Immunological mechanisms and therapy approaches in psychotic syndromes were recently supported by the discovery of autoantibody-associated limbic and non-limbic encephalitis. However, how clinical diagnostic procedures in psychiatry should be adapted to these new insights is still unclear. In this study, we analyzed the cerebrospinal fluid (CSF) and neuroimmunological alterations and their association with cerebral MRI (cMRI) and electroencephalographic (EEG) findings. From 2006 until 2013, we acquired 180 CSF samples from psychotic patients. Between 2006 and 2009, CSF examinations were only performed (...) in cases in which organic brain disease was suspected. Since then, this procedure has been integrated into our routine diagnostic workup. CSF basic diagnostics were supplemented by measuring antineuronal antibodies against intracellular synaptic antigens, antibodies against intracellular onconeural antigens, antibodies against neuronal cell surface antigens and thyroid antibodies. In addition, cMRIs and EEGs were conducted. We found white cell counts elevated in 3.4% of the cases, albumin quotient elevated in 21.8%, and protein concentration elevated in 42.2%. Evidence of intrathecal immunoglobulin synthesis was found in 7.2% of the cases. Antibodies measured against neuronal cell surface antigens were positive in 3.2%. Reactivity on antibodies against intracellular onconeural antigens were detected in 3.5%. Serum thyroid antibodies were elevated in 24.7%. Abnormalities were found in 39.5% of cMRIs and in 34.3% of EEGs. The main finding of our study was the high prevalence of CSF and autoantibody abnormalities in 54.4% of psychotic patients. In combination with cMRIs and EEGs, 75.6% showed abnormal findings. Our results are discussed with regard to the concept of immunological encephalopathy. Future studies should analyze the efficacy of immunomodulatory therapies. (shrink)

The problem of defining the self has traditionally been conceived as a task for philosophers. However, the development of immunology in the second part of the 20th century has led many scientists to conclude that immunology is the science of the self. This led to two different approaches to biological individuality: physiological individuation that is mostly concerned with organisms seen as strongly cohesive and unified metabolic entities, and evolutionary individuation where evolution by natural selection is seen as the (...) best framework for individuating biological entities. I discuss physiological approaches to biological individuation with a special focus on the immunological theories of the self. I argue that the immunological theories can only function as vague metaphors that do not provide a valid criterion for individuating organisms in biology. (shrink)

Immunology is central to contemporary biology and medicine, but it also provides novel philosophical insights. Its most significant contribution to philosophy concerns the understanding of biological individuality: what a biological individual is, what makes it unique, how its boundaries are established and what ensures its identity through time. Immunology also offers answers to some of the most interesting philosophical questions. What is the definition of life? How are bodily systems delineated? How do the mind and the body interact? (...) In this Element, Thomas Pradeu considers the ways in which immunology can shed light on these and other important philosophical issues. This title is also available as Open Access on Cambridge Core. (shrink)

Immunology is a notoriously complex field with distinct concepts and terminology. Yet immunologists regularly and effectively collaborate with other researchers, notably clinicians and experts in population health. How does such ‘collaboration without convergence’ work? This paper offers an answer. Immunology exhibits three features that support collaboration in the absence of major consensus on theories, methods, or concepts. These are: a multifaceted target of inquiry, therapeutic aspirations, and a clear interdisciplinary pathway. Building on these features, I sketch a general (...) account of “low-effort interdisciplinarity” and connect this result to recent work on population health. (shrink)

Contemporary immunology has established its fundamental theory as a biological expression of personal identity, wherein the "immune self" is defended by the immune system. Protection of this agent putatively requires a cognitive capacity by which the self and the foreign are perceived and thereby discriminated; from such information, discernment of the environment is achieved and activation of pathways leading to an immune response may be initiated. This so-called cognitive paradigm embeds such functions as "perception," "recognition," "learning," and "memory" to (...) characterize immune processes, but the conceptual character of such functions has meanings that vary with the particular theory adopted. When different formulations of cognition are considered, immunology's conceptual infrastructure shifts: Extensions of conventional psychological understanding of representational cognition based on a subject-object dichotomy support notions of immune agency; alternatively, formulations of perception that dispense with representations and attendant notions of agency reconfigure the predicate epistemology dominating current immune theory. Reviewing immunological literature of the past five decades, these two understandings of perception – representational and non-representational – offer competing views of immune cognitive functions. These, in turn, provide competing philosophical understandings of immunology's conceptual foundations, which reflect parallel controversies dominating current debates in philosophy of mind and attendant discussions about personal identity. (shrink)

Observations suggesting the existence of natural antibody prior to exposure of an organism to the corresponding antigen, led to the natural selection theory of antibody formation of Jerne in 1955, and to the two signal hypothesis of Forsdyke in 1968. Aspects of these were not only first discoveries but also foundational discoveries in that they influenced contemporaries in a manner that, from our present vantage point, appears to have been constructive. Jerne’s later hypothesis (1971, European Journal of Immunology 1: (...) 1–9), that antibody-like receptors on lymphocytes were selected over evolutionary time for reactivity with the major histocompatibility complex (MHC) antigens of the species, was a first, but it was incorrect, and was foundational only to the extent that it emphasized the need to explain the Simonsen phenomenon. Although easily construed as derivative of Jerne (1971), the affinity/avidity model of Forsdyke (1975, Journal of Theoretical Biology 52: 187–198), which predicted that cell-surface components, including MHC antigens, would restrict antigen-reactivity by somatically shaping lymphocyte repertoires, was actually an extension of the two signal hypothesis. While presenting a mechanism for the positive selection of lymphocyte repertoires, and explaining the Simonsen phenomenon, the affinity/avidity model was not foundational in that it had to be independently rediscovered. For science to advance optimally we must seek to close temporal gaps so that first discoveries are also foundational. Listening to young scientists may be part of the solution. (shrink)

Philosophy of immunology is a subfield of philosophy of biology dealing with ontological and epistemological issues related to the studies of the immune system. While speculative investigations and abstract analyses have always been part of immune theorizing, until recently philosophers have largely ignored immunology. Yet the implications for understanding the philosophical basis of organismal functions framed by immunity offer new perspectives on fundamental questions of biology and medicine. Developed in the context of history of medicine, theoretical biology, and (...) medical anthropology, philosophy of immunology differs from these related branches of study in its focus on traditional philosophical questions concerning identity, individuality, ecology, cognition, scientific methodology and theory construction. This broad agenda derives from immunology’s multifaceted research program that has developed from its initial clinical challenges of host defense, transplantation, autoimmunity, tumor immunology, and allergy. In addition to these well-established research areas, immunity is now understood to play a central role in other physiological functions, development, ecology, and evolutionary mechanics. Holding together these diverse domains of inquiry lie philosophical commitments oriented by organismal identity. In this regard, pertinent issues are raised concerning cognition (organization of immune perception and information processing), the character of individuality (framed by the ecological context of immune-mediated assimilation and rejection), and the dynamics of complex systems (understood as holistic systems biology). Indeed, immunology, in the context of cognitive science, evolutionary biology, environmental sciences, and development provides multi-focal perspectives for philosophy of science. (shrink)

Immunity against SARS‐CoV‐2 that is acquired by convalescent COVID‐19 patients is examined in reference to (A) the Th17 cell generation system in psoriatic epidermis and (B) a recently discovered phenomenon in which Th17 cells are converted into tissue‐resident memory T (TRM) cells with Th1 phenotype. Neutrophils that are attracted to the site of infection secrete IL‐17A, which stimulates lung epithelial cells to express CCL20. Natural Th17 (nTh17) cells are recruited to the infection site by CCL20 and expand in the presence (...) of IL‐23. These nTh17 cells are converted to TRM cells upon encounter with SARS‐CoV‐2 and continue to exist as ex‐Th17 cells, which exert Th1‐like immunity during a memory response. G‐CSF can induce nTh17 cell accumulation at the infection site because it promotes neutrophil egress from the bone marrow. Hence, G‐CSF may be effective against COVID‐19. Administration of G‐CSF to patients infected with SARS‐CoV‐2 is worth a clinical trial. (shrink)

Studies on music in the area of cognitive sciences – quite varied despite their short history – meet with scepticism. The author of this introduction, presenting some spectacular examples of research on musical improvisation, tries to demonstrate that they enrich rather than reduce our understanding of this phenomenon.

In this fascinating and inventive work, A. David Napier argues that the central assumption of immunology—that we survive through the recognition and elimination of non-self—has become a defining concept of the modern age. Tracing this immunological understanding of self and other through an incredibly diverse array of venues, from medical research to legal and military strategies and the electronic revolution, Napier shows how this defensive way of looking at the world not only destroys diversity but also eliminates the possibility (...) of truly engaging difference, thereby impoverishing our culture and foreclosing tremendous opportunities for personal growth. To illustrate these destructive consequences, Napier likens the current craze for embracing diversity and the use of politically correct speech to a cultural potluck to which we each bring different dishes, but at which no one can eat unless they abide by the same rules. Similarly, loaning money to developing nations serves as a tool both to make the peoples in those nations more like us and to maintain them in the nonthreatening status of distant dependents. To break free of the resulting downward spiral of homogenization and self-focus, Napier suggests that we instead adopt a new defining concept based on embryology, in which development and self-growth take place through a process of incorporation and transformation. In this effort he suggests that we have much to learn from non-Western peoples, such as the Balinese, whose ritual practices require them to take on the considerable risk of injecting into their selves the potential dangers of otherness—and in so doing ultimately strengthen themselves as well as their society. _The Age of Immunology,_ with its combination of philosophy, history, and cultural inquiry, will be seen as a manifesto for a new age and a new way of thinking about the world and our place in it. (shrink)

In his publications since the three-volume Spheres project, Peter Sloterdijk thematizes religion as a now outmoded immunological system. He says it can no longer perform its historical function because humans have lost the protection of a world periphery. The entirety of what was “outside” is now “inside,” and this has happened because: (1) spheres are systems, and as Luhmann shows, systems naturally complexify and expand themselves by becoming self-reflective; and (2), as Nietzsche says, humans are driven by a need to (...) surpass themselves. The loss of world periphery is manifest in the climate crisis, which registers as a general sense that we must “change our lives.” This gives Sloterdijk the chance (or so I argue) to create a new sphere (in the symbolic mode) that can be shared by all humans, a function no so-called world religion can fulfill. This new solidarity would come about when the earth becomes the completing “other” to every self, and individuals act in accordance with the imperative to assure the existence of human life on earth. The last section of the paper contrasts Sloterdijk’s spherology with Latour’s actor–network theory, and his later move into political ecology. I argue that, despite their alliance against “globalism,” Latour and Sloterdijk are working with very different models of space (spheres vs. networks) and have different agendas vis-à-vis the climate crisis. Sloterdijk is trying to build ethical solidarity among humans, while Latour is concerned with a politics (in the Schmittian sense) between both human and nonhuman actors, including Gaia, which is both the space of action (a network of networks) and an actor in its own right. And finally, I take up Sloterdijk’s statement that religions were never anything other than human practices, compared with Latour’s call for acting “religiously,” which means “respecting what others cling to.” I do this by way of showing there are conceptual limitations to the concept of spheres and to Sloterdijk’s project overall. (shrink)

The question “What is an organism?”, formerly considered as essential in biology, has now been increasingly replaced by a larger question, “What is a biological individual?”. On the grounds that i) individuation is theory-dependent, and ii) physiology does not offer a theory, biologists and philosophers of biology have claimed that it is the theory of evolution by natural selection which tells us what counts as a biological individual. Here I show that one physiological field, immunology, offers a theory, which (...) makes possible a biological individuation based on physiological grounds. I give a new answer to the question of the individuation of an organism by linking together the evolutionary and the immunological approaches to biological individuation. (shrink)

Context: Immunity includes cognitive concepts: the organism is thought to specifically recognize foreign materials and develop a memory of these encounters. Vaccines are thought to work by enhancing this immunological memory. Lymphocytes are key cells and specific antibodies are key molecules in immune recognition. Antibodies are blood proteins called “immunoglobulins.” Spontaneously formed immunoglobulins are seen as “natural” antibodies to dietary components and commensal bacteria. Immune cognition is used simply as a didactic metaphor. Problem: Do the cognitive aspects of immunology (...) stem from the activities of cells and molecules, or are they ascribed by the immunologist operating as a human observer? (1) An immense variety of immunoglobulins may bind to the same antigen with different binding energies. It is the immunologist who arbitrates the boundary between those that are specific (and declared antibodies) and those that are not. Specific antibodies serve as functional labels pasted onto natural immunoglobulins, as if they were recognizing elements. Is this “arbitration” the true cognitive event ascribed to immunoglobulins and lymphocytes? (2) A major impasse exists between progress in experimental immunology and its translation into clinical results. A proper understanding of immunological activity demands a wider view of an organism’s biology and, also, of the interference of human observers in delineating experimental realities, such as the specificity of immune recognition. Maturana’s biology of cognition and language provides one such approach. Method: Use of Maturana’s biology of cognition and language concepts to describe immunological activity. Results: A whole new understanding of immunological activity is suggested. Implications: A major change in the way of seeing is proposed that may eventually help the translation of this knowledge into clinical results. Furthermore, the immune system may also become a proper model for cognitive analyses. (shrink)

This groundbreaking book brings together the latest discoveries about the immune system in both Eastern and Western medicine to show how a balanced system can help strengthen the body.

The Limits of the Self, will be essential reading for anyone interested in the definition of biological individuality and the understanding of the immune system.

Anuran amphibian metamorphosis is an immunologically interesting period. For the investigator, it provides an unusual opportunity for analyzing both humoral regulation of the immune response and the development and maintenance of self‐tolerance. Some of the questions one can ask are: Why don't immunocompetent larvae destroy antigenically disparate adult cells as they differentiate within them during metamorphosis? Do the dramatic hormonal changes occurring during this period regulate immunological function? How do animals in metamophorsis protect themselves from their immunologically hostile environment?

Authors frequently refer to gene-based selection in biological evolution, the reaction of the immune system to antigens, and operant learning as exemplifying selection processes in the same sense of this term. However, as obvious as this claim may seem on the surface, setting out an account of “selection” that is general enough to incorporate all three of these processes without becoming so general as to be vacuous is far from easy. In this target article, we set out such a general (...) account of selection to see how well it accommodates these very different sorts of selection. The three fundamental elements of this account are replication, variation, and environmental interaction. For selection to occur, these three processes must be related in a very specific way. In particular, replication must alternate with environmental interaction so that any changes that occur in replication are passed on differentially because of environmental interaction. One of the main differences among the three sorts of selection that we investigate concerns the role of organisms. In traditional biological evolution, organisms play a central role with respect to environmental interaction. Although environmental interaction can occur at other levels of the organizational hierarchy, organisms are the primary focus of environmental interaction. In the functioning of the immune system, organisms function as containers. The interactions that result in selection of antibodies during a lifetime are between entities (antibodies and antigens) contained within the organism. Resulting changes in the immune system of one organism are not passed on to later organisms. Nor are changes in operant behavior resulting from behavioral selection passed on to later organisms. But operant behavior is not contained in the organism because most of the interactions that lead to differential replication include parts of the world outside the organism. Changes in the organism's nervous system are the effects of those interactions. The role of genes also varies in these three systems. Biological evolution is gene-based (i.e., genes are the primary replicators). Genes play very different roles in operant behavior and the immune system. However, in all three systems, iteration is central. All three selection processes are also incredibly wasteful and inefficient. They can generate complexity and novelty primarily because they are so wasteful and inefficient. Key Words: evolution; immunology; interaction; operant behavior; operant learning; replication; selection; variation. (shrink)

Observations suggesting the existence of natural antibody prior to exposure of an organism to the corresponding antigen, led to the natural selection theory of antibody formation of Jerne in 1955, and to the two signal hypothesis of Forsdyke in 1968. Aspects of these were not only first discoveries but also foundational discoveries in that they influenced contemporaries in a manner that, from our present vantage point, appears to have been constructive. Jerne's later hypothesis (1971, European Journal of Immunology 1: (...) 1-9), that antibody-like receptors on lymphocytes were selected over evolutionary time for reactivity with the major histocompatibility complex (MHC) antigens of the species, was a first, but it was incorrect, and was foundational only to the extent that it emphasized the need to explain the Simonsen phenomenon. Although easily construed as derivative of Jerne (1971), the affinity/avidity model of Forsdyke (1975, Journal of Theoretical Biology 52: 187-198), which predicted that cell-surface components, including MHC antigens, would restrict antigen-reactivity by somatically shaping lymphocyte repertoires, was actually an extension of the two signal hypothesis. While presenting a mechanism for the positive selection of lymphocyte repertoires, and explaining the Simonsen phenomenon, the affinity/avidity model was not foundational in that it had to be independently rediscovered. For science to advance optimally we must seek to close temporal gaps so that first discoveries are also foundational. Listening to young scientists may be part of the solution. (shrink)

During the 1940s and 1950s, the Australian microbiologist F. Macfarlane Burnet sought a biologically plausible explanation of antibody production. In this essay, we seek to recover the conceptual pathways that Burnet followed in his immunological theorizing. In so doing, we emphasize the influence of speculations on individuality, especially those of philosopher Alfred North Whitehead; the impact of cybernetics and information theory; and the contributions of clinical research into autoimmune disease that took place in Melbourne. We point to the influence of (...) local experimental and intellectual currents on Burnet’s work. Accordingly, this essay describes an arc distinct from most other tracings of Burnet’s conceptual development, which focus on his early bacteriophage research, his fascination with the work of Julian Huxley and other biologists in the 1920s, and his interest in North Atlantic experimental investigations in the life sciences. No doubt these too were potent influences, but they seem insufficient to explain, for example, Burnet’s sudden enthusiasm in the 1940s for immunological definitions of self and not-self. We want to demonstrate here how Burnet’s deep involvement in philosophical biology – along with attention to local clinical research – provided him with additional theoretic tools and conceptual equipment, with which to explain immune function. (shrink)

Taking up the body turn in sociology, this paper discusses scientific practices as embodied action from the perspective of Husserl’s phenomenological theory of the “Body”. Based on ethnographic data on a biology laboratory it will discuss the importance of the scientist’s Body for the performance of scientific activities. Successful researchers have to be skilled workers using their embodied knowledge for the process of tinkering towards the material transformation of their objects for data production. The researcher’s body then is an instrument (...) of measuring as well as a kind of archive of knowing. Their body becomes a disciplined instrument which has its own place and function inside the laboratory. Furthermore, the appresentational apperception of Bodies (Husserl) is being discussed as a basis for the emotional and ethical concerns towards laboratory-animals. Attitudes towards animals in the laboratory setting (as well as elsewhere) are highly emotional. Nevertheless, following the literature of the sociology of the body, those emotional reactions still follow certain cultural patterns which themselves can be understood as embodied ways of knowing “right” or “wrong”. Besides as an instrument, the scientist’s body can also be understood as a resource of emotional attachment towards animals. It is an instrument for performing transformation as well as one for caring. (shrink)

The self/non-self model, first proposed by F.M. Burnet, has dominated immunology for 60 years now. According to this model, any foreign element will trigger an immune reaction in an organism, whereas endogenous elements will not, in normal circumstances, induce an immune reaction. In this paper we show that the self/non-self model is no longer an appropriate explanation of experimental data in immunology, and that this inadequacy may be rooted in an excessively strong metaphysical conception of biological identity. We (...) suggest that another hypothesis, one based on the notion of continuity, gives a better account of immune phenomena. Finally, we underscore the mapping between this metaphysical deflation from self to continuity in immunology and the philosophical debate between substantialism and empiricism about identity. (shrink)

Immunology researchers are beginning to explore the possibilities of reproducibility, reuse and secondary analyses of immunology data. Open-access datasets are being applied in the validation of the methods used in the original studies, leveraging studies for meta-analysis, or generating new hypotheses. To promote these goals, the ImmPort data repository was created for the broader research community to explore the wide spectrum of clinical and basic research data and associated findings. The ImmPort ecosystem consists of four components–Private Data, Shared (...) Data, Data Analysis, and Resources—for data archiving, dissemination, analyses, and reuse. To date, more than 300 studies have been made freely available through the ImmPort Shared Data portal , which allows research data to be repurposed to accelerate the translation of new insights into discoveries. (shrink)

We analyse the effect of the regulatory T cells (Tregs) in the local control of the immune responses by T cells. We obtain an explicit formula for the level of antigenic stimulation of T cells as a function of the concentration of T cells and the parameters of the model. The relation between the concentration of the T cells and the antigenic stimulation of T cells is an hysteresis, that is unfold for some parameter values. We study the appearance of (...) autoimmunity from cross-reactivity between a pathogen and a self antigen or from bystander proliferation. We also study an asymmetry in the death rates. With this asymmetry we show that the antigenic stimulation of the Tregs is able to control locally the population size of Tregs. Other effects of this asymmetry are a faster immune response and an improvement in the simulations of the bystander proliferation. The rate of variation of the levels of antigenic stimulation determines if the outcome is an immune response or if Tregs are able to maintain control due to the presence of a transcritical bifurcation for some tuning between the antigenic stimuli of T cells and Tregs. This behavior is explained by the presence of a transcritical bifurcation. (shrink)

Disgust is reasoned to operate in conjunction with the immune system to help protect the body from illness. However, less is known about the factors that impact the degree to which individuals invest in pathogen avoidance (disgust) versus pathogen management (prophylactic immunological activity). Here, we examine the role that one’s control over pathogen contact plays in resolving such investment trade-offs, predicting that (a) those from low control environments will invest less in pathogen-avoidance strategies and (b) investment in each of these (...) two strategies will occur in a compensatory fashion (i.e. they will be traded off with one other). Across four studies, we found support for these predictions, using a variety of manipulations and measures. By providing novel insights into how one’s control over pathogen exposure influences disgust sensitivity and immune system activity, the current research poses an important contribution to the literature on disgust, pathogen avoidance, and the immune system. (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)

Thomas Pradeu’s The Limits of the Self provides a precise account of biological identity developed from the central concepts of immunology. Yet the central concepts most relevant to this task are themselves deemed inadequate, suffering from ambiguity and imprecision. Pradeu seeks to remedy this by proposing a new guiding theory for immunology, the continuity theory. From this, an account of biological identity is provided in terms of uniqueness and individuality, ultimately leading to a defense of the heterogeneous organism (...) as expressing the highest degree of individuality. (shrink)

This two-part article examines the competition between the clonal selection theory and the instructive theory of the immune response from 1957–1967. In Part I the concept of a temporally extended theory is introduced, which requires attention to the hitherto largely ignored issue of theory individuation. Factors which influence the acceptability of such an extended theory at different temporal points are also embedded in a Bayesian framework, which is shown to provide a rational account of belief change in science. In Part (...) II these factors, as elaborated in the Bayesian framework, are applied to the case of the success of the clonal selection theory and the failure of the instructive theory. (shrink)

This two-part article examines the competition between the clonal selection theory and the instructive theory of the immune response from 1957–1967. In Part I the concept of a temporally extended theory is introduced, which requires attention to the hitherto largely ignored issue of theory individuation. Factors which influence the acceptability of such an extended theory at different temporal points are also embedded in a Bayesian framework, which is shown to provide a rational account of belief change in science. In Part (...) II these factors, as elaborated in the Bayesian framework, are applied to the case of the success of the clonal selection theory and the failure of the instructive theory. (shrink)

Much was accomplished in the last decade in understanding how the adaptive immune system evolved to combat pathogens. Essential features of antigen presentation and T lymphocyte recognition were decipherd, setting the stage for further studies that elucidated basic elements of lymphocyte differentiation (including positive and negative selection during lymphocyte ontogeny) and the major interactions that occur among cells in secondary lymphoid organs in an ongoing immune response. The major challenges of today are found in the burgeoning fields of programmed cells (...) death, enzymology of recombination and somatic mutation, development of memory, and the recognition of pathogens by unconventional lymphocytes. (shrink)