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.

Scientific and philosophical accounts of cognition and perception have traditionally focused on the brain and external sense organs. The extended view of embodied cognition suggests including other parts of the body in these processes. However, one organ has often been overlooked: the gut. Frequently conceptualized as merely a tube for digesting food, there is much more to the gut than meets the eye. Having its own enteric nervous system, sometimes referred to as the “second brain,” the gut is also an immune organ and has a large surface area interacting with gut microbiota. The gut has been shown to play an important role in many physiological processes, and may arguably do so as well in perception and cognition. We argue that proposals of embodied perception and cognition should take into account the role of the “gut complex,” which considers the enteric nervous, endocrine, immune, and microbiota systems as well as gut tissue and mucosal structures. The gut complex is an interface between bodily tissues and the “internalized external environment” of the gut lumen, involved in many aspects of organismic activity beyond food intake. We thus extend current embodiment theories and suggest a more inclusive account of how to “mind the gut” in studying cognitive processes.

Reactive oxygen species (ROS) that exceed the antioxidative capacity of the cell can be harmful and are termed oxidative stress. Increasing evidence suggests that ROS are not exclusively detrimental, but can fulfill important signaling functions. Recently, we have been able to demonstrate that a NADPH oxidase-like enzyme (termed Yno1p) exists in the single-celled organism Saccharomyces cerevisiae. This enzyme resides in the peripheral and perinuclear endoplasmic reticulum and functions in close proximity to the plasma membrane. Its product, hydrogen peroxide, which is also produced by the action of the superoxide dismutase, Sod1p, influences signaling of key regulatory proteins Ras2p and Yck1p/2p. In the present work, we demonstrate that Yno1p-derived H₂O₂ regulates outputs controlled by three MAP kinase pathways that can share components: the filamentous growth (filamentous growth MAPK (fMAPK)), pheromone response, and osmotic stress response (hyperosmolarity glycerol response, HOG) pathways. A key structural component and regulator in this process is the actin cytoskeleton. The nucleation and stabilization of actin are regulated by Yno1p. Cells lacking YNO1 showed reduced invasive growth, which could be reversed by stimulation of actin nucleation. Additionally, under osmotic stress, the vacuoles of a ∆yno1 strain show an enhanced fragmentation. During pheromone response induced by the addition of alpha-factor, Yno1p is responsible for a burst of ROS. Collectively, these results broaden the roles of ROS to encompass microbial differentiation responses and stress responses controlled by MAPK pathways.

How does microbiota research impact our understanding of biological individuality? We summarize the interdisciplinary summer school on “Microbiota, symbiosis and individuality: conceptual and philosophical issues” (July 2019), which was supported by a European Research Council starting grant project “Immunity, DEvelopment, and the Microbiota” (IDEM). The summer school centered around interdisciplinary group work on four facets of microbiota research: holobionts, individuality, causation, and human health. The conceptual discussion of cutting-edge empirical research provided new insights into microbiota and highlights the value of incorporating into meetings experts from other disciplines, such as philosophy and history of science.

A central question for immunology is: what does the immune system recognize and according to which principles does this kind of recognition work? Immunology has been dominated by the idea of recognizing molecular structures and triggering an appropriate immune response when facing non-self or danger. Recently, characterizations in terms of function have turned out to be more conserved and explanatory in microbiota research than taxonomic composition for understanding microbiota-host interactions. Starting from a conceptual analysis of the notions of structure and function, I raise the title question whether it is possible for the immune system to recognize microbial functions. I argue that this is indeed the case, making the claim that some function-associated molecular patterns are not indicative of the presence of certain taxa (''who is there'') but of biochemical activities and effects (''what is going on''). In addition, I discuss case studies which show that there are immunological sensors that can directly detect microbial activities, irrespective of their specific structural manifestation. At the same time, the discussed account puts the causal role notions of function on a more realist and objective basis.