Variation In Immune Function Research Articles

Construction of a telomere-related gene signature to predict prognosis and immune landscape for glioma.

Glioma is one of the commonest malignant tumors of the brain. However, glioma present with a poor clinical prognosis. Therefore, specific detection markers and therapeutic targets need to be explored as a way to promote the survival rate of BC patients. Therefore, we need to search for quality immune checkpoints to support the efficacy of immunotherapy for glioma. We first recognized differentially expressed telomere-related genes (TRGs) and accordingly developed a risk model by univariate and multivariate Cox analysis. The accuracy of the model is then verified. We evaluated the variations in immune function and looked at the expression levels of immune checkpoint genes. Finally, to assess the anti-tumor medications often used in the clinical treatment of glioma, we computed the half inhibitory concentration of pharmaceuticals. We finally identified nine TRGs and built a risk model. Through the validation of the model, we found good agreement between the predicted and observed values. Then, we found 633 differentially expressed genes between various risk groups to identify the various molecular pathways between different groups. The enrichment of CD4+ T cells, CD8+ T cells, fibroblasts, endothelial cells, macrophages M0, M1, and M2, mast cells, myeloid dendritic cells, and neutrophils was favorably correlated with the risk score, but the enrichment of B cells and NK cells was negatively correlated with the risk score. The expression of several immune checkpoint-related genes differed significantly across the risk groups. Finally, in order to create individualized treatment plans for diverse individuals, we searched for numerous chemotherapeutic medications for patients in various groups. The findings of this research provide evidence that TRGs may predict a patient's prognosis for glioma, assist in identifying efficient targets for glioma immunotherapy, and provide a foundation for an efficient, customized approach to treating glioma patients.

Independent role of Alzheimer's disease genetics and C-reactive protein on cognitive ability in aging

Apolipoprotein E (APOE) ε4, the strongest genetic risk factor for late onset Alzheimer's disease (LOAD), has been associated with cognitive decline independent from AD pathology, but the role for other LOAD risk genes in normal cognitive aging is less studied. We examined the effect of APOE ε4 and several different polygenic risk scores (PRS) for LOAD on cognitive level and decline in aging, using longitudinal data from the UK Biobank. While PRS-LOAD including all variants (except APOE) predicted cognitive level, APOE ε4 and PRS-LOAD based on 17 non-APOE gene variants with strong association to AD (p < 5e-8) predicted age-related decline in verbal numeric reasoning. The effect on decline were partly driven by 4 variants involved in the immune system. Those variants also predicted serum levels of the inflammatory marker C-reactive protein (CRP), but CRP did not mediate the effect on decline. Those findings suggest genetic variations in immune functions play a role in aspects of cognitive aging that may be independent of LOAD pathology as well as systemic inflammation measured by CRP.

Human Variation in DNA Repair, Immune Function, and Cancer Risk.

DNA damage constantly threatens genome integrity, and DNA repair deficiency is associated with increased cancer risk. An intuitive and widely accepted explanation for this relationship is that unrepaired DNA damage leads to carcinogenesis due to the accumulation of mutations in somatic cells. But DNA repair also plays key roles in the function of immune cells, and immunodeficiency is an important risk factor for many cancers. Thus, it is possible that emerging links between inter-individual variation in DNA repair capacity and cancer risk are driven, at least in part, by variation in immune function, but this idea is underexplored. In this review we present an overview of the current understanding of the links between cancer risk and both inter-individual variation in DNA repair capacity and inter-individual variation in immune function. We discuss factors that play a role in both types of variability, including age, lifestyle, and environmental exposures. In conclusion, we propose a research paradigm that incorporates functional studies of both genome integrity and the immune system to predict cancer risk and lay the groundwork for personalized prevention.

Effect of Natural Seasonal Changes in Photoperiod and Temperature on Immune Function in Striped Hamsters.

What environmental factors contribute to seasonal variation in immune function in striped hamsters (Cricetulus barabensis) remains unclear. How immune responses would respond to natural seasonal changes in photoperiod and temperature was investigated in the present study. Twenty-nine male and 30 female hamsters were randomly assigned to the winter, spring, summer, and autumn groups. Spleen mass was the highest in male hamsters during autumn, while it did not differ among seasons in females. Regardless of sex, bacteria killing activity (BKA) was the lowest in the spring, whereas phytohaemagglutinin (PHA) responses at 12 h, 24 h, and 48 h were all highest in the winter among the four seasons. Females had the lowest titers of immunoglobin (Ig)G5, 10, and 15 in winter, while they did not show seasonal variation in males. Compared with male hamsters, females had higher levels of IgG10 and IgG15 in the spring and autumn, but had lower BKA in autumn. Blood glucose was the lowest in the spring in both sexes. Males had higher leptin level in winter than in summer and autumn, while leptin level was higher in winter and spring than in autumn in females. Corticosterone level was higher in winter and summer than in spring and autumn in males, while it was higher in winter than in the other three seasons in females. Males had higher levels of leptin in winter, and corticosterone in summer, than females. In summary, distinct parts of the immune system respond differently to natural seasonal variations in photoperiod and temperature.

Single-cell eQTL mapping identifies cell type-specific genetic control of autoimmune disease.

The human immune system displays substantial variation between individuals, leading to differences in susceptibility to autoimmune disease. We present single-cell RNA sequencing (scRNA-seq) data from 1,267,758 peripheral blood mononuclear cells from 982 healthy human subjects. For 14 cell types, we identified 26,597 independent cis-expression quantitative trait loci (eQTLs) and 990 trans-eQTLs, with most showing cell type-specific effects on gene expression. We subsequently show how eQTLs have dynamic allelic effects in B cells that are transitioning from naïve to memory states and demonstrate how commonly segregating alleles lead to interindividual variation in immune function. Finally, using a Mendelian randomization approach, we identify the causal route by which 305 risk loci contribute to autoimmune disease at the cellular level. This work brings together genetic epidemiology with scRNA-seq to uncover drivers of interindividual variation in the immune system.

A meta-analysis of impacts of immune response and infection on oxidative status in vertebrates.

Inferring from patterns observed in biomedical research, ecoimmunological theory predicts that oxidative stress is a ubiquitous physiological cost that contributes to generating variation in immune function between individuals or species. This prediction is, however, often challenged by empirical studies testing the relationship between immune response or infection and oxidative status markers. This points out the importance of combining ecological immunology and oxidative stress ecology to further our understanding of the proximate causes and fitness consequences of individual variation in health, and adaptability to natural and anthropogenic environmental changes. I reviewed evidence and performed phylogenetic meta-analyses of changes in oxidative status markers owing to either injection of an antigen or infection in captive and free-living vertebrates (141 studies, 1262 effect sizes, 97 species). The dataset was dominated by studies on fish, birds and mammals, which provided 95.8% of effect sizes. Both antigen injection and parasite exposure were associated with changes of oxidative status. There were significant effects of taxonomic class and experimental environment (captivity vs. wild). In contrast with my predictions, age category (young vs. adult), study design (correlational vs. experimental) and proxies of pace of life (clutch size, litter size, and body mass; for birds and mammals only) were negligible in this dataset. Several methodological aspects (type of immunostimulant, laboratory assay, tissue analysed) showed significant effects on both strength and direction of effect. My results suggest that alterations of oxidative status are a widespread consequence of immune function across vertebrates. However, this work also identified heterogeneity in strength and direction of effect sizes, which suggests that immune function does not necessarily result in oxidative stress. Finally, this work identifies methodological caveats that might be relevant for the interpretation and comparability of results and for the application in conservation programs.

Immune function differs among tropical environments but is not downregulated during reproduction in three\xa0year-round breeding equatorial lark populations

Seasonal variation in immune function can be attributed to life history trade-offs, and to variation in environmental conditions. However, because phenological stages and environmental conditions co-vary in temperate and arctic zones, their separate contributions have not been determined. We compared immune function and body mass of incubating (female only), chick-feeding (female and male), and non-breeding (female and male) red-capped larks Calandrella cinerea breeding year-round in three tropical equatorial (Kenya) environments with distinct climates. We measured four immune indices: haptoglobin, nitric oxide, agglutination, and lysis. To confirm that variation in immune function between breeding (i.e., incubating or chick-feeding) and non-breeding was not confounded by environmental conditions, we tested if rainfall, average minimum temperature (Tmin), and average maximum temperature (Tmax) differed during sampling times among the three breeding statuses per location. Tmin and Tmax differed between chick-feeding and non-breeding, suggesting that birds utilized environmental conditions differently in different locations for reproduction. Immune indices did not differ between incubating, chick-feeding and non-breeding birds in all three locations. There were two exceptions: nitric oxide was higher during incubation in cool and wet South Kinangop, and it was higher during chick-feeding in the cool and dry North Kinangop compared to non-breeding birds in these locations. For nitric oxide, agglutination, and lysis, we found among-location differences within breeding stage. In equatorial tropical birds, variation in immune function seems to be better explained by among-location climate-induced environmental conditions than by breeding status. Our findings raise questions about how within-location environmental variation relates to and affects immune function.

Effects of early-life conditions on innate immune function in adult zebra finches.

ABSTRACTEarly life conditions can affect individuals for life, with harsh developmental conditions resulting in lower fitness, but the underlying mechanisms are not well understood. We hypothesized that immune function may be part of the underlying mechanism, when harsh developmental conditions result in less effective immune function. We tested this hypothesis by comparing innate immune function between zebra finches (Taeniopygia guttata) in adulthood (n=230; age 108–749 days) that were reared in either small or large broods. We used this experimental background to follow up our earlier finding that finches reared in large broods have a shorter lifespan. To render a broad overview of innate immune function, we used an array of six measures: bacterial killing capacity, hemagglutination, hemolysis, haptoglobin, nitric oxide and ovotransferrin. We found no convincing evidence for effects of natal brood size on any of the six measures of innate immune function. This raised the question whether the origin of variation in immune function was genetic, and we therefore estimated heritabilities using animal models. However, we found heritability estimates to be low (range 0.04–0.11) for all measured immune variables, suggesting variation in innate immune function can largely be attributed to environmental effects independent of early-life conditions as modified by natal brood size.

Current and time-lagged effects of climate on innate immunity in two sympatric snake species.

Changing environments result in alterations at all levels of biological organization, from genetics to physiology to demography. The increasing frequency of droughts worldwide is associated with higher temperatures and reduced precipitation that can impact population persistence via effects on individual immune function and survival.We examined the effects of annual climate variation on immunity in two sympatric species of garter snakes from four populations in California over a seven‐year period that included the record‐breaking drought.We examined three indices of innate immunity: bactericidal competence (BC), natural antibodies (NABs), and complement‐mediated lysis (CL).Precipitation was the only climatic variable explaining variation in immune function: spring precipitation of the current year was positively correlated to Thamnophis sirtalis BC and NABs, whereas spring precipitation of the previous year was positively correlated to T. elegans BC and NABs. This suggests that T. elegans experiences a physiological time‐lag in response to reduced precipitation, which may reflect lack of capital for investment in immunity in the year following a dry year.In general, our findings demonstrate compelling evidence that climate can influence wild populations through effects on physiological processes, suggesting that physiological indices such as these may offer valuable opportunities for monitoring the effects of climate.

Ecoimmunology at spatial scales.

Becker, D. J., Albery, G. F., Kessler, M. K., Lunn, T. J., Falvo, C. A., Czirják, G. Á., Martin, L. B., & Plowright, R. K. (2020). Macroimmunology: The drivers and consequences of spatial patterns in wildlife immune defence. Journal of Animal Ecology, 89, 972-995. Ecoimmunology seeks to identify and explain natural variation in immune function. Most research so far has focused on differences among individuals within populations, which are often driven by trade-offs in resource allocation between energetically costly immunity and competing processes such as reproduction. In their review article, Becker et al. (2020) have proposed a framework to explicitly address habitat- and population-level differences in wildlife immune phenotypes. Termed macroimmunology, this concept integrates principles from ecoimmunology and macroecology. Becker et al. (2020) have highlighted three non-mutually exclusive habitat features that are likely to vary at spatial scales and influence immune function: (a) parasite pressure, (b) abiotic and biotic factors and (c) anthropogenic changes. However, a large and robust body of literature suitable for synthesis to detect macroimmunology patterns and effect sizes is not yet available. Through their systematic review and critical assessment, Becker et al. (2020) identified common problems in existing research that hinders spatial inferences, such as a need for spatial replication in study design and statistical analyses that account for spatial dependence. Overall, macroimmunology has the potential to identify and even predict spatial patterns in immune phenotypes that form the mechanistic underpinnings of important wildlife disease processes, and this review represents an important step to realizing these goals.

Inter-individual differences in immune profiles of outbred rats screened for an emotional reactivity phenotype

Inter-individual differences in emotional reactivity predict susceptibility versus resilience to mood pathology. Using experimentally-naïve outbred rats that vary in locomotor reactivity to the mild stress of an inescapable novel environment [i.e., top and bottom 1/3rd of the population identified as high responders (HR) and low responders (LR) respectively], we determined baseline variations in immune functions. Innate and adaptive immune responses vary basally in LRHR rats, namely a shift towards TH1 in LRs and TH2 in HRs was observed. These inter-individual variations in immune profiles in LRHRs could have significant implications in mood alterations and immune reactivity to microbes and cancer.

A fruit diet rather than invertebrate diet maintains a robust innate immunity in an omnivorous tropical songbird.

Diet alteration may lead to nutrient limitations even in the absence of food limitation, and this may affect physiological functions, including immunity. Nutrient limitations may also affect the maintenance of body mass and key life‐history events that may affect immune function. Yet, variation in immune function is largely attributed to energetic trade‐offs rather than specific nutrient constraints.To test the effect of diet on life‐history traits, we tested how diet composition affects innate immune function, body mass and moult separately and in combination with each other, and then used path analyses to generate hypotheses about the mechanistic connections between immunity and body mass under different diet compositions.We performed a balanced parallel and crossover design experiment with omnivorous common bulbuls Pycnonotus barbatus in out‐door aviaries in Nigeria. We fed 40 wild‐caught bulbuls ad libitum on fruits or invertebrates for 24 weeks, switching half of each group between treatments after 12 weeks. We assessed innate immune indices (haptoglobin, nitric oxide and ovotransferrin concentrations, and haemagglutination and haemolysis titres), body mass and primary moult, fortnightly. We simplified immune indices into three principal components (PCs), but we explored mechanistic connections between diet, body mass and each immune index separately.Fruit‐fed bulbuls had higher body mass, earlier moult and showed higher values for two of the three immune PCs compared to invertebrate‐fed bulbuls. These effects were reversed when we switched bulbuls between treatments after 12 weeks. Exploring the correlations between immune function, body mass and moult, showed that an increase in immune function was associated with a decrease in body mass and delayed moult in invertebrate‐fed bulbuls, while fruit‐fed bulbuls maintained body mass despite variation in immune function. Path analyses indicated that diet composition was most likely to affect body mass and immune indices directly and independently from each other. Only haptoglobin concentration was indirectly linked to diet composition via body mass.We demonstrated a causal effect of diet composition on innate immune function, body mass and moult: bulbuls were in a better condition when fed on fruits than invertebrates, confirming that innate immunity is nutrient specific. Our results are unique because they show a reversible effect of diet composition on wild adult birds whose immune systems are presumably fully developed and adapted to wild conditions—demonstrating a short‐term consequence of diet alteration on life‐history traits.

Not going with the flow: Locomotor activity does not constrain immunity in a wild fish.

Immunity is a central component of fitness in wild animals, but its determinants are poorly understood. In particular, the importance of locomotory activity as a constraint on immunity is unresolved. Using a piscine model (Gasterosteus aculeatus), we combined a 25‐month observational time series for a wild lotic habitat with an open flume experiment to determine the influence of locomotor activity (countercurrent swimming) on natural variation in immune function. To maximize the detectability of effects in our flume experiment, we set flow velocity and duration (10 cm/s for 48 hr) just below the point at which exhaustion would ensue. Following this treatment, we measured expression in a set of immune‐associated genes and infectious disease resistance through a standard challenge with an ecologically relevant monogenean infection (Gyrodactylus gasterostei). In the wild, there was a strong association of water flow with the expression of immune‐associated genes, but this association became modest and more complex when adjusted for thermal effects. Our flume experiment, although statistically well‐powered and based on a scenario near the limits of swimming performance in stickleback, detected no countercurrent swimming effect on immune‐associated gene expression or infection resistance. The field association between flow rate and immune expression could thus be due to an indirect effect, and we tentatively advance hypotheses to explain this. This study clarifies the drivers of immune investment in wild vertebrates; although locomotor activity, within the normal natural range, may not directly influence immunocompetence, it may still correlate with other variables that do.

Revisiting the tuberculosis and leprosy cross-immunity hypothesis: Expanding the dialogue between immunology and paleopathology

ObjectiveOur primary objective is to re-visit the tuberculosis and leprosy cross-immunity. hypothesis through the careful integration of immunology and paleopathology. MethodsUsing an integrated theoretical analysis that evaluates clinical literature on human innate immunological responses, paleomicrobiology, bioarchaeology, and paleopathology, we develop a multifactorial model. ResultsPast populations do not represent homogeneous immunological landscapes, and therefore it is likely that leprosy in Medieval Europe did not uniformly decline due to cross-immunity. ConclusionsWe recommend that bioarchaeological reconstructions of past disease experience take into consideration models that include variation in immune function based on past environments and social contexts. This provides a unique opportunity to conduct comprehensive analyses on complex immunological processes. SignificanceExtrapolating results from experimental immunology to larger populations elucidates complexities of disease cross-immunity and highlights the importance of synthesizing archaeological, social, paleopathological and biological data as a means of understanding disease in the past. LimitationsAll extrapolations from data produced from in vitro studies to past populations, using living donors, pose significant limitations where, among other factors, the full reconstruction of past environmental and social contexts can frequently be sparse or incomplete. Suggestions for future researchTo reduce the limitations of integrating experimental immunology with bioarchaeological reconstructions (i.e. how to use skeletal samples to reconstruct inflammatory phenotypes), we propose that osteoimmunology, or the study of the interplay between immune cells and bone cells, should be considered a vital discipline and perhaps the foundation for the expansion of paleoimmunology.

Avian Health across the Landscape: Nestling Immunity Covaries with Changing Landcover.

The landscape composition of an organism's home range or territory should influence aspects of its condition, including measures of immune function. Changes in immunocompetence arising from variation in landcover may provide important links between habitat changes and patterns of disease spread. To establish a baseline understanding for whether immune measures covary with changes in landcover, we examined associations between immunological parameters and landcover composition for adults and nestlings of five shrubland bird species. Specifically, we examined the bacteria-killing ability (BKA) of the blood plasma and profiles of the five avian leukocytes as our measures of immune function, and assessed the proportion of area around each bird's nest that was composed of the four major landcover types in the Midwestern USA: row crop agriculture, developed, forest, and grass/shrub. We performed landcover assessments at 100 and 1000 m radius buffers to identify whether associations between habitat and immune function differed at the two spatial scales. As part of this work, we examined age and species-related immunological variation, as well as associations among the immune parameters. There was little evidence linking variation in immune function to landcover composition for the adults at either spatial scale, but there were numerous associations for nestlings, and these were stronger at the 1000 than 100 m spatial scale. The proportion of grass/shrub around the nest had the largest impact on immune function, although the effect varied by immune parameter and species. BKA and basophils were inversely associated with grass/shrub for all species, whereas lymphocytes were positively associated with grass/shrub for all species. We also documented species-level differences among adults and nestlings for BKA and all leukocytes except monocytes. As expected, we found that nestlings had reduced levels of BKA, lymphocytes, monocytes, and elevated heterophils compared with adults (except for field sparrow-Spizella pusilla-nestlings, which had higher lymphocytes). Basophils generally did not differ by age class, and eosinophils exhibited species-specific patterns, in which they were higher for nestling American robins (Turdus migratorius) and gray catbirds (Dumetella carolinensis) compared with adults, but lower in the other nestlings. Heterophils and lymphocytes were inversely associated for all species and age classes, and basophil levels were positively associated with BKA across species and age classes. Together, these findings bolster our understanding of age and species-specific variation in immune function, and provide evidence that immune measures can covary with changes in landcover.

Immune cell characteristics and cytokine responses in adult HIV-negative tuberculous meningitis: an observational cohort study

Immunopathology contributes to high mortality in tuberculous meningitis (TBM) but little is known about the blood and cerebrospinal fluid (CSF) immune response. We prospectively characterised the immune response of 160 TBM suspects in an Indonesian cohort, including 67 HIV-negative probable or definite TBM cases. TBM patients presented with severe disease and 38% died in 6 months. Blood from TBM patients analysed by flow cytometry showed lower αβT and γδT cells, NK cells and MAIT cells compared to 26 pulmonary tuberculosis patients (2.4-4-fold, all p < 0.05) and 27 healthy controls (2.7-7.6-fold, p < 0.001), but higher neutrophils and classical monocytes (2.3-3.0-fold, p < 0.001). CSF leukocyte activation was higher than in blood (1.8-9-fold). CSF of TBM patients showed a predominance of αβT and NK cells, associated with better survival. Cytokine production after ex-vivo stimulation of whole blood showed a much broader range in TBM compared to both control groups (p < 0.001). Among TBM patients, high ex-vivo production of TNF-α, IL-6 and IL-10 correlated with fever, lymphocyte count and monocyte HLA-DR expression (all p < 0.05). TBM patients show a strong myeloid blood response, with a broad variation in immune function. This may influence the response to adjuvant treatment and should be considered in future trials of host-directed therapy.

Tools to understand seasonality in health: quantification of microbe loads and analyses of compositional ecoimmunological data reveal complex patterns in Mojave Desert Tortoise (Gopherus agassizii) populations

Using data from six wild Mojave Desert Tortoise (Gopherus agassizii (Cooper, 1861)) populations, we quantified seasonal differences in immune system measurements and microbial load in the respiratory tract, pertinent to this species’ susceptibility to upper respiratory tract disease. We quantified bacteria-killing activity of blood plasma and differential leukocyte counts to detect trends in temporal variation in immune function. We used centered log-ratio (clr) transformations of leukocyte counts and stress that such transformations are necessary for compositional data. We tested animals for the potential pathogen Pasteurella testudinis Snipes and Biberstein, 1982 with a newly created quantitative polymerase chain reaction (qPCR) assay, as well as for the known respiratory pathogens Mycoplasma agassizii Brown et al., 2001 and Mycoplasma testudineum Brown et al., 2004. We found very little disease and suggest that P. testudinis is a prevalent, commensal microbe in these Mojave Desert Tortoise populations, and its quantification may be a tool to study natural fluctuations in microbe levels in Mojave Desert Tortoise respiratory tracts. Our analyses showed that both the potential for inflammatory responses and microbe levels are highest in the spring for healthy Mojave Desert Tortoises, when lymphocyte levels are lowest. The genetic and statistical tools that we used are easily applicable to other wildlife systems and provide the necessary data to quantify species-wide trends in health and test hypotheses pertinent to host–microbe dynamics.

Research progress on the role of melatonin and its receptors in animal reproduction: A comprehensive review.

Melatonin and its receptors play a crucial role in the regulation of the animal reproductive process, primarily in follicular development. However, the role that melatonin performs in regulating hormones related with reproduction remains unclear. Melatonin and its receptors are present both in female and male animals' organs, such as ovaries, heart, brain and liver. Melatonin regulates ovarian actions and is a key mediator of reproductive actions. Melatonin has numerous effects on animal reproduction, such as protection of gametes and embryos, response to clock genes, immune-neuroendocrine, reconciliation of seasonal variations in immune function, and silence or blockage of genes. The growth ratio of reproductive illnesses in animals has raised a remarkable concern for the government, animal caretakers and farm managers. In order to resolve this challenging issue, it is very necessary to conduct state-of-the-art research on melatonin and its receptors because melatonin has considerable physiognomies. This review article presents a current contemporary research conducted by numerous researchers from the entire world on the role of melatonin and its receptors in animal reproduction, from the year 1985 to the year 2017. Furthermore, this review shows scientific research challenges related to melatonin receptors and their explanations based on the findings of 172 numerous research articles, and also represents significant proficiencies of melatonin in order to show enthusiastic study direction for animal reproduction researchers.

Seasonal variations in cellular and humoral immunity in male striped hamsters (Cricetulus barabensis).

ABSTRACTAnimals in the non-tropical zone usually demonstrate seasonal variations in immune function, which is important for their survival. In the present study, seasonal changes in immunity in striped hamsters (Cricetulus barabensis) were investigated to test the winter immunoenhancement hypothesis. Male hamsters were captured from the wild in the fall and winter of 2014 and in the spring and summer of 2015. Body mass, body fat mass and blood glucose levels of the hamsters were all highest in the summer, whereas relative fatness and thymus mass had no seasonal changes. Spleen mass was highest in the fall and white blood cells and phytohaemagglutinin (PHA) response indicative of cellular immunity were lowest in the summer among the four seasons, which supports the winter immunoenhancement hypothesis. IgG and IgM titers were lowest in the fall, which was against this hypothesis. Body fat mass had no correlations with cellular and humoral immunity, suggesting it was not the reason for seasonal changes in cellular and humoral immunity in males. Leptin titers were higher in spring and summer than in fall and winter. No correlation between leptin and cellular and humoral immunity suggested that leptin did not mediate their seasonal changes. Similarly, corticosterone levels were also higher in spring and summer than in fall and winter, which correlated negatively with cellular immunity but positively with IgG levels. This result implied that corticosterone has a suppressive effect on cellular immunity and an enhancing effect on humoral immunity. In summary, distinct components of immune systems exhibited different seasonal patterns. This article has an associated First Person interview with the first author of the paper.

A Return to Wisdom: Using Sickness Behaviors to Integrate Ecological and Translational Research.

Sickness is typically characterized by fever, anorexia, cachexia, and reductions in social, pleasurable, and sexual behaviors. These responses can be displayed at varying intensities both within and among individuals, and the adaptive nature of sickness responses can be demonstrated by the context-dependent nature of their expression. The study of sickness has become an important area of investigation for researchers in a wide range of areas, including psychoneuroimmunology (PNI) and ecoimmunology (EI). The general goal of PNI is to identify key interactions among the nervous, endocrine and immune systems and behavior, and how disruptions in these processes might contribute to disease states. EI, in turn, has been established more recently within the perspectives of ecology and evolutionary biology, and is aimed more at understanding natural variation in immune function and sickness responses within a broadly integrative, organismal, and evolutionary context. The goal of this review is to examine the literature on sickness from both basic and biomedical perspectives within PNI and EI and to demonstrate how the integrative study of sickness behavior can serve as an integrating agent to connect ecological and translational approaches to the study of disease. By focusing on a set of specific exemplars, including the energetics of sickness, social context, and environmental influences on sickness, we hope to accomplish the larger goal of developing a common synthetic framework to understand sickness from multiple levels of analysis and varying perspectives across the fields of PNI and EI. By applying this integrative approach to sickness, we will be able to develop a more comprehensive view of sickness as a suite of adaptive responses rather than the simply deleterious consequences of illness.