakes of Esposito's analysis for an affirmative biopolitics concern fundamentally the nature of community and its opening to all life forms as bios. (shrink)

The protection of noncombatants from deadly violence is the centrepiece of any account of ethical and legal constraints on war. It was a major achievement of moral progress from early modern times to World War I. Yet it has been under constant attrition since - perhaps never more so than in our time, with its 'new wars', the spectre of weapons of mass destruction, and the global terrorism alert. -/- Civilian Immunity in War, written in collaboration by eleven authors, provides (...) the first comprehensive analysis of all main aspects of this highly topical subject. It considers the arguments for rejection of civilian immunity and the main theories of the grounds and proper scope of this immunity, both deontological (just war theory) and consequentialist. Separate chapters examine the historical development of the idea of civilian immunity, its standing in current international law, and the problem of "collateral damage": of harming civilians without intent, as a side-effect of attacks on military targets. The volume also addresses a string of specific issues. Civilian immunity has undergone much attrition with the development of air warfare and the tendency of military conflict to degenerate into "total" war. On the other hand, modern military technology with its precision guidance missiles and "smart" bombs opens up the possibility of restricting deadly violence to its proper targets and staying clear of civilian life, limb, and property. Another pressing issue is the fate of women in war in light of mass rapes characteristic of some 'new wars'. (shrink)

This article analyzes the issues of content and scope of the immunity of a close person as a witness in criminal procedure of Lithuania. The question on sufficiency of this immunity is raised because protection of a personal and family secret in criminal proceedings depends upon it. The author also perceives uncertainty of the actual and legal status of a close person as a family member, while ascertaining and implementing one of the most important additional guarantees granted for witnesses. The (...) following propositions are formulated: as regards witness’ immunity from obligation to testify against a member of his/her family or against his/her close relative, it is necessary to assess not only the formal aspects of the concepts “family” or “marriage”, but also the actual nature of the relations of persons who are bound by family or similar ties. (shrink)

The article deals with the discussion of the concept and implementation of immunities of the witness in the criminal proceedings in abstracto. The problem is whether the additional guarantee of protection of the witness’ procedural interests, which is fixed in the Law of the Criminal Procedure, is appropriately methodologically regulated, or whether certain immunities of the witness are appropriately perceived and applied in practice, is raised in the present article. Through this reason, the author, searching for the answers to these (...) questions—how is all this and how must all this be?—singles out, in abstracto, two elements of immunities of the witness, in concreto—the immunities of the witness and witnessing. It would seem that these protective guarantees are similar in principle. The analysis of this article allows for the answer that they are analogous from the point of view of their value. However, they differ by the mechanisms of implementation. According to the author, the immunity of the witness protects the person from becoming a witness, whereas the immunity of witnessing secures protection from witnessing, which may cause harm to the witness himself/herself. Accordingly, it also determines the need not only to analyze these two elements, but their interrelation and interrelations as well. (shrink)

Three pathologies of alienation have been claimed to refute the philosophical thesis that introspection-based self-ascriptions of mental states are immune to error through misidentification. In this paper, I show that this critique of the Immunity Thesis is misguided; the cases of alienation either are not self-ascriptions or do not involve misidentification. Rather, these cases undermine a widely assumed explanation of immunity, which is based on the idea that self-ascriptions of mental states are identification-free. I argue that, given a certain (...) understanding of the Immunity Thesis, identification-freedom does not explain immunity anyhow, and I offer an alternative explanation, one which posits a tight link between first-personal awareness and ownership of a mental state. (shrink)