Exploration of immune systems in prokaryotes, such as restriction‐modification or CRISPR‐Cas, shows that both innate and adaptive systems possess programmed cell death (PCD) potential. The key outstanding question is how the immune systems sense and “predict” infection outcomes to “decide” whether to fight the pathogen or induce PCD. There is a striking parallel between this life‐or‐death decision faced by the cell and the decision by temperate viruses to protect or kill their hosts, epitomized by the lysis‐lysogeny switch of bacteriophage Lambda. (...) Immune systems and temperate phages sense the same molecular inputs, primarily, DNA damage, that determine whether the cell lives or dies. Because temperate (pro)phages are themselves components of prokaryotic genomes, their shared “interests” with the hosts result in coregulation of the lysis‐lysogeny switch and immune systems that jointly provide the cell with the decision machinery to probe and predict infection outcomes, answering the life‐or‐death question. (shrink)

The CRISPR-Cas systems of bacterial and archaeal adaptive immunity have become a household name among biologists and even the general public thanks to the unprecedented success of the new generation of genome editing tools utilizing Cas proteins. However, the fundamental biological features of CRISPR-Cas are of no lesser interest and have major impacts on our understanding of the evolution of antivirus defense, host-parasite coevolution, self versus non-self discrimination and mechanisms of adaptation. CRISPR-Cas systems present the best known case in point (...) for Lamarckian evolution, i.e. generation of heritable, adaptive genomic changes in response to encounters with external factors, in this case, foreign nucleic acids. CRISPR-Cas systems employ multiple mechanisms of self versus non-self discrimination but, as is the case with immune systems in general, are nevertheless costly because autoimmunity cannot be eliminated completely. In addition to the autoimmunity, the fitness cost of CRISPR-Cas systems appears to be determined by their inhibitory effect on horizontal gene transfer, curtailing evolutionary innovation. Hence the dynamic evolution of CRISPR-Cas loci that are frequently lost and acquired by archaea and bacteria. Another fundamental biological feature of CRISPR-Cas is its intimate connection with programmed cell death and dormancy induction in microbes. In this and, possibly, other immune systems, active immune response appears to be coupled to a different form of defense, namely, “altruistic” shutdown of cellular functions resulting in protection of neighboring cells. Finally, analysis of the evolutionary connections of Cas proteins reveals multiple contributions of mobile genetic elements to the origin of various components of CRISPR-Cas systems, furthermore, different biological systems that function by genome manipulation appear to have evolved convergently from unrelated MGE. The shared features of adaptive defense systems and MGE, namely the ability to recognize and cleave unique sites in genomes, make them ideal candidates for genome editing and engineering tools. (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 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)

All surviving jawed vertebrate representatives achieve diversity in immunoglobulin‐based B and T cell receptors for antigen recognition through recombinatorial rearrangement of V(D)J segments. However, the extant jawless vertebrates, lampreys and hagfish, instead generate three types of variable lymphocyte receptors (VLRs) through a template‐mediated combinatorial assembly of different leucine‐rich repeat (LRR) sequences. The clonally diverse VLRB receptors are expressed by B‐like lymphocytes, while the VLRA and VLRC receptors are expressed by lymphocyte lineages that resemble αβ and γδ T lymphocytes, respectively. These (...) findings suggest that three basic types of lymphocytes, one B‐like and two T‐like, are an essential feature of vertebrate adaptive immunity. Around 500 million years ago, a common ancestor of jawed and jawless vertebrates evolved a genetic program for the development of prototypic lymphoid cells as a foundation for an adaptive immune system. This acquisition preceded the convergent evolution of alternative types of clonally diverse receptors for antigens in all vertebrates, as reviewed in this article. (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)

All living organisms are under stress imposed by their surrounding environments. They must adapt to their stressors to live and survive. At the forefront of this adaptation is a defense system called immunity. Immunity, as the most ancient cognitive apparatus with memory function, is present in all living organisms. In previous reports, minimal cognitive function was defined as a “biologized” concept—namely, perception of elements in a milieu, integration of perceived information, reaction according to integrated information, and memory of that experience. (...) In this study, I aim to explore the essential feature of immunity by synthesizing scientific facts and “metaphysicalizing” them with logical reasoning. As a result of my analysis, I have realized the essential element in immunity: the capacity to preserve the existence of organisms by regulating their physiology and pathology. Having further analyzed immunity with special reference to the philosophy of Baruch Spinoza and George Canguilhem, _conatus_ (“appetite”, to be precise) with normative activities is deeply embedded in immunity and may constitute its essential feature. Given that _conatus_ and normativity imply mental elements, including the judgment of good and bad or health and disease, it is possible to conclude that the essential function of immunity includes cognition with normative connotations. This inclusive view encourages us to rethink the fundamental nature and philosophical implications of immunity from the cognitive perspective. (shrink)