Aspects Of Immune Function Research Articles

Immunology-related perturbations induced by copper and chitosan in carp (Cyprinus carpio L.).

Copper is used in treatment mixtures to control fungal diseases in vineyards. Its concentrations are relatively high in some aquatic ecosystems, and the main problem observed in this study was the antioxidant stress induced by this heavy metal. Copper toxicologic effects in aquatic organisms have prompted the demand for alternative use of low-toxicity molecules in culture treatments. Chitosan is a polymer with antifungal property similar to copper and may be an interesting biopesticide. Thus, it is necessary to investigate the potential toxicity of chitosan for aquatic animal health, either alone or in conjunction with copper. In this study, carp were exposed to two sublethal chitosan concentrations (75 and 150 mg/L) or to two sublethal copper concentrations (0.1 and 0.25 mg/L) or to a mixture of chitosan plus copper (75 mg/L and 0.1 mg/L, respectively). The results of the present study show that exposure to copper at environmentally realistic levels or to chitosan at sublethal concentrations may significantly stimulate various aspects of immune functions in carp such as nonspecific cellular immunity, represented by total immunoglobulin level, ceruloplasmin activity, and oxidative activity of phagocytes. This acute-phase inflammatory response induced separately by the two treatments was not observed, especially on phagocyte oxidative activity, when carp were exposed to the copper-chitosan mixture. This fact could be explained by a possible chelation of copper by chitosan decreasing the biodisponibility of the two products for immune cells. Thus, the immunotoxicologic impact of copper and chitosan on fish immune response would be less pronounced with the combined treatments than with separate treatments in an aquatic environment.

Immune function and exercise

This review will examine the effects of exercise and training on immune func-tion and will discuss the methodological problems that limit the interpretation of many exercise immunology studies. Acute bouts of exercise cause a tempo-rary depression of various aspects of immune function, such as neutrophil oxidative burst, lymphocyte proliferation, monocyte MHC class II expression, and natural killer cell cytotoxic activity, that will usually last for approximately three to 24 hours after exercise, depending on the intensity and duration of the exercise bout. Post-exercise immune function depression is most pronounced when the exercise is continuous, prolonged (<1.5 hours), of moderate to high intensity (55-75% VO2max), and performed without food intake. Periods of intensified training that result in overreaching have been shown to chronically depress immune function—i.e., immune cell functions measured at rest are still depressed 24 hours after the last exercise bout. Although elite athletes are not clinically immune deficient, it is possible that the combined effects of small changes in several immune parameters may compromise resistance to common minor illnesses such as upper respiratory tract infection. Protracted immune depression linked with prolonged training may determine susceptibility to infection, particularly at times of major competitions.

Towards an understanding of the role of NOD2/CARD15 in the pathogenesis of Crohn's disease

With the recent discovery of NOD2 as the first susceptibility gene linked with Crohn's disease, research is now focused on attempting to explain the biological role of NOD2 and how mutations can contribute to the development of this inflammatory disease. Biochemical studies have revealed that NOD2 is in fact a protein involved in the innate immune detection of bacterial products. More specifically, NOD2 recognizes a fragment of peptidoglycan, called muramyl dipeptide, that is found in the cell walls of both Gram-negative and Gram-positive bacteria. This recognition event triggers a pro-inflammatory signalling cascade regulated by the transcription factor NF-κB. The complex cellular responses emanating from the interaction of NOD2 and its ligand are thought to touch on many aspects of immune function, including bacterial killing, cytokine release, stimulation and maturation of antigen-presenting cells, and the regulation of the adaptive immune response. Defining these NOD2-regulated responses, and how mutations in the gene encoding this protein disrupt these responses, will be key to understanding the pathogenesis of Crohn's disease.

Problems of breast cancer diagnosis during pregnancy and lactation

This review focuses on the effects of psychosocial interventions on psychological and biological functioning of breast cancer patients. Once in their lifetime, one out of eleven women receive a diagnosis of breast cancer. A diagnosis of breast cancer is a severe stressful life event with profound consequences on all aspects of human life. Whether a woman will regain emotional balance and accept the idea of living with a potentially life threatening disease depends on her psychological resiliency. Provision of psychosocial interventions can improve these women's coping abilities and reduce emotional distress and feelings of isolation, and improve psychosexual functioning. Additionally, there exists some evidence that psychotherapy may prolong survival. Prolongation of survival may be related, in part, to an increase in certain aspects of immune function (e.g., natural killer cell activity). This is plausible because the function of the immune system seems to be related to mammary tumor growth. Therefore, future research should examine the degree to which the effects on mammary tumor growth relate to immune system changes.

The role of gamma/delta T cells in immunity to infection and regulation of inflammation.

The role of gamma/delta T cells in immunity to bacterial infection and control of inflammation is discussed. Special emphasis is placed on the use of murine models in which various aspects of immune function can be monitored in the absence of gamma/delta T cells. Issues discussed include the response to and control of cytokine production by gamma/delta T cells. Especially relevant is the apparent paradox that gamma/delta T cells play both pro-inflammatory and antiinflammatory roles in response to infection.

Ectoparasite susceptibility in lizards from populations sympatric and allopatric with ticks

:Theory suggests that host-parasite interaction should lead to local adaptation of parasites to their hosts and vice versa. The degree of local adaptation depends on, for example, migration, relative generation time of host and parasite, and the number of host species. Furthermore, in any coevolutionary process, local adaptation of one species is dependent on the evolution of sympatric and allopatric populations of the other species, and the degree of gene flow. The tick Ixodes ricinus is a generalist tick feeding on hosts of a variety of taxa. We contrasted populations of common lizards (Lacerta vivipara) differing in their evolutionary history of exposure to ticks. Juvenile lizards were raised in a common garden experiment. We monitored growth rate, physiological performance, and aspects of immune function in tick-exposed and control offspring. There were no differences in response to tick infestation between host populations, with both sympatric and allopatric hosts showing impaired growth and endurance under parasite exposure. Ticks were marginally more engorged on allopatric hosts (P = 0.06); hence, our results do not support the hypothesis of local adaptation of parasites.

Inhibitory effects of low molecular weight heparin on mediator release by mast cells: preferential inhibition of cytokine production and mast cell-dependent cutaneous inflammation.

There has been substantial evidence that suggests that heparin may modulate various aspects of immune function and inflammation in addition to its well known anticoagulant activity. In this regard heparin was found to suppress cell-mediated immune responses or asthmatic reactions to allergen challenge. In the present study we analyse the effects of low molecular weight heparin (LMWH) on mast cell degranulation and cytokine production in vitro and on the elicitation of IgE-mediated mast cell-dependent late cutaneous allergic inflammation in vivo. We have established that LMWH preferentially inhibited tumour necrosis factor-alpha (TNF-alpha) and IL-4 production without having any significant effect on mast cell degranulation. These effects have been observed in mast cells derived from three different origins that were activated by either immunological or non-immunological stimuli. We have shown that there is inhibition of TNF-alpha production (and not neutralization of activity), as elimination of the drug after a short preincubation and addition of LMWH to rTNF-alpha had no effect on TNF-alpha-mediated cytotoxic activity. These results were also confirmed by ELISA. In vivo, s.c. injection of the LMWH inhibited the leucocyte infiltration associated with the late cutaneous response which followed passive cutaneous anaphylaxis (PCA) reaction, without affecting mast cell numbers or degranulation. These data suggest that LMWH may have an inhibitory role in mast cell-mediated allergic inflammation, and thus might be considered as a possible therapeutic modality.

Cyclooxygenase 2 (COX-2) as a target for therapy and noninvasive imaging

Prostaglandins modulate a wide range of biologic functions, including wound healing, temperature regulation, reproduction, and many aspects of immune function. Exaggerated production of prostaglandins contributes to a large number pathophysiologies. The critical enzyme in prostaglandin biosynthesis is prostaglandin synthase, also known as cyclooxygenase (COX). The nonsteroidal anti-inflammatory drugs (NSAIDs), one of the largest classes of pharmaceutical agents, exert most of their biologic effects by inhibiting cyclooxygenase production of prostaglandins. The discovery of a second, inducible form of cyclooxygenase, now known as COX-2, responsible for the production of prostaglandins in most pathological states, revived a relatively moribund research area in biochemistry, physiology, and pharmacology, and led to the search for and discovery of a new class of pharmacologic agents. The coxibs have greater efficacy and substantially ameliorated side effects when compared to the classic NSAIDs. Because of the pervasive role of COX-2 in a wide range of human pathologies, the coxibs have been the most successful entry into the pharmaceutical market in history, responsible for $6–10 billion in sales annually. The ability to noninvasively monitor COX-2 expression with molecular imaging probes will provide a corresponding advance in diagnosing COX-2-based disease, monitoring progression of such diseases, and evaluating alternative therapies.

Effect of water polo practice on cytokines, growth mediators, and leukocytes in girls.

The effects of exercise on growth and development are mediated through a complex interaction between the endocrine, immune, and nervous systems. Very little is known about how these systems respond to exercise in children or adolescents. Moreover, there are few studies that have examined growth factors, inflammatory cytokines, and leukocyte responses to "real-life" or field exercise solely in girls. Thus, the goal of the present study was to determine the acute exercise-induced alterations in the growth hormone --> insulin-like growth factor-I axis, inflammatory cytokines, and certain aspects of immune function in a group of adolescent girls after a typical water polo practice. Ten, healthy, high-school female subjects, 14-16 yr old, performed a single, typical, 1.5-h water polo practice session. Blood was sampled before and after the session. The exercise resulted in an increase in HR (from 82 +/- 2 to 161 +/- 5 beats.min(-1) at 30 min, P < 1.4.10(-6) ), as well as in circulating lactate levels (375 +/- 66%, P < 0.0005). Significant increases where noted in circulating IL-6 (396 +/- 162%, P < 0.005) and IL-1ra (71 +/- 20%, P < 0.015). A substantial increase in the level of IGFBP-1 (1344 +/- 344%, P < 0.001) was also observed. Interestingly, TNF-alpha levels decreased after the exercise (-10.4 +/- 3.8%, P < 0.04) as did insulin (55 +/- 12%, P < 0.005). The exercise led to significant increases in granulocytes, monocytes, and lymphocytes. The exercise significantly influenced adhesion molecules (such as CD62L and CD54), which has not been previously studied in adolescent girls. These data demonstrate that an intense "real-life" exercise bout in adolescent females leads to profound increases in inflammatory cytokines and reductions in anabolic mediators with substantial alterations in white blood cell subpopulations and adhesion molecules. The role of these frequent, almost daily immune and cytokine changes on growth and development have yet to be determined.

Problems and solutions to the development of vaccines in the elderly.

Scientists involved in vaccine research and development face the challenge of protecting the ever-increasing elderly population from a broad spectrum of infectious diseases. The optimal vaccine-induced immune response to confer protection is undefined for many pathogens, and the field of vaccine research is undergoing a gradual shift from the original focus on humoral immunity to a focus that incorporates cellular and innate immune components. The age-related changes in various aspects of immune function, including an increase in a population of T cells that shows signs of replicative senescence, underscore the need to enhance research aimed at designing vaccines to meet the unique requirements of the elderly population.

Early life environment: does it have implications for predisposition to disease?

Early life environmental factors have been associated with altered predisposition to a variety of pathologies. A considerable literature examines pre- and postnatal factors associated with increased risk of cardiovascular, metabolic (i.e. insulin resistance, hyperlipidemia) and psychiatric disease, and the importance of hormonal programming. The brain is exquisitely sensitive to environmental inputs during development and the stress responsiveness of the hypothalamic-pituitary-adrenal (HPA) axis has been shown to be both up- and down-regulated by early life exposure to limited nutrition, stress, altered maternal behaviors, synthetic steroids and inflammation. It has been suggested that peri-natal programming of HPA axis regulation might therefore contribute to metabolic and psychiatric disease etiology. In addition, glucocorticoids play modulatory roles regulating many aspects of immune function, notably controlling both acute and chronic inflammatory responses. Neuroendocrine-immune communication is bidirectional, and therefore it is expected that environmental factors altering HPA regulation have implications for stress effects on immune function and predisposition to inflammation. The impact of pre- and postnatal factors altering immune function, stress responsivity and predisposition to inflammatory disease are reviewed. It is also examined whether the early 'immune environment' might similarly influence predisposition to disease and alter neuroendocrine function. Evidence indicating a role for early life inflammation and infection as an important factor programming the neuroendocrine-immune axis and altering predisposition to disease is considered.

Manipulating neuroinflammatory reactions in the injured spinal cord: back to basics

Recruitment of inflammatory leukocytes to the injured spinal cord is a physiological response that is associated with the production of cytokines and proteinases that are involved in host defense and wound repair. Cells in the spinal cord are mainly post-mitotic and tissue regeneration is poor; thus, these inflammatory mediators can exacerbate the damage to spared tissue and thereby impair spontaneous functional recovery. Although several aspects of immune function might benefit the CNS, experimental studies indicate that acute neuroinflammation aggravates tissue injury. Until the timing and nature of the molecular signals that govern leukocyte recruitment and activation after spinal injury are defined, clinical therapies designed to boost immune cell function should be avoided.

An investigation into asymmetrical cortical regulation of salivary S-IgA in conscious man using transcranial magnetic stimulation

Transcranial magnetic stimulation (TMS) can activate discrete areas of the cerebral cortex through the intact skull of healthy conscious volunteers. A magnetic coil generates a brief and focused magnetic field that penetrates the skull to activate the specific area of cerebral cortex beneath. This non-invasive procedure is painless, well tolerated by participants and now widely used to explore brain function. We used TMS to investigate asymmetrical cortical regulatory influences on one aspect of immune function: secretion of the antibody immunoglobulin A (S-IgA) into saliva. The right and left temporo-parietal-occipital cortex of 16 healthy, conscious subjects was stimulated on two different occasions, at least 1 week apart. There was an immediate increase in S-IgA concentration following both right and left stimulation. Saliva volume was reduced immediately post-right but not left stimulation. When secretion (μg/min) of S-IgA was calculated (controlling for changing saliva volume) an increase was apparent following left but not right hemisphere stimulation. Furthermore, a significant difference between the relationship between S-IgA concentration and volume of saliva post-left and right stimulation was observed. We conclude that TMS can be used as a tool to investigate cortical regulation of autonomic and immune function in healthy, conscious human subjects and that secretion of saliva and S-IgA is differentially affected by stimulation of the left and right cerebral cortex.

Heritability of immune function in the caterpillar Spodoptera littoralis.

Phenoloxidase (PO) is believed to be a key mediator of immune function in insects and has been implicated both in non-self recognition and in resistance to a variety of parasites and pathogens, including baculoviruses and parasitoids. Using larvae of the Egyptian cotton leafworm, Spodoptera littoralis, we found that despite its apparent importance, haemolymph PO activity varied markedly between individuals, even amongst insects reared under apparently identical conditions. Sib-analysis methods were used to determine whether individuals varied genetically in their PO activity, and hence in one aspect of immune function. The heritability estimate of haemolymph PO activity was high (h(2) = 0.690 +/- 0.069), and PO activity in the haemolymph was strongly correlated with PO activity in both the cuticle and midgut; the sites of entry for most parasites and pathogens. Haemolymph PO activity was also strongly correlated with the degree to which a synthetic parasite (a small piece of nylon monofilament) was encapsulated and melanized (r = 0.622 +/- 0.142), suggesting that the encapsulation response is also heritable. The mechanism maintaining this genetic variation has yet to be elucidated.

Evaluation of phagocytosis and arachidonate metabolism by alveolar macrophages and recruited neutrophils from F344xBN rats of different ages

The incidence of infectious respiratory diseases increases with aging. Resident alveolar macrophages (AMs) and recruited leukocytes (PMNL) mediate cellular defense against bacterial infections in the lung, and phagocytosis and lipid mediator synthesis are important components of their antimicrobial capacity. The objective of this study was to determine if either phagocytic capacity or lipid mediator generation declines with normal aging, in either AMs or PMNL recruited to a site of inflammation. The F344xBN rat hybrid has a lower incidence of pathologies associated with aging, particularly up to 20 months; animals aged 6, 12 and 18 months were chosen to evaluate changes associated with normal aging. As previously reported for peripheral blood leukocytes, phagocytosis by recruited PMNL declined with aging: recruited PMNL from 18 months rats showed a significantly decreased capacity to phagocytose live Klebsiella pneumoniae bacteria, compared to PMNL from 6 months rats. Surprisingly, however, the phagocytic capacity of AMs increased with aging: the phagocytic index of AMs from 18 months rats was more than three times that of AMs from 6 months rats. The capacity of AMs and recruited PMNL to release arachidonic acid or synthesize leukotrienes or prostaglandins did not change with aging. This study demonstrates that, although phagocytosis by recruited PMNL declines with aging, other aspects of immune function do not decline, and may actually increase, with normal aging. These results suggest that impaired phagocytosis by recruited PMNL may be an important component of the increased susceptibility to infectious respiratory diseases during normal aging.

The impact of chronic estrogen deprivation on immunologic parameters in the ovariectomized rhesus monkey ( Macaca mulatta) model of menopause

A large clinical literature suggests that estradiol (E 2) plays a critical role in immune function. To further explore the relationship between E 2 and immune function, we examined a variety of immunological parameters in a rhesus monkey model of menopause and hormone replacement therapy. Rhesus monkeys (Age, 13.7±2.6 years) were ovariectomized and received either sham ( n=10) or estradiol ( n=10) replacement implants. Nine months post-ovariectomy, a variety of immunologic parameters were measured. E 2-deprivation reduced natural killer cell activity and increased serum soluble gp130 levels. There was a trend for an increased proportion of CD8 + ( P=0.12) and HLA-DR +CD3 + cells ( P=0.15) and decreased proportion of eosinophils ( P=0.11) in the E 2-deprived monkeys. There was no difference in leukocyte distribution, CD28, CD56, CD4, CD8/CD45, colony forming units-granulocyte/monocytes formation, peripheral blood mononuclear cell apoptotic rate, or serum TNF, TNF-R1, TNF-R2, IL-6, soluble IL-6R, and IL-1 between the groups. These data demonstrate that E 2-deprivation affects several aspects of immune function. These findings may have implications for menopause-associated changes of immune function that occur in women.

Ozone-Induced Modulation of Cell-Mediated Immune Responses in the Lungs

Most pulmonary immunotoxicology studies of ambient pollutants have been broadly designed to discern if overall humoral or cell-mediated immunity (CMI) was altered; few have assessed effects on particular aspects of immune function. We hypothesized that effects from ozone (O3) exposure on pulmonary CMI are linked in part to changes in local immune cell capacities to form and/or to interact with immunoregulatory cytokines. Rats exposed to 0.1 or 0.3 ppm O3 4 h/day 5 days/week, for 1 or 3 weeks were assessed for resistance to, and pulmonary clearance of, a subsequent Listeria monocytogenes challenge. In situ cytokine release and immune cell profiles were also analyzed at different stages of the antilisterial response. Although O3 exposure modulated CMI, effects were not consistently concentration- or duration-dependent. Exposure did not effect cumulative mortality from infection, but induced concentration-related effects upon morbidity onset and persistence. All 1-week exposed rats had listeric burdens trending higher than controls; 0.3 ppm rats displayed continual burden increases rather than any onset of resolution. Rats exposed for 3 weeks had no O3-related changes in clearance. No exposure-related effect on neutrophil or pulmonary macrophage (PAM) numbers or percentages was noted. Bacterial burden analyses with respect to cell type showed that Listeria:PAM ratios in 0.3 ppm rats ultimately became greatest compared to all other rats. In situ IL-1α and TNFα levels were consistently higher in O3-exposed rats. All rats displayed increasing in situ IFNγ levels as infection progressed, but no constant relationship was evident between IFNγ and initial IL-1α/TNFα levels in O3-exposed hosts. It seems that short-term (i.e., 1 week) repeated O3 exposures imparted more effects upon CMI than a more prolonged (i.e., 3 week) regimen, with effects manifesting at the level of the PAM and in the cytokine network responsible for immunoactivation.

Enteral glutamine feeding and some aspects of immune function in intensive care patients

Glutamine-enriched total parenteral nutrition (TPN) is beneficial in reducing both infective complications and mortality of critically ill patients. Similar results were observed in bone marrow transplant patients, as well as increased circulating numbers of lymphocytes, in particular T-cell subsets. An increase was observed in T-cell DNA synthesis in colorectal cancer patients receiving glutamine-enriched TPN. However, TPN is associated with complications such as intestinal atrophy, and enteral nutrition is now the preferred route. The present study assessed the effects of feeding glutamine enterally in 14 intensive care patients who were not immunosuppressed. Blood samples were analysed for plasma glutamine concentration (enzymatically), lymphocyte proliferation via 3H thymidine incorporation into DNA (counts per minute — CPM) with and without mitogenic stimulation (Concanavalin-A), neutrophil activity (using an oxidative burst technique) and cytokine production in culture medium (IL-2 and IL-8). Patients were randomly divided into two groups and fed 15-g bolus doses in water of either glutamine (n = 7; 60 ± 8 years) or placebo (n = 7; 60 ± 6 years) for 5 days. Nasogastric nutrition was discontinued daily at midday and a blood sample was taken; 1 hour later, a bolus dose of glutamine/placebo was administered via the tube; 2 hours later total nutrition was started again. Lymphocyte proliferation increased in the glutamine group (P < 0.04) compared with the placebo, as measured by CPM and the stimulation index. IL-2 production increased in culture medium from Day 0 to Day 5 for patients receiving glutamine (P < 0.02) compared with the placebo group. IL-8 production, neutrophil numbers or activity, and plasma glutamine did not change. Our results suggest that glutamine is able to induce an IL-2 mediated increase in the proliferative ability of T-cells, and we hypothesise that these changes may underlie previously observed clinical benefits from glutamine administration in critically ill patients.

Reproductive, immune, and physiological end points in tree swallows on reclaimed oil sands mine sites

AbstractWild nestling tree swallows (Tachycineta bicolor) inhabiting reclaimed wetlands receiving tailings or water from mine tailings ponds on oil sands mine sites were the subjects in a multiyear study to determine the ecological viability of these areas. Spanning two field seasons, immune function, reproductive performance (clutch size and mass, hatching success), nestling growth and survival, and diet of tree swallows were examined on six wetlands. One aspect of immune function, the T‐lymphocyte proliferative response, was assessed in vivo using a phytohemagglutinin skin test. Hepatic ethoxyresorufin‐O ‐deethylase (EROD) activityprovided a biomarker of exposure to oil sands contaminants in the tree swallow nestlings. Results show that there were no differences among reclaimed wetland sites for tree swallow reproductive success, nestling growth rate, and immune response that could be attributed to tailings or tailings pond water additions. Increased EROD activity confirmed the presence of xenobiotics in the diets of nestlings from two sites, while the main reference site was relatively free of EROD‐inducing compounds. Dietary analyses showed that 84% of the food items of the tree swallow nestlings were of aquatic origin, likely from the local wetlands, and thus would be expected to provide a good reflection of biological effects of any mining‐related contaminants accumulating through the food chain.

The level of protein and type of fat in the diet of pregnant rats both affect lymphocyte function in the offspring

Female rats were fed throughout pregnancy on diets which differed in the level of protein (90 or 180 g/kg) and the type of fat (100 g corn oil or 50 g corn oil + 50 g coconut oil or 10 g corn oil + 90 g coconut oil/kg) they contained. At birth they were transferred to standard laboratory chow. Thymocytes from neonates exhibited a strong proliferative response to the T-cell mitogen concanavalin A, whereas spleen lymphocytes did not. Lower protein intake during pregnancy impaired neonatal thymocyte proliferation by up to 80%. Thymic and spleen lymphocyte proliferation remained impaired at weaning for the offspring of dams fed the lower protein diet containing 100 or 50 g corn oil/kg. Lymphocytes from the offspring of dams fed the lower protein diet containing 90 g coconut oil/kg responded in a similar fashion to cells from the offspring of dams fed the diets containing 180 g protein/kg. Thus, the acquisition of lymphocyte responsiveness which was impaired at birth after prenatal exposure to a low protein diet could be overcome postnatally if the prenatal diet included a large amount of coconut oil and a small amount of corn oil. Spleen natural killer cell activity at weaning was lower following prenatal exposure to the low protein diet and was lower when coconut oil was included in the diet. Thus, some aspects of immune function are programmed in utero by factors related to the diet of the mother. The effects of the nutrients and other factors received during suckling and of the developmental changes in the immune system which occur postpartum appear unable to overcome the impact of the diet received in utero.