Changes In Immunocompetence Research Articles

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.

Cd28 Expression On Cd4+ T Cells Is Not Affected By Strenuous Exercise In Untrained Individuals

Optimal T cell activation requires a two-signal process. The first signal is engagement of the TCR-CD3 complex and the second, or costimulatory, signal is the classical binding of a T cell CD28 receptor with an APC-bound CD80 or CD86. A marker of senescent T cells is a lack of CD28 expression and it has been posited that CD28 expression may decrease following strenuous exercise. PURPOSE: To quantify exercise induced changes in CD28 expression on CD4+ cells obtained from human subjects. METHODS: Utilizing a cross over design, untrained subjects completed a control and exercise visit. The control visit consisted of 30 min of seated rest while the exercise session entailed 3 sets x 10 reps squat at 70% 1-RM, 3x10 leg press at 70% 1-RM, and 3x10 leg extensions at 70% 1-RM with 2 min rest between sets. Venous blood samples were obtained pre and post each visit. CD4+ T cell isolation from peripheral blood was conducted through negative selection using a Human CD4+ T cell enrichment kit. CD4+ T cells were plated at 1.5 x 106 cells/ml in 200 μl of ImmunoCult T-cell expansion media directly after isolation and costimulated through CD3+CD28 or no stimulation. Cells were incubated for 1 and 3 d at 37°C in a humidified incubator with 5% CO2 and then analyzed by flow cytometry. Data were analyzed using two-way RMANOVAs. RESULTS: There were no significant differences in CD28 expression between the exercise and control conditions in either the stimulated (p = .27) or non-stimulated (p = .62) samples. These data suggest that suppression of CD4+ cell activation following strenuous exercise is likely not a result of dysfunction in CD28, a major costimulatory receptor. CONCLUSIONS: Changes in T cell activation following strenuous exercise are likely derived from a plurality of sources, but without direct assessment of discrete elements of the activation cascade we will be unable to understand how exercise changes immune function. Future work should focus on elements upstream of T cell clonal expansion in order to identify mechanisms for exercise induced changes in immunocompetence. Supported by an award through the Dr. George F. Haddix President’s Faculty Research Fund at Creighton University.

Baseline and post-stress seasonal changes in immunocompetence and redox state maintenance in the fishing bat Myotis vivesi.

Little is known of how the stress response varies when animals confront seasonal life-history processes. Antioxidant defenses and damage caused by oxidative stress and their link with immunocompetence are powerful biomarkers to assess animal´s physiological stress response. The aim of this study was A) to determine redox state and variation in basal (pre-acute stress) immune function during summer, autumn and winter (spring was not assessed due to restrictions in collecting permit) in the fish-eating Myotis (Myotis vivesi; Chiroptera), and B) to determine the effect of acute stress on immunocompetence and redox state during each season. Acute stress was stimulated by restricting animal movement for 6 and 12 h. The magnitude of the cellular immune response was higher during winter whilst that of the humoral response was at its highest during summer. Humoral response increased after 6 h of movement restriction stress and returned to baseline levels after 12 h. Basal redox state was maintained throughout the year, with no significant changes in protein damage, and antioxidant activity was modulated mainly in relation to variation to environment cues, increasing during high temperatures and decreasing during windy nights. Antioxidant activity increased after the 6 h of stressful stimuli especially during summer and autumn, and to a lesser extent in early winter, but redox state did not vary. However, protein damage increased after 12 h of stress during summer. Prolonged stress when the bat is engaged in activities of high energy demand overcame its capacity to maintain homeostasis resulting in oxidative damage.

T cell activation and proliferation following acute exercise in human subjects is altered by storage conditions and mitogen selection

Recent work investigating exercise induced changes in immunocompetence suggests that some of the ambiguity in the literature is resultant from different cell isolation protocols and mitogen selection. To understand this effect, we compared post-exercise measures of T cell activation and proliferation using two different stimulation methods (costimulation through CD28 or stimulation with phytohaemagglutinin [PHA]). Further, we investigated whether exercise induced changes are maintained when T cell isolation from whole blood is delayed overnight in either a room temperature or chilled (4°C) environment. As expected, an increased proliferation response was observed post-exercise in T cells isolated from whole blood of previously trained individuals immediately after blood collection. Also, cells stimulated with PHA after resting overnight in whole blood were not adversely impacted by the storage conditions. In contrast, allowing cells to rest overnight in whole blood prior to stimulation through CD28, lessened the proliferation observed by cells following exercise rendering both the room temperature and chilled samples closer to the results seen in the control condition. Changes in early markers of activation (CD25), followed a similar pattern, with activation in PHA stimulated cells remaining fairly robust after overnight storage; whereas cell activation following stimulation through CD3+CD28 was disproportionately decreased by the influence of overnight storage. These findings indicate that decisions regarding cell stimulation methods need to be paired with the timeline for T cell isolation from whole blood. These considerations will be especially important for field based studies of immunocompetence where there is a delay in getting whole blood samples to a lab for processing as well as clinical applications where a failure to isolate T cells in a timely manner may result in loss of the response of interest.

An investigation of the immunotoxicity of oil sands processed water and leachates in trout leukocytes

Increased oil sands (OS) mining activity has raised concerns about impacts on aquatic organisms. This study sought to examine the effects of single representative compounds from OS (benzo(a)pyrene, naphthalene), a mixture of naphthenic acids (NAs), OS-processed water (OSPW) and OS leachate (OSL) extracts on rainbow trout leukocytes. Primary cultures of trout leukocytes were exposed to increasing concentrations of benzo(a)pyrene, naphthalene, NAs, OSPW and OSL for 48h at 18°C. Immunocompetence was followed by measuring changes in lymphocyte and macrophage viability and phagocytosis. Changes in the expression of 10 transcripts were also followed: interleukin 1, 2 and 6 (Il-1, Il-2 and Il-6), calreticulin (CRT), caspase 9 (Cas9), aryl hydrocarbon receptor (AhR), cyclooxygenase-2 (COX2), glutathione S-transferase (GST), catalase (CAT) and p53 tumor suppressor. The results revealed that exposure to OSPW extracts decreased the capacity of macrophages to engulf three beads or more, while the other compounds generally increased phagocytosis activity. Lymphocyte apoptosis was increased by all compounds and mixtures except naphthalene. Both OSPW and OSL induced apoptosis in macrophages. At the gene expression level, Cas9, CRT, Il-1 (inhibition) and Il-2 were specifically influenced by OSPW, while CAT, p53, COX2 and Il-1 (induction) transcripts were specifically expressed by OSL. Leukocyte exposure to OSPW produced characteristic changes in immunocompetence and genes involved in proinflammatory, apoptosis and protein damage (CRT) pathways which could not be explained by OSL, benzo(a)pyrene, naphthalene and NA mixture.

Evolution of Drosophila resistance against different pathogens and infection routes entails no detectable maintenance costs.

Pathogens exert a strong selective pressure on hosts, entailing host adaptation to infection. This adaptation often affects negatively other fitness-related traits. Such trade-offs may underlie the maintenance of genetic diversity for pathogen resistance. Trade-offs can be tested with experimental evolution of host populations adapting to parasites, using two approaches: (1) measuring changes in immunocompetence in relaxed-selection lines and (2) comparing life-history traits of evolved and control lines in pathogen-free environments. Here, we used both approaches to examine trade-offs in Drosophila melanogaster populations evolving for over 30 generations under infection with Drosophila C Virus or the bacterium Pseudomonas entomophila, the latter through different routes. We find that resistance is maintained after up to 30 generations of relaxed selection. Moreover, no differences in several classical life-history traits between control and evolved populations were found in pathogen-free environments, even under stresses such as desiccation, nutrient limitation, and high densities. Hence, we did not detect any maintenance costs associated with resistance to pathogens. We hypothesize that extremely high selection pressures commonly used lead to the disproportionate expression of costs relative to their actual occurrence in natural systems. Still, the maintenance of genetic variation for pathogen resistance calls for an explanation.

Assessment of immune response in periparturient dairy cows using ex vivo whole blood stimulation assay with lipopolysaccharides and carrageenan skin test

The transition period is known to be the most critical phase in the life of high yielding dairy cow. Changes in the immune functions have been observed during the transition period which may account for the onset of clinical and subclinical (e.g. inflammatory response) problems at calving or at the beginning of lactation however this relationship has not yet been adequately investigated. Thus, to establish the potential of the periparturient dairy cow's immune system to respond to stimuli, two challenges [an ex vivo whole blood stimulation assay (WBA) with lipopolysaccharides and a carrageenan skin test (CST)] were performed in addition to characterizing the metabolic and inflammatory profile. The WBA was performed using 0, 0.01 and 5μg LPS/mL on whole blood and CST was administered by subcutaneous injection of 0.7mL solution containing 4.2mg of carrageenan to the shoulder region of the cows. These tests were performed on 10 Holstein-Friesian cows at −45±2, −20±2, −3, 3, 7, 28±2 days from parturition (DFP). Cows were also monitored for health status, body condition score, milk yield. The results demonstrate a higher production of IL-1β and IL-6 from leukocytes after LPS stimulation around calving (from −3 to 3 DFP) compared to −45 DFP (P<0.05). Moreover, IL-6 (but not IL-1β) was able to reach close to the maximum response at the lower stimulus intensity (0.01μg LPS/mL), maintaining a higher response over a longer time in early lactation. The release of higher levels of IL-6 in the transition period, with low LPS dose, suggests its crucial role in the regulation of inflammatory response around calving. The response of cows to CST decreased a few days before calving (−3 DFP) compared with response at −45 and 28 DFP (P<0.05), and remained low in the first week of lactation. This result suggests the reduction of the functionality of some vascular factors, which decreases diapedesis. Overall, the WBA and CST tests confirm changes in immunocompetence around calving. These tests are able to better describe the changes of the innate immune response at a local and systemic level, mainly when combined with conventional metabolic and inflammatory indices.

Photoperiodic time measurement and seasonal immunological plasticity.

Seasonal variations in immunity are common in nature, and changes in day length are sufficient to trigger enhancement and suppression of immune function in many vertebrates. Drawing primarily on data from Siberian hamsters, this review describes formal and physiological aspects of the neuroendocrine regulation of seasonal changes in mammalian immunity. Photoperiod regulates immunity in a trait-specific manner, and seasonal changes in gonadal hormone secretion and thyroid hormone signaling all participate in seasonal immunomodulation. Photoperiod-driven changes in the hamster reproductive and immune systems are associated with changes in iodothyronine deiodinase-mediated thyroid hormone signaling, but photoperiod exerts opposite effects on select aspects of the epigenetic regulation of reproductive neuroendocrine and lymphoid tissues. Photoperiodic changes in immunocompetence may explain a proportion of the annual variance in disease incidence and severity in nature, and provide a useful framework to help understand brain-immune interactions.

Testosterone and Immune Function in Primates: A Brief Summary with Methodological Considerations

The endocrine system serves as a mediator by which the body integrates environmental cues to organize physiological alterations, including changes in immunocompetence. Hormones are central mechanisms that contribute to the onset and timing of key life history events, the allocation of time and energy between competing functions, and in general modulate phenotypic development and variation. Here we provide a very brief review of testosterone and immunity, which highlights the physiological costs that elevated testosterone levels can incur as a result of reproductive investments. We focus primarily on nonhuman primates where possible. Although there is substantial evidence that testosterone exerts some influences on immune responses, results from in vivo studies involving human and nonhuman primates have yielded equivocal results regarding such immunomodulatory actions. There may be several reasons for this, including variation in study design, immunological measures used, levels of other hormones present, host energy status, and even social conditions. We therefore review some of these potential methodological issues, concluding that increased care must be taken to analyze seasonal variability in energy budgets, to collect an adequate number of samples from known individuals, to account for status in the dominance hierarchy when applicable, and to use multiple measures of immunity. We must also seek to understand the collaborative effects of multiple hormones (particularly dehydroepiandrosterone and estradiol) with relation to their downstream immunological effects, assessing both individual and multiplicative actions in both males and females. Such efforts would benefit from the development of additional noninvasive immune measures for primates.

Phenoloxidase activity among developmental stages and pupal cell types of the ground beetle Carabus (Chaetocarabus) lefebvrei (Coleoptera, Carabidae)

In ecological immunology is of great importance the study of the immune defense plasticity as response to a variable environment. In holometabolous insects the fitness of each developmental stage depends on the capacity to mount a response (i.e. physiological, behavioral) under environmental pressure. The immune response is a highly dynamic trait closely related to the ecology of organism and the variation in the expression of an immune system component may affect another fitness relevant trait of organism (i.e. growth, reproduction).The present research quantified immune function (total and differential number of hemocytes, phagocytosis in vivo and activity of phenoloxidase) in the pupal stage of Carabus (Chaetocarabus) lefebvrei. Moreover, the cellular and humoral immune function was compared across the larval, pupal and adult stages to evaluate the changes in immunocompetence across the developmental stages. Four types of circulating hemocytes were characterized via transmission electron microscopy in the pupal stage: prohemocytes, plasmatocytes, granulocytes and oenocytoids. The artificial non-self-challenge treatments performed in vivo have shown that plasmatocytes and granulocytes are responsible for phagocytosis. The level of active phenoloxidase increases with the degree of pigmentation of the cuticle in each stage. In C. lefebvrei, there are different strategies in term of immune response to enhance the fitness of each life stage. The results have shown that the variation in speed and specificity of immune function across the developmental stages is correlated with differences in infection risk, life expectancy and biological function of the life cycle.

Changes in immunocompetence and other physiological measures during molt in Brown-headed Cowbirds (Molothrus ater)

ABSTRACT. We tested one of the foundational hypotheses of the field of ecological immunology: that it is difficult for animals to simultaneously carry out two or more especially demanding physiological processes at optimal levels because of energy needs or other factors that cause tradeoffs among competing components of life history. We investigated possible effects of molt (a costly life-history stage that all birds share) on three physiological parameters in 32 male and female Brown-headed Cowbirds (Molothrus ater). We measured hematocrit, corticosterone levels (CORT), and the bactericidal competence (BC) of blood plasma by drawing blood from the birds before, twice during, and twice after their molt from late July to early September 2009. In accordance with our predictions, BC dropped during molt for both males and females. Interestingly, BC recovered faster after molt ended in males, and female BC remained depressed for the rest of our sampling period. Hematocrit also dropped during the molt but retur...

Bacterial host resistance models in the evaluation of immunotoxicity

To assess potential immunomodulatory effects of a drug, pollutant, or natural product, an analysis of an exposed host’s ability to resist challenge with a viable bacteria is one of the best gauges. Many factors govern whether a host exposed to a test agent and then infected becomes ill or dies at rates greater than infected control counterparts. Beyond the status of the host’s immunocompetence, a bacterium’s route of entry into the host and its inherent virulence are important variables determining how (and rate at which) an infection resolves. A pre-determination of endpoint(s) to be defined is critical during planning of resistance assays. If a study is to determine overall changes in immunocompetence due to exposure (regardless of regimen or dosage of test agent), then assessing shifts in morbidity/mortality at a defined lethal dose [LD x ] value for the chosen route of infection would suffice. However, if a study is to define extent of immunomodulation in a particular body organ/cavity—or specific alterations in particular aspects of the humoral or cell-mediated immune responses—then careful selection of the pathogen, dose of the inoculum, means of infection of target site, and extent of the post-infection period to be examined, need to be made prior to host exposure to the test toxicant. This review will provide the Reader with background information about bacterial infections and how endpoint selection could be approached when designing resistance assays. An overview of protocols involved in the assays (e.g., bacterial preparation, host infection, post-infection endpoint analyses) and information about three bacteria that are among the most commonly employed in resistance assays is provided as well.

Breeding-related seasonal changes in immunocompetence, health state and condition of the cyprinid fish, Rutilus rutilus, L.

Seasonal changes in immunocompetence are predicted by the hypothesized trade-off between reproduction and self-maintenance, whereby immune function is a measure of self-maintenance and reproductive effort is seasonally dependent. We examined seasonal patterns in immunological, haematological and body condition parameters for male and female freshwater fish. In two different populations, the relative size of the spleen and the chemotaxic migration activity of head kidney granulocytes decreased immediately before and after spawning, respectively. Those decreases were accompanied by an increase in haematocrit values shortly before and after spawning in both populations and a decrease in the relative body weight in one population, possibly due to physiological stress caused by increased activity during the spawning period. Breeding-related changes in other measures studied (phagocytosis activity of head kidney granulocytes, blood IgM concentration, white cell count and red cell count) were absent or inconsistent. Some of the results are in line with the idea of a trade-off between reproduction and immune defence. The present data suggest that the differential responses of the immune system may have different temporal patterns, which should be taken into account in immunoecological studies. © 2003 The Linnean Society of London, Biological Journal of the Linnean Society , 2003, 78, 117−127.

Enhanced Recovery of NK Cell Activity in Mice under Restraint Stress by the Administration of a Biological Response Modifier Derived from the Mycelia of the Basidiomycete Tricholoma matsutake

Some types of stressor act on the immune system via the network comprising the endocrine-immune-nervous systems, and are reportedly responsible for the onset of diseases as well as giving impetus to their advance. It is important for the maintenance and promotion of health to cope with stress-induced changes in immunocompetence. Therefore, we studied the effects of administration of a novel biological response modifier (CM6271) derived from the mycelia of the basidiomycete Tricholoma matsutake on the NK cell activity in mice under restraint stress, in order to evaluate its potential to modulate immune responsiveness in stress-loaded individuals. (1) When C57BL/6 mice were restrained in 50-ml tubes for more than 6 h, splenic NK cell activity decreased significantly, but recovered gradually after the mice were released. The extent of the reduction of activity and the degree of recovery depended on the duration of the restraint. (2) The oral administration of CM6271 caused a significant acceleration of the recovery of the activity. This effect was dependent on the timing of administration and the dose given. (3) The administration of CM6271 had no clear effect on the blood levels of ACTH, corticosterone or lipid peroxide levels in the liver. These findings suggest that CM6271 promotes recovery from the decrease in NK cell activity induced by restraint stress.

Modulation of the fish immune system by hormones

Immune–neuroendocrine interactions in fish, as in mammals, have become a focus of considerable interest, with the modulation of immune responses by hormones receiving particular attention. Cortisol, growth hormone (GH), prolactin (PRL), reproductive hormones, melanin-concentrating hormone (MCH) and proopiomelanocortin (POMC)-derived peptides have all been shown to influence immune functions in a number of fish species. This review summarises the known effects of these hormones on the fish immune system, as well as the often complex interactions between different hormones. The possible implications for fish health, with respect to aquaculture and the changes in immunocompetence that take place during different stages in the fish life cycle are also discussed.

Micronutrient Supplementation does not Attenuate Seasonal Decline of Immune System Indexes in Well-nourished Elderly Women: A Placebo-Controlled Study

Immune system functioning declines as people age. In the elderly, increases in infectious diseases, malignancies, and autoimmune disorders maybe linked with changes in immunocompetence (1–3). Nutrition is generally accepted as an important determinant of immune functioning. Undernutrition is common and contributes to lowered immune responses in the elderly (4–6). In addition to the declines associated with aging, seasonal variations in immune activity have been identified (7–9). Age-related declines in immune function added to seasonal changes may put elderly persons at high risk of infections.

Immune function did not decline with aging in apparently healthy, well-nourished women

Nutrition plays a crucial role in immune function. Most studies on age-associated changes in immunocompetence in healthy adults did not examine the nutritional status of participants extensively. Inadequate nutritional status may confound the relationship of aging and immune response. The purpose of this study was to examine age-related changes in parameters of acquired and innate immunity in healthy and generally well-nourished older (62–88 years) versus younger (20–40 years) women. Subjects were screened for participation using the health criteria of the SENIEUR protocol as well as a number of nutrition criteria related to undernutrition, and protein, iron, vitamin B 12, and folate status. Young and old women did not differ in total T (CD3+), T-helper (CD4+), or T-cytotoxic (CD8+) cell number. However, older women tended to have lower T-cell proliferation response to concanavalin A ( P<0.10) and significantly reduced response to phytohemagglutinin ( P≤0.05). No age-related changes were noted in natural killer cell number or cytotoxicity. Phagocytosis and subsequent oxidative burst activity also did not differ between young and old women. Most immune parameters were not compromised with aging in this cohort of apparently healthy, well-nourished women. These findings highlight the importance of simultaneous examination of health and nutritional status in studies of immune function with aging.

Cocaine-induced release of corticosterone mediates differential effects on T-helper1 and T-helper2 cell responses.

Extensive research has been conducted to assess the effects of cocaine on immunocompetence, yet results have been difficult to interpret, with reports ranging from enhancement, to suppression, to no effect on immunity. Research conducted in our laboratory has assisted in clarifying some of these inconsistent results, and has revealed that cocaine exerts a biphasic effect on immune function via indirect mechanisms (Matulka 1994; Stanulis et al., 1997; Jeong et al., 1996; Holsapple et al., 1993). The antibodyforming cell (AFC) response is a sensitive measure of changes in immunocompetence, and it has been used to determine that at high doses (40–60 mg/kg), cocaine causes suppression through the release of reactive intermediates produced through P450 metabolism (Holsapple 1995). More interesting, however, is the observation that at lower doses (20–30 mg/kg) administered acutely, cocaine potentiates the AFC response, an effect which is mediated through the production of corticosterone via the hypothalamic-pitui tary-adrenal (HPA) axis. Additional research in our laboratory has revealed that the T-helper cell is the target for corticosterone’s effect (Stanulis et al., 1997).KeywordsCell CloneProliferative ResponseCorticosterone AdministrationHelper Cell ResponseAcute Cocaine AdministrationThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Molecular mechanisms of toxicant-induced immunosuppression: role of second messengers.

Changes in immunocompetence following chemical exposure have been established for a wide variety of unrelated agents. For the vast majority of immunotoxic compounds thus far identified, disruption of normal immune function is clearly mediated through direct interactions between the agent, or its metabolite, and immunocompetent cells. Regardless of whether this interaction occurs at the level of the cell membrane or at intracellular sites, basic regulatory processes mediated by second messengers are often altered. These alterations can ultimately result in immunologic dysfunction, which is most often manifested as immunosuppression. The specific disruptions in intracellular signaling produced by a number of immunotoxic compounds have now been identified, leading to a basic understanding of their molecular mechanism of action. Equally important, through the application of these agents as biological probes, new insights have been gained pertaining to which intracellular processes control which cellular functions within various populations of immunocompetent cells.

2,3,7,8-Tetrachlorodibenzo-p-Dioxin-Induced Changes in Immunocompetence: Possible Mechanisms

2,3,7,8-Tetrachlorodibenzo-p-Dioxin-Induced Changes in Immunocompetence: Possible Mechanisms