Optimal evolutionary decision-making to store immune memory

Mapping Intimacies ◽

10.1101/2020.07.02.185223 ◽

2020 ◽

Author(s):

Oskar H Schnaack ◽

Armita Nourmohammad

Keyword(s):

Decision Making ◽

Immune System ◽

Cell Fate ◽

Adaptive Immune System ◽

Memory Formation ◽

Immune Memory ◽

Central Feature ◽

Cell Fate Decisions ◽

Adaptive Immune ◽

Immune Receptors

The adaptive immune system in vertebrates consists of highly diverse immune receptors to mount specific responses against a multitude of pathogens. A central feature of the adaptive immune system is the ability to form a memory to act more efficiently in future encounters with similar pathogens. However, memory formation especially in B-cells is one of the least understood cell fate decisions in the immune system. Here, we present a framework to characterize optimal strategies to store memory in order to maximize the utility of immune response to counter evolving pathogens throughout an organism’s lifetime. To do so, we have incorporated the kinetics and energetics of memory response as ingredients of non-equilibrium decision-making between an adaptive exploration to mount a specific and novel response or exploitation of existing memory that can be activated rapidly yet with a reduced specificity against evolved pathogens. To achieve a long-term benefit for the host, we show that memory generation should be actively regulated and dependent on immune receptors’ affinity, with a preference for cross-reactive receptors with a moderate affinity against pathogens as opposed to high affinity receptors— a recipe that is consistent with recent experimental findings [1, 2]. Moreover, we show that the specificity of memory should depend on the organism’s lifespan, and shorter-lived organisms with fewer pathogenic encounters throughout their lifetime should store more cross-reactive memory. Overall, our framework provides a baseline to gauge the efficacy of immune memory formation in light of an organism’s coevolutionary history with pathogens.

Download Full-text

Optimal evolutionary decision-making to store immune memory

eLife ◽

10.7554/elife.61346 ◽

2021 ◽

Vol 10 ◽

Author(s):

Oskar H Schnaack ◽

Armita Nourmohammad

Keyword(s):

Cell Fate ◽

Adaptive Immune System ◽

Optimal Strategies ◽

Cross Reactivity ◽

Immune Memory ◽

Mathematical Framework ◽

Effective Protection ◽

Cell Fate Decisions ◽

Adaptive Immune ◽

Coevolutionary History

The adaptive immune system provides a diverse set of molecules that can mount specific responses against a multitude of pathogens. Memory is a key feature of adaptive immunity, which allows organisms to respond more readily upon re-infections. However, differentiation of memory cells is still one of the least understood cell fate decisions. Here, we introduce a mathematical framework to characterize optimal strategies to store memory to maximize the utility of immune response over an organism's lifetime. We show that memory production should be actively regulated to balance between affinity and cross-reactivity of immune receptors for an effective protection against evolving pathogens. Moreover, we predict that specificity of memory should depend on the organism's lifespan, and shorter-lived organisms with fewer pathogenic encounters should store more cross-reactive memory. Our framework provides a baseline to gauge the efficacy of immune memory in light of an organism's coevolutionary history with pathogens.

Download Full-text

Experimental evolution of immunological specificity

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1904828116 ◽

2019 ◽

Vol 116 (41) ◽

pp. 20598-20604 ◽

Cited By ~ 9

Author(s):

Kevin Ferro ◽

Robert Peuß ◽

Wentao Yang ◽

Philip Rosenstiel ◽

Hinrich Schulenburg ◽

...

Keyword(s):

Immune System ◽

Adaptive Immune System ◽

High Specificity ◽

Immune Memory ◽

Transcriptomic Response ◽

Immune Priming ◽

Immune Genes ◽

Adaptive Immune ◽

Immunological Specificity ◽

Invertebrate Model

Memory and specificity are hallmarks of the adaptive immune system. Contrary to prior belief, innate immune systems can also provide forms of immune memory, such as immune priming in invertebrates and trained immunity in vertebrates. Immune priming can even be specific but differs remarkably in cellular and molecular functionality from the well-studied adaptive immune system of vertebrates. To date, it is unknown whether and how the level of specificity in immune priming can adapt during evolution in response to natural selection. We tested the evolution of priming specificity in an invertebrate model, the beetle Tribolium castaneum. Using controlled evolution experiments, we selected beetles for either specific or unspecific immune priming toward the bacteria Pseudomonas fluorescens, Lactococcus lactis, and 4 strains of the entomopathogen Bacillus thuringiensis. After 14 generations of host selection, specificity of priming was not universally higher in the lines selected for specificity, but rather depended on the bacterium used for priming and challenge. The insect pathogen B. thuringiensis induced the strongest priming effect. Differences between the evolved populations were mirrored in the transcriptomic response, revealing involvement of immune, metabolic, and transcription-modifying genes. Finally, we demonstrate that the induction strength of a set of differentially expressed immune genes predicts the survival probability of the evolved lines upon infection. We conclude that high specificity of immune priming can evolve rapidly for certain bacteria, most likely due to changes in the regulation of immune genes.

Download Full-text

Beyond lysis: how complement influences cell fate

Clinical Science ◽

10.1042/cs20020362 ◽

2003 ◽

Vol 104 (5) ◽

pp. 455-466 ◽

Cited By ~ 129

Author(s):

Duncan S. COLE ◽

B. Paul MORGAN

Keyword(s):

Immune System ◽

Cell Fate ◽

Cell Activation ◽

Membrane Attack Complex ◽

Adaptive Immune System ◽

Innate Immune ◽

Central Component ◽

Target Cells ◽

Membrane Pore ◽

Adaptive Immune

Complement is a central component of the innate immune system involved in protection against pathogens. For many years, complement has been known to cause death of targets, either indirectly by attracting and activating phagocytes or directly by formation of a membrane pore, the membrane attack complex. More recently, it has been recognized that complement may cause other ‘non-classical’ effects that may not directly be aimed at killing of pathogens. Products of complement activation collaborate with the adaptive immune system to enhance responses to antigens. The membrane attack complex of complement, apart from lysing cells, can also trigger diverse events in target cells that include cell activation, proliferation, resistance to subsequent complement attack and either resistance to, or induction of, apoptosis. Various complement products play important roles in signalling for clearance by phagocytes of apoptotic self cells. Here we review some of these non-classical activities of complement and stress the roles that they may play in maintaining the integrity of the organism.

Download Full-text

Adaptive Immune System in Fish

Turkish Journal of Fisheries and Aquatic Sciences ◽

10.4194/trjfas20235 ◽

2021 ◽

Vol 22 (4) ◽

Author(s):

Adef Othan Kordon ◽

Lesya Pinchuk ◽

Attila Karsi

Keyword(s):

T Cells ◽

Immune System ◽

Immune Responses ◽

Teleost Fish ◽

Cytotoxic T Cells ◽

Adaptive Immune System ◽

Immune Memory ◽

Cellular Cytotoxicity ◽

Th Cells ◽

Adaptive Immune

The immune system of all jawed vertebrates is composed of two major subsystems, the innate (non-specific) and adaptive (specific) immune system. The innate immune system is the first to respond to infectious agents; however, it does not provide longlasting protection. The adaptive immune system is activated later and responds to pathogens with specificity and memory. The main components of the adaptive immune system, including T cell receptors (TCRs), major histocompatibility complex (MHC), immunoglobulins (Igs), and recombination-activating gene (RAG) arose in the first jawed fish (cartilaginous and teleost fish). This review explores and discusses components of the adaptive immune system in teleost fish and recent developments in comparative immunology. Similar to mammals, the adaptive immune system in teleost fish is divided into two components: cellular-mediated responses and humoralmediated responses. T cells, the principal elements of cellular-mediated adaptive immune responses, differentiate into effector helper T (Th) cells or effector cytotoxic T cells (CTLs). The central elements involved in the differentiation of Th subsets in mammals, cytokines and master transcription factors, have also been identified in teleost fish. In addition, each subset of Th cells, defined with a particular cytokine to control the immune responses, has been described in teleost fish. Similarly, to mammals, CTLs contribute to cellular cytotoxicity in teleost fish. B cells act as a central player in humoral-mediated adaptive immunity by producing opsonizing, neutralizing and complement-binding antibodies and inducing antibody-dependent cellular cytotoxicity (ADCC). Three classes of antibodies named IgM, IgD, and IgT/Z have been characterized in teleost fish. The presence of an adaptive immune system and consequent immune memory in teleost fish allows vaccination, the most appropriate method for disease control in aquaculture. Immunological studies in fish provide a comprehensive assessment of the fish immune system, which is crucial for understanding the evolution of the mammalian immune system.

Download Full-text

DAMPs and Innate Immune Training

Frontiers in Immunology ◽

10.3389/fimmu.2021.699563 ◽

2021 ◽

Vol 12 ◽

Author(s):

Elisa Jentho ◽

Sebastian Weis

Keyword(s):

Immune System ◽

Adaptive Immune System ◽

Innate Immune ◽

Immune Memory ◽

Trained Immunity ◽

Downstream Signaling ◽

Adaptive Immune ◽

Open Questions ◽

Molecular Patterns ◽

Damage Associated Molecular Patterns

The ability to remember a previous encounter with pathogens was long thought to be a key feature of the adaptive immune system enabling the host to mount a faster, more specific and more effective immune response upon the reencounter, reducing the severity of infectious diseases. Over the last 15 years, an increasing amount of evidence has accumulated showing that the innate immune system also has features of a memory. In contrast to the memory of adaptive immunity, innate immune memory is mediated by restructuration of the active chromatin landscape and imprinted by persisting adaptations of myelopoiesis. While originally described to occur in response to pathogen-associated molecular patterns, recent data indicate that host-derived damage-associated molecular patterns, i.e. alarmins, can also induce an innate immune memory. Potentially this is mediated by the same pattern recognition receptors and downstream signaling transduction pathways responsible for pathogen-associated innate immune training. Here, we summarize the available experimental data underlying innate immune memory in response to damage-associated molecular patterns. Further, we expound that trained immunity is a general component of innate immunity and outline several open questions for the rising field of pathogen-independent trained immunity.

Download Full-text

Functions of the immune system

10.1093/med/9780199568741.003.0293 ◽

2018 ◽

Author(s):

Malini Bhole

Keyword(s):

Immune System ◽

Adaptive Immune System ◽

Innate Immune ◽

Central Feature ◽

Humoral Factors ◽

Adaptive Immune ◽

System P ◽

The Common ◽

Physical And Chemical ◽

Adaptive Immune Systems

This chapter reviews the functions of the immune system, which has evolved to provide a defence mechanism against microbial challenges, and is divided into two main branches, innate and adaptive. In addition, there are physical and chemical barriers, including skin, mucous membrane, mucous secretions, saliva, and various enzymes, and these contribute to the first line of defence against pathogens. The innate immune system provides the initial quick response for rapid recognition and elimination of pathogens, as opposed to the adaptive immune system, which has evolved to provide a more definitive and finely tuned response. The common central feature of both of these systems is the ability to distinguish between self and non-self. The recognition of non-self or ‘foreign’ pathogens and the subsequent immune response is orchestrated by a whole range of cells and soluble (humoral) factors in both innate and adaptive immune systems.

Download Full-text