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Invertebrates are the protagonists of a recent paradigm shift because they now show that vertebrates are not the only group with immune memory. This review discusses the concept of immune priming, its characteristics, and differences with trained immunity and immune enhancement. We include an update of the current status of immune priming within generations in different groups of invertebrates which now include work in 5 Phyla: Ctenophora, Cnidaria, Mollusca, Nematoda, and Arthropoda. Clearly, few Phyla have been studied. We also resume and discuss the effector mechanism related to immune memory, including integrating viral elements into the genome, endoreplication, and epigenetics. The roles of other elements are incorporated, such as hemocytes, immune pathways, and metabolisms. We conclude that taking care of the experimental procedure will discern if results provide or do not support the invertebrates' immune memory and that regarding mechanisms, indeed, there are no studies on the immune memory mechanisms, this is how specificity is reached, and how and where the immune memory is stored and how is recall upon subsequent encounters. Finally, we discuss the possibility of having more than one mechanism working in different groups of invertebrates depending on the environmental conditions.

Beetles are the most diverse group of insects in Insecta which can be found in almost every habitat and environment on Earth. The possessing of the rapid and effective immune defenses is one of the important factors for their success. It is generally recognized that beetles only rely on the non-specific innate immune defense, without immunological memory, to fight against pathogens. However, there was cumulative evidence for the innate immune memory in invertebrates, including beetles, over the last decades, implying that insect innate immunity is more complex and has more features than previously thought. In beetles, it has been well documented that the specific or nonspecific enhanced immunocompetence can persist throughout development within generations and can even be transferred to the descendents in the next generation. Although insect immune priming might be shaped by epigenetic modifications and transferring effectors, mRNA and microbial signals, the solid experimental evidence to support the causal relationship between any of them and immune priming is still scarce. The combined usage of 'omics' approaches and CRISPR/Cas9 in the appropriate insect models with well-known genetic background, Tribolium castaneum and Tenebrio molitor, will help us to decipher the molecular mechanisms by which immune priming occurs in beetles in depth.

Immune function varies with an animal’s endocrine physiology and energy reserves, as well as its abiotic and biotic environment. This context-dependency is thought to relate to adaptive trade-off resolution that varies from one context to the next; however, it is less clear how state- and environmentally-dependent differences in endocrine-immune signaling relate to survival in natural populations. We begin to address this question in a prospective study on a free-living passerine bird, the tree swallow (Tachycineta bicolor), by capitalizing upon naturally-occurring variation in ectoparasitism in 12-day old chicks. We measured body mass, hematological gene expression of the pro-inflammatory cytokine interleukin-6 (IL-6) as well as corticosterone (CORT) secretion at baseline and in response to 30 min of handling. We found that chicks with ectoparasites had smaller body mass and higher levels of IL-6 gene expression at this critical stage of post-natal growth and development. Mass and IL-6 were positively correlated, but only among parasitized chicks, suggesting that larger chicks mount stronger immune responses when necessary, i.e. in the presence of ectoparasites that are known to induce inflammation. IL-6 mRNA expression was negatively correlated with stress-induced CORT levels, suggesting that this proxy of inflammation may be co-regulated with or coordinated by glucocorticoids. More importantly, these endocrine-immune parameters predicted survival to fledging, which was positively associated with IL-6 mRNA abundance and, to a lesser degree, CORT reactivity. These results suggest a link between endocrine-immune interactions and performance in nature, and as a consequence, they shed light on the potentially adaptive, context-dependent interplay between body mass, immunity, and endocrine physiology during development.

The vertebrate innate immune system provides hosts with a rapid, non-specific response to a wide range of invading pathogens. However, the speed and duration of innate responses will be influenced by the co-evolutionary dynamics of specific host-pathogen combinations. Here, we show that low pathogenic avian influenza virus (LPAI) subtype H1N1 elicits a strong but extremely transient innate immune response in its main wildlife reservoir, the mallard (Anas platyrhynchos). Using a series of experimental and methodological improvements over previous studies, we followed the expression of retinoic acid inducible gene 1 (RIG-I) and myxovirus resistance gene (Mx) in mallards semi-naturally infected with low pathogenic H1N1. One day post infection, both RIG-I and Mx were significantly upregulated in all investigated tissues. By two days post infection, the expression of both genes had generally returned to basal levels, and remained so for the remainder of the experiment. This is despite the fact that birds continued to actively shed viral particles throughout the study period. We additionally show that the spleen plays a particularly active role in the innate immune response to LPAI. Waterfowl and avian influenza viruses have a long co-evolutionary history, suggesting that the mallard innate immune response has evolved to provide a minimum effective response to LPAIs such that the viral infection is brought under control while minimising the damaging effects of a sustained immune response.

The first-line effector mechanisms of immune defence, including inflammation and oxidative burst, contribute significantly to host-pathogen resistance. Whether these immune responses undergo age-related changes in birds remains unknown. Here, we tracked selected inflammatory parameters in 54 free-living great tits (Parus major) of known age, captured repeatedly over three consecutive years, with the aims to investigate long-term repeatability and age-dependent changes in cellular oxidative burst responsiveness upon in vitro stimulation with bacterial lipopolysaccharide (LPS), and to identify its relationships with leukotriene B4 (LTB4) levels and haematological traits. In addition, we linked these immunological traits to selected physiological markers (antioxidants and oxidative stress markers). LTB4 levels increased with age and we have shown a similar non-significant tendency also for absolute granulocyte counts, indicating propagating chronic inflammation over the bird's lifetime, consistent with the inflammaging hypothesis. In contrast, cellular oxidative burst followed a quadratic trend of dependency on age with a peak in midlife individuals, in line with the immunosenescence hypothesis. Interestingly, LTB4 levels were positively associated with general oxidative damage, but negatively with antioxidant glutathione peroxidase activity, indicating links to redox balance. This longitudinal study demonstrates the contrasting patterns of age-related changes in background and acute markers of pro-inflammatory immunity contributing to immunosenescence in birds and thus provides basis for interpretation of the tested inflammatory markers in cross-cohort datasets.

The classic biomedical view is that stress hormone effects on the immune system are largely pathological, especially if the stress is chronic. However, more recent interpretations have focused on the potential adaptive function of these effects. This paper examines stress response-immune system interactions from a physiological network perspective, using insects because of their simpler physiology. For example, stress hormones can reduce disease resistance, yet activating an immune response results in the release of stress hormones in both vertebrates and invertebrates. From a network perspective, this phenomenon is consistent with the 'sharing' of the energy-releasing ability of stress hormones by both the stress response and the immune system. Stress-induced immunosuppression is consistent with the stress response 'borrowing' molecular components from the immune system to increase the capacity of stress-relevant physiological processes (i.e. a trade off). The insect stress hormones octopamine and adipokinetic hormone can also 'reconfigure' the immune system to help compensate for the loss of some of the immune system's molecular resources (e.g. apolipophorin III). This view helps explain seemingly maladaptive interactions between the stress response and immune system. The adaptiveness of stress hormone effects on individual immune components may be apparent only from the perspective of the whole organism. These broad principles will apply to both vertebrates and invertebrates.

The spread of the invasive harlequin ladybird (Harmonia axyridis) in Europe is accompanied by the decline of the native and non-invasive two-spotted ladybird (Adalia bipunctata). Here we show that microsporidia carried by H. axyridis can kill A. bipunctata following the oral uptake of spores, suggesting that their horizontal transmission via intraguild predation may help the invader to outcompete its native competitor. The native seven-spotted ladybird (Coccinella septempunctata) is thought to be less susceptible both to the spread of H. axyridis and to its microsporidia. To investigate whether the distinct levels of pathogen susceptibility in these three ladybird species are determined by their immune systems, we compared the immunity-related transcriptomes of untreated beetles and beetles challenged with suspensions of bacteria and yeast. We found that H. axyridis carries three and four times as many genes encoding antimicrobial peptides representing the attacin, coleoptericin and defensin families than C. septempunctata and A. bipunctata, respectively. Gene expression studies following the injection of bacteria and yeasts into beetles revealed that members of these three antimicrobial peptide families are also induced more strongly in H. axyridis than C. septempunctata or A. bipunctata. Our results therefore support the hypothesis that a superior immune system promotes the performance of invasive species.

The widely-distributed North American species Peromyscus leucopus and P. maniculatus of cricetine rodents are, between them, important natural reservoirs for several zoonotic diseases of humans: Lyme disease, human granulocytic anaplasmosis, babesiosis, erhlichiosis, hard tickborne relapsing fever, Powassan virus encephalitis, hantavirus pulmonary syndrome, and plague. While these infections are frequently disabling and sometimes fatal for humans, the peromyscines display little pathology and apparently suffer few consequences, even when prevalence of persistent infection in a population is high. While these Peromyscus spp. are unable to clear some of the infections, they appear to have partial resistance, which limits the burden of the pathogen. In addition, they display traits of infection tolerance, which reduces the damage of the infection. Research on these complementary resistance and tolerance phenomena in Peromyscus has relevance both for disease control measures targeting natural reservoirs and for understanding the mechanisms of the comparatively greater sickness of many humans with these and other infections.

Multidirectional interactions among the immune, endocrine, and nervous systems have been demonstrated in humans and non-human animal models for many decades by the biomedical community, but ecological and evolutionary perspectives are lacking. Neuroendocrine-immune interactions can be conceptualized using a series of feedback loops, which culminate into distinct neuroendocrine-immune phenotypes. Behavior can exert profound influences on these phenotypes, which can in turn reciprocally modulate behavior. For example, the behavioral aspects of reproduction, including courtship, aggression, mate selection and parental behaviors can impinge upon neuroendocrine-immune interactions. One classic example is the immunocompetence handicap hypothesis (ICHH), which proposes that steroid hormones act as mediators of traits important for female choice while suppressing the immune system. Reciprocally, neuroendocrine-immune pathways can promote the development of altered behavioral states, such as sickness behavior. Understanding the energetic signals that mediate neuroendocrine-immune crosstalk is an active area of research. Although the field of psychoneuroimmunology (PNI) has begun to explore this crosstalk from a biomedical standpoint, the neuroendocrine-immune-behavior nexus has been relatively underappreciated in comparative species. The field of ecoimmunology, while traditionally emphasizing the study of non-model systems from an ecological evolutionary perspective, often under natural conditions, has focused less on the physiological mechanisms underlying behavioral responses. This review summarizes neuroendocrine-immune interactions using a comparative framework to understand the ecological and evolutionary forces that shape these complex physiological interactions.

Graphical abstract, Highlights • Ecoimmunology allows the study of parasite immunity in the context of genetic and environmental variation. • Studies in wild populations highlight the interactions between multiple variables. • Poor availability of immunological tools has hampered progress in non-model species. • Wild animal studies combine insights into host immunity and effects at population level. • We propose a virtuous cycle of testing hypotheses in both lab and wild systems., A wealth of research is dedicated to understanding how resistance against parasites is conferred and how parasite-driven pathology is regulated. This research is in part driven by the hope to better treatments for parasitic diseases of humans and livestock, and in part by immunologists who use parasitic infections as biomedical tools to evoke physiological immune responses. Much of the current mechanistic knowledge has been discovered in laboratory studies using model organisms, especially the laboratory mouse. However, wildlife are also hosts to a range of parasites. Through the study of host-parasite interactions in these non-laboratory systems we can gain a deeper understanding of parasite immunology in a more natural, complex environment. With a focus on helminth parasites, we here explore the insights gained into parasite-induced immune responses through (for immunologists) non-conventional experimental systems, and how current core findings from laboratory studies are reflected in these more natural conditions. The quality of the immune response is undoubtedly a central player in susceptibility versus resistance, as many laboratory studies have shown. Yet, in the wild, parasite infections tend to be chronic diseases. Whilst reading our review, we encourage the reader to consider the following questions which may (only) be answered by studying naturally occurring parasites in the wild: a) what type of immune responses are mounted against parasites in different hosts in the wild, and how do they vary within an individual over time, between individuals of the same species and between species? b) can we use wild or semi-wild study systems to understand the evolutionary drivers for tolerance versus resistance towards a parasite? c) what determines the ability of the host to cope with an infection and is there a link with the type of immune response mounted? d) can we modulate environmental factors to manipulate a wild animal’s immune response to parasitic infections, with translation potential for humans, wildlife, and livestock? and e) in context of this special issue, what lessons for Type 2 immunity can we glean from studying animals in their natural environments? Further, we aim to integrate some of the knowledge gained in semi-wild and wild settings with knowledge gained from traditional laboratory-based research, and to raise awareness for the opportunities (and challenges) that come with integrating a multitude of naturally-occurring variables into immunoparasitological research.

Almost all physiological processes within the organism, including immune parameters and hormones, follow a circadian rhythm. These daily fluctuations are often observed in free-living organisms; however, little is known regarding hormonal and immune daily variations in anurans, particularly under laboratory conditions. This study aimed to investigate the hormonal and immune daily variation in captive-bred Bullfrogs (Lithobates catesbeianus) under constant conditions (21 °C and 12:12 LD cycle). Our results showed a daily variation for plasma corticosterone (CORT), testosterone (T), and melatonin (MEL), as well as for blood leukocyte profile, phagocytic activity, and plasma bacterial killing ability (BKA). Hormonal profile and immune activity were higher at the dark when compared with the light phase; however, monocytes and lymphocytes followed the opposite pattern. Moreover, CORT was positively correlated with phagocytosis percentage of blood cells, BKA, and monocytes, while MEL and T showed a positive correlation with PP. Our results demonstrate the daily covariation of different immune variables and immunomodulatory hormones. These 24 h-day variations and covariation certainly have broad implications and need to be considered for better understanding anuran physiology both in the context of laboratory and field studies.

By determining susceptibility to disease, environment-driven variation in immune responses can affect the health, productivity and fitness of vertebrates. Yet how the different components of the total environment control this immune variation is remarkably poorly understood. Here, through combining field observation, experimentation and modelling, we are able to quantitatively partition the key environmental drivers of constitutive immune allocation in a model wild vertebrate (three-spined stickleback, Gasterosteus aculeatus). We demonstrate that, in natural populations, thermal conditions and diet alone are sufficient (and necessary) to explain a dominant (seasonal) axis of variation in immune allocation. This dominant axis contributes to both infection resistance and tolerance and, in turn, to the vital rates of infectious agents and the progression of the disease they cause. Our results illuminate the environmental regulation of vertebrate immunity (given the evolutionary conservation of the molecular pathways involved) and they identify mechanisms through which immunocompetence and host-parasite dynamics might be impacted by changing environments. In particular, we predict a dominant sensitivity of immunocompetence and immunocompetence-driven host-pathogen dynamics to host diet shifts.

Symbiotic relationships range from parasitic to mutualistic, yet all endosymbionts face similar challenges, including evasion of host immunity. Many symbiotic organisms have evolved similar mechanisms to face these challenges, including manipulation of the host's transforming growth factor-beta (TGFβ) pathway. Here we investigate the TGFβ pathway in scelaractinian corals which are dependent on symbioses with dinoflagellates from the family Symbiodiniaceae. Using the Caribbean coral, Orbicella faveolata, we explore the effects of enhancement and inhibition of the TGFβ pathway on host gene expression. Following transcriptomic analyses, we demonstrated limited effects of pathway manipulation in absence of immune stimulation. However, manipulation of the TGFβ pathway significantly affects the subsequent ability of host corals to mount an immune response. Enhancement of the TGFβ pathway eliminates transcriptomic signatures of host coral immune response, while inhibition of the pathway maintains the response. This is, to our knowledge, the first evidence of an immunomodulatory role for TGFβ in a scelaractinian coral. These findings suggest variation in TGFβ signaling may have implications in the face of increasing disease prevelance. Our results suggest that the TGFβ pathway can modulate tradeoffs between symbiosis and immunity. Further study of links between symbiosis, TGFβ, and immunity is needed to better understand the ecological implications of these findings.

Diseases spread by mosquitoes have killed more people than those spread by any other group of arthropod vectors and remain an important factor in determining global health and economic stability. The mosquito innate immune system can act to either modulate infection with human pathogens or fight off entomopathogens and increase the fitness and longevity of infected mosquitoes. While work remains towards understanding the larval immune system and the development of the mosquito immune system, it has recently become clearer that environmental factors heavily shape the developing mosquito immune system and continue to influence the adult immune system as well. The adult immune system has been well-studied and is known to involve multiple tissues and diverse molecular mechanisms. This review summarizes and synthesizes what is currently understood about the development of the mosquito immune system and includes comparisons of immune components unique to mosquitoes among the blood-feeding arthropods as well as important distinguishing factors between the anopheline and culicine mosquitoes. An explanation is included for how mosquito immunity factors into vector competence and vectorial capacity is presented along with a model for the interrelationships between nutrition, microbiome, pathogen interactions and behavior as they relate to mosquito development, immune status, adult female fitness and ultimately, vectorial capacity. Novel discoveries in the fields of mosquito ecoimmunology, neuroimmunology, and intracellular antiviral responses are highlighted.

Animals are attacked by pathogens, predators and competitors, sometimes simultaneously. For example, male crickets fight each other for access to females and such challenges may occur when one or both males are also defending themselves against a pathogen. We tested whether males altered their aggressive motivation when faced with both a competitor and a pathogen simultaneously. We found that immune-challenged male crickets (Gryllus texensis) were more likely to defeat male competitors when the reproductive payoff (i.e. a female) was nearby. However, when females were not present, males showed a decrease in their aggressive behaviour, and were less likely to win encounters with control males. This plasticity of aggressive motivation did not occur when males were chronically immune challenged. Chronically immune-challenged males were more likely to be defeated by control males regardless of the presence of a female. These results suggest that the costs associated with a chronic immune challenge may prevent terminal reproductive investment. We show that males can benefit from terminal reproductive investment because acutely immune-challenged males were still capable of mating and females did not appear to discriminate against them. Male crickets appear to engage in a context-dependent trade-off between the ability to defeat pathogens and the ability to defeat competitors. This trade-off is mediated, in part, by changes in male aggressive motivation (i.e. the critical threshold for the decision to flee).

The study of immunity has become an important area of investigation for researchers in a wide range of areas outside the traditional discipline of immunology. For the last several decades, psychoneuroimmunology (PNI) has strived to identify key interactions among the nervous, endocrine and immune systems and behavior. More recently, the field of ecological immunology (ecoimmunology) has been established within the perspectives of ecology and evolutionary biology, sharing with PNI an appreciation of the environmental influences on immune function. The primary goal of ecoimmunology is to understand immune function within a broadly integrative, organismal context, typically from an ultimate, evolutionary perspective. To accomplish this ecoimmunology, like PNI, has become a broadly integrative field of investigation, combining diverse approaches from evolution and ecology to endocrinology and neurobiology. The disciplines of PNI and ecoimmunology, with their unique yet complementary perspectives and methodologies, have much to offer one another. Researchers in both fields, however, remain largely unaware of each other's findings despite attempts at integration. The goal of this review is to share with psychoneuroimmunologists and other mechanistically-oriented researchers some of the core concepts and principles, as well as relevant recent findings, within ecoimmunology with the hope that this information will prove relevant to their own research programs. More broadly, our goal is to attempt to integrate both the proximate and ultimate perspectives offered by PNI and ecoimmunology respectively into a common theoretical framework for understanding neuro-endocrine-immune interactions and behavior in a larger ecological, evolutionary context.

Consistent, stable behavioural differences in how individuals respond to novel situations can lead to variation in exposure to pathogens. To minimize the costs associated with pathogen infection, animals have evolved behavioural and immunological strategies to avoid infection. However, because both behavioural and immunological defences are costly, host individuals should benefit from balancing investment in these defence strategies. It has been suggested that one such behavioural defence strategy is hesitancy to engage with novel objects and environments. In particular, exploratory individuals appear more likely to be exposed to novel pathogens than less exploratory individuals. Here, we tested the hypothesis that immune function is inversely related to behaviours with the potential to decrease exposure to pathogens (i.e. forgoing exploratory behaviours). We found an inverse association between aspects of innate immune function and exploratory behaviours. These observations suggest that individuals that engage in low-risk behaviours when experiencing a novel situation may invest less in some aspects of innate immune function than individuals that engage in high-risk behaviours. This individual variation in pathogen defence strategy is expected to affect the dynamics of pathogen spread through populations, and ultimately the course of epidemics.

Broadly distributed songbirds, particularly those that migrate, encounter a wide range of pathogens. Both pathogen exposure and energy available for immune responses are expected to be affected by environmental variation in climate, habitat quality, and social interactions as well as hormonal mechanisms. Comparisons of Aves in the field have begun to build the framework for understanding how such environmental variation interacts with disease environments as reflected in endocrine and immune responses. In this review, the roles of hormones and immune function across the various life history stages that make up the avian annual cycle are considered with an emphasis on free-living songbirds and the various hormones known to mediate the innate and acquired immune systems including melatonin, prolactin, growth hormone, and several neuroendocrine hormones. Finally, hormone-immune interactions are considered within the framework of disease ecology.

Avian pox virus (APV), a pathogen implicated as a major factor in avian declines and extinctions in Hawaii, was introduced to the Galápagos in the late 1890s. While APV is thought to have increased in prevalence in recent years, no study has carefully evaluated the threat this pathogen poses to the Galápagos avifauna. In this paper, we examine the course of the APV epidemic in seven species of Galápagos finch on Santa Cruz Island (Geospiza fuliginosa, G. fortis, G. magnirostris, G. scandens, Camarhynchus parvulus, Cactospiza pallida, and Certhidea olivacea). We describe temporal changes in the prevalence of the avian pox disease (AP) caused by APV and the proportion of individuals that have recovered from AP from 2000 to 2009. Then we examine species differences in susceptibility to AP and how this variation correlates with differences in innate immune function. We show that AP prevalence has increased dramatically from 2000 to 2009. However, this increase in prevalence varied by species; specifically, we found that prevalence increased rapidly in G. fuliginosa, C. parvulus, G. scandens, and C. olivacea, but not at all in G. fortis. Furthermore, innate immune function varies between years and species, and this variation correlates with increased prevalence and species variation in susceptibility to APV. To our knowledge, this is the first study to demonstrate significant interannual variation in innate immune function in wild birds, and to show that this immune variation correlates with susceptibility to an introduced disease. published

The phytohaemagglutinin (PHA) skin-swelling test is one of the most widely used methods for cell-mediated immunity measurement in immunoecology. Although several studies have investigated the condition-dependent traits associated with the magnitude of cutaneous inflammatory response to PHA, the results concerning signalling of the responsiveness through ornamental traits are still controversial. This is especially true for carotenoid-based feather ornamentation in birds. We therefore examined the linkage between several condition-dependent traits, including the red ornamental coloration of the plumage, and the magnitude of the PHA-induced immune response in scarlet rosefinch, Carpodacus erythrinus, males. Our results show two important aspects of the PHA-induced inflammation in this species. First, histological analysis showed that the swelling response was dependent on basophil activity. Second, the magnitude of the response (increase in patagium thickness) was associated with individual size, carotenoid-based ornamental coloration and a ptilochronological marker of feather growth at the time of moulting (mean growth bar width), thus mirroring the long-term quality of the individual. The positive linkage between the individual size or mean growth bar width and the PHA response suggests an association between the magnitude of the response and individual metabolic rate. However, as the magnitude of the response was also related negatively to ornament saturation and positively to ornament lightness, our results indicate stronger responsiveness in inferior males. Highly ornamented, healthier individuals recruited fewer basophils into the inflamed tissue causing less intense swelling. To our knowledge, this study is the first to show a negative association between carotenoid-based plumage coloration and the magnitude of the PHA-induced immune response.

Studies that blend a comparative approach to immunology with an appreciation for physiological ecology are defining an important new field in biology—ecological immunology. However, a panel of assays that permits a comparative approach to immunology is not yet available. In this paper, we describe several assays of innate immunity that do not require species-specific reagents and therefore ideal for use in comparative immunology studies. We optimized the assays for use in small birds, where sample volumes are limiting. The bactericidal assay measures the capacity of whole blood to kill microorganisms, and integrates many important components of constitutive immunity. The phagocytosis assay measures the phagocytic capacity of macrophages in whole blood. Bioassays for mannan binding protein and lysozyme can be used to measure inflammation-induced levels of these acute phase proteins in the plasma. Species differences in bactericidal and phagocytic activities against Staphylococcus aureus and Escherichia coli were observed in populations of captive and in free-living birds, demonstrating the assays’ utility for multi-species comparisons. However, clay-colored thrushes ( Turdus grayi ) that were stressed by prolonged capture and handling had diminished phagocytic and antibacterial activities, indicating the need to conduct these assays soon after capture. When birds were challenged with lipopolysaccharide (LPS), levels of mannan-binding protein, lysozyme, and haptoglobin were elevated and bactericidal and phagocytic activities of blood were altered, indicating that these measurements are sensitive to the current infection status of the animal. All assays could be done on as little as 10 μL of blood or plasma and should be useful in field studies of comparative immunity.

The function of the immune system of an animal is to provide defence against infection, in order to maximize fitness. Understanding this and, particularly, how limiting resources are traded off between costly immune responses and other physiological demands, is central to properly understanding life-history traits and their evolution. Here, we propose that functional (rather than immunological) measures of immune responses should be used when investigating this. We further suggest that optimal immune responses are context specific, rather than generic; that is, a maximum immune response is not necessarily optimal. The nature of an optimal immune response will depend on the specific circumstances and infection status of the animal. Identifying and understanding such optimality requires that the effects of different immune strategies on fitness be considered.

Evolutionary ecology has developed along two major conceptual avenues, starting from the observation that hosts vary in their immune defence against parasites The first avenue, rooted in life-history theory, assumes fitness costs of immune defence and tradeoffs in the face of limited resources, rather than specific host–parasite interactions. The second avenue focuses on specific responses, especially those generated by genotype–genotype interaction between and within host and parasite species. Specificity in the interactions between hosts and parasites play a crucial role in the field but analysis is difficult. Here, we classify concepts about host–parasite interactions into these two families and discuss their reconciliation with the help of a defence component model and two-dimensional classification scheme of the individual components. This helps to clarify some of the confusing terminology and might guide further research in the field.

The rate of reproduction, age at maturity and longevity vary widely among species. Most of this life-history variation falls on a slow-fast continuum, with low reproductive rate, slow development and long life span at one end and the opposite traits at the other end. The absence of alternative combinations of these variables implies constraint on the diversification of life histories, but the nature of this constraint remains elusive. Here, we argue that individual and adaptive responses to different environments are limited by physiological mechanisms. Although energy and materials allocations are important results of physiological tradeoffs, endocrine control mechanisms can produce incompatible physiological states that restrict life histories to a single dominant axis of variation. To approach the problem of life-history variation properly, studies should integrate behavior and physiology within the environmental and demographic contexts of selection.

View Large Image | Download PowerPoint SlideThe first self-declared ecoimmunology textbook has succeeded in a difficult task: thoughtful integration of multiple disciplines of biology, some of which tend to work at cross-purposes. The edited volume comprises 19 chapters aimed at researchers who study immune defence in an evolutionary context, and particularly in the context of life-history theory, as articulated by Ben Sheldon and Simon Verhulst in a now-classic paper in TREE over 15 years ago [1xEcological immunology: costly parasite defences and trade-offs in evolutionary ecology. Sheldon, B.C. and Verhulst, S. Trends Ecol. Evol. 1996; 11: 317–321Abstract | Full Text PDF | PubMed | Scopus (1274)See all References][1]. The core issue of ecoimmunology is to explain the adaptive significance of heterogeneity in immune defence, in light of life-history and resource trade-offs surrounding somatic maintenance (to which immunity is expected to contribute) versus growth and reproduction (from which immunity is expected to detract) [1xEcological immunology: costly parasite defences and trade-offs in evolutionary ecology. Sheldon, B.C. and Verhulst, S. Trends Ecol. Evol. 1996; 11: 317–321Abstract | Full Text PDF | PubMed | Scopus (1274)See all References, 2xOptimal immune responses: immunocompetence revisited. Viney, M.E. et al. Trends Ecol. Evol. 2005; 20: 665–669Abstract | Full Text | Full Text PDF | PubMed | Scopus (166)See all References]. An ecoimmunology textbook poses a difficult task because of the struggle to delve adequately into both the ‘hows’ and the ‘whys’ of that core issue; that is, how immune systems work, and why, evolutionarily, they work as they do. It is by striking a balance between hows and whys, above all, that Ecoimmunology succeeds.As I read, I was struck by many positives. For example, there is sound, realistic representation of infectious disease throughout: nearly all chapters address infection explicitly, which may be a sign that ecoimmunology is indeed becoming as connected to disease ecology as it should be [3xDisease ecology meets ecological immunology: understanding the links between organismal immunity and infection dynamics in natural populations. Hawley, D.M. and Altizer, S.M. Funct. Ecol. 2011; 25: 48–60CrossRef | Scopus (100)See all References][3]. Physiology and behavior are both well represented, and the authors have interestingly varied definitions of ecoimmunology. Furthermore, descriptions of mechanistic molecular and cellular details are nicely couched within ecological and evolutionary hypothesis tests, providing motivation for a TREE audience to embrace such details, or, at least, to persist despite the siege of acronyms that immunology inevitably entails. Reprinted original data figures provide welcome illustrations, and the schematic diagrams of immunological pathways provide insight without swamping readers in complexity. I think it is also safe to say that this is the first immunology textbook in the world to boast an adorable cover image.I did also find modest negatives. For example, invertebrates are under-represented and, in several places, authors present putative costs of immunity without any consideration of countervailing costs of parasitism. Throughout the book, conceptual figures (e.g., Venn and flow diagrams) are unimaginative and often text laden, so they convey the underlying ideas poorly. These are so pervasive that it seems they may have been forced upon the authors. This lapse is unfortunate and may mean that the potential audience will be more restricted than need be (especially problematic for newcomers to ecological and evolutionary immunology).However, my overriding impression was of well-grounded conceptual synthesis. The melding of immunological and evolutionary ideas serves to inspire, whereas the liberal acknowledgement of complexity and confusion in the literature, and the limits of assays and/or generalizations across taxa, serve to ground the book empirically. In particular, there is consensus among chapters that one-size-fits-all immune assays are not feasible. This is because different assays capture such different aspects of immunity that an assay drawn at random from the millions of possibilities is unlikely to be relevant to any given evolutionary hypothesis. Therefore, the book makes a strong case that the ‘hows’ and the ‘whys’ of immunity both matter. It should spark a great deal of research effort, including selection of empirical measurements that are more consistently relevant to the organisms or life-history traits under study.Thus, Ecoimmunology (like [4xBrave New World. Huxley, A. See all References][4]) does not present a dystopia with uncritical examination of where things stand. This truly is a brave new immunology. Indeed, whether wild [5xWild immunology. Pedersen, A.B. and Babayan, S.A. Mol. Ecol. 2011; 20: 872–880CrossRef | PubMed | Scopus (74)See all References][5], uncaged [6xBiomedical research. Immunology uncaged. Leslie, M. Science. 2010; 327: 1573CrossRef | PubMed | Scopus (9)See all References][6], or ecological [1xEcological immunology: costly parasite defences and trade-offs in evolutionary ecology. Sheldon, B.C. and Verhulst, S. Trends Ecol. Evol. 1996; 11: 317–321Abstract | Full Text PDF | PubMed | Scopus (1274)See all References, 7xAn introduction to ecological immunology. Martin, L.B. et al. Funct. Ecol. 2011; 25: 1–4CrossRef | Scopus (44)See all References, 8xIntroduction. Ecological immunology. Schulenburg, H. et al. Philos. Trans. R. Soc. Lond. B: Biol. Sci. 2009; 364: 3–14CrossRef | PubMed | Scopus (132)See all References], immunology is on the move, with recognition of the importance as well as the increasing feasibility of studying: (i) proper immunological mechanisms operating in nature; and/or (ii) genetic and ecologically induced variation in the laboratory. I am heartened by this book. I keenly await the future discoveries that are made possible by its synthetic and empirically grounded approach to the evolutionary ecology of immune defence.

The most commonly recognized behavioral patterns of animals and people at the onset of febrile infectious diseases are lethargy, depression, anorexia, and reduction in grooming. Findings from recent lines of research are reviewed to formulate the perspective that the behavior of sick animals and people is not a maladaptive response or the effect of debilitation, but rather an organized, evolved behavioral strategy to facilitate the role of fever in combating viral and bacterial infections. The sick individual is viewed as being at a life or death juncture and its behavior is an all-out effort to overcome the disease.