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Nutritional modulation of immune function in broilers.

Collaborative research efforts across disciplines typically result in more insight toward the hypothesis being tested due to the omnibus nature of the projects. For example, nutritional experiments evaluating a nutrient response will benefit greatly by incorporating biochemical, physiological, and immunological endpoints for measurement. Clearly, commercial poultry producers do not have the luxury of focusing on specific disciplines when field problems occur. Hence, in practice interplay exists among nutrition, genetics, management, and diseases. Dietary composition impacts immune function of the chicken. As research in the area of nutritional immunology has increased, it is becoming apparent that nutrient needs for immunity do not coincide with those for growth or skeletal tissue accretion. This review is not a comprehensive assessment of nutrient needs for immunity in the chicken. Rather, this review is concerned with nutritional modulation of immunity in broilers that offers insight for nutritionists and researchers to implement nutritional regimens to reduce the severity of disease and to test or validate nutritional regimens that heighten immunity. Nutritional modulation of the hen diet and in ovo nutrient modulation to improve chick immunity and disease resistance are discussed.

Amino Acids↗

Varicella-zoster virus productively infects mature dendritic cells and alters their immune function.

Mature dendritic cells (DCs) are potent antigen-presenting cells essential for initiating successful antiviral immune responses and would therefore serve as an ideal target for viruses seeking to evade or delay the immune response by disrupting their function. We have previously reported that VZV productively infects immature DCs (A. Abendroth, G. Morrow, A. L. Cunningham, and B. Slobedman, J. Virol. 75:6183-6192, 2001), and in the present study we assessed the ability of VZV to infect mature DCs. Mature DCs were generated from immature monocyte-derived DCs by lipopolysaccharide treatment before being exposed to VZV-infected fibroblasts. On day 4 postexposure, flow cytometry analysis revealed that 15 to 45% of mature DCs were VZV antigen positive, and immunofluorescent staining together with infectious-center assays demonstrated that these cells were fully permissive for the complete VZV replicative cycle. VZV infection of mature DCs resulted in a selective downregulation of cell surface expression of the functionally important immune molecules major histocompatibility complex (MHC) class I, CD80, CD83, and CD86 but did not alter MHC class II expression. Immunofluorescent staining showed that the downregulation of cell surface CD83 was concomitant with a retention of CD83 in cytoplasmic vesicles. Importantly, VZV infection of mature DCs significantly reduced their ability to stimulate the proliferation of allogeneic T lymphocytes. These data demonstrate that mature DCs are permissive for VZV and that infection of these cells reduces their ability to function properly. Thus, VZV has evolved yet another immune evasion strategy that would likely impair immunosurveillance and enhance the chances for lifelong persistence in the human population.

Antigen Presentation↗

Stress management effects on psychological, endocrinological, and immune functioning in men with HIV infection: empirical support for a psychoneuroimmunological model.

We present a psychoneuroimmunologic (PNI) model for Human Immunodeficiency Virus (HIV) infection, describe a 10-week group-based cognitive behavioral stress management (CBSM) intervention and summarize research demonstrating the effects of this intervention on mood, neuroendocrine (Hypothalamic Pituitary Adrenal [HPA], Hypothalamic Pituitary Gonadal [HPG] and Sympathetic Nervous System [SNS] hormones) and immune system status (lymphocyte subsets, anti-viral immune function) in HIV-infected persons. This work demonstrates that changes in relaxation skills, cognitive coping strategies and social support may mediate the mood effects of CBSM, and that these mood changes may mediate adrenal hormone regulation indicated by reductions in 24-h urinary cortisol (with reduced depressed mood) and norepinephrine (with reduced anxiety) and increases in serum DHEA-S and testosterone levels (with reduced depressed mood). Results also suggest that CBSM-related changes in production of these hormones may explain, in part, the effects of this intervention on short-term changes in IgG antibody titers to herpesviruses (with increased DHEA-S-to-cortisol ratio), and longer-term changes in lymphocyte subpopulations such as CD8 suppressor/cytotoxic cells (with reductions in urinary noradrenaline output) and transitional naïve CD4 cells (with reductions in urinary cortisol output). Thus a multi-modal CBSM intervention is associated with alterations in mood, neuroendocrine functioning and immunologic status that may have health implications for HIV infection.

Cognitive Behavioral Therapy↗

Gut microenvironment and immune function.

Overreaction of the acute phase response is responsible for the two major complications to surgery, sepsis and thrombosis, but also most likely for the leading sequela to surgery, adhesion formation. The gastrointestinal tract, especially the colon, is a major player in the acute phase response and responsible for important immune functions with important interactions between the commensal flora, mucosal cells and the mucosa/gut associated lymphoid tissues. These responses can effectively be modulated by enteral nutrition, provided it is properly composed and administered. There is increasing evidence that the important clinical effects sometimes observed in enteral nutrition are more related to immunostimulatory effects than to reduction in microbial translocation. It is suggested that in order to be effective enteral nutrition should be instituted if possible before the operation, but always at least immediately after. Furthermore, much supports that the formula given should contain what has been called colonic food, e.g. plant fibres, and have a low content of saturated fat. Use of antibiotics with deleterious effects on the commensal flora should also be limited as much as possible. Lack of compliance with these requests seems to explain the lack of consistency in clinical experience of enteral nutrition, when tried in connection with trauma and clinical surgery.

Acute-Phase Reaction↗

Immune function in patients with beta thalassaemia receiving the orally active iron-chelating agent deferiprone.

Short-term deferiprone may reduce body iron in some patients with thalassaemia major. Concerns regarding potential immunosuppressive effects of deferiprone have been raised from results of animal studies and case reports in humans. We studied immune function in 57 thalassaemia patients: 36 treated with deferiprone (L1; CP020) and 21 treated with desferrioxamine (DFO). Circulating B lymphocytes were increased in all patient groups. No differences were detected between treatment groups in percentages of circulating lymphocytes, concentrations of IgG, IgM or IgA, specific antibody titres, complement levels, or in vitro lymphocyte proliferation. No clinically important infections were observed in any patient. These data suggest that no clinical or laboratory changes consistent with immuno-suppression or immunodeficiency are observed during deferiprone therapy.

Adolescent↗

Immunomodulation by isoprinosine: effects on in vitro immune functions of lymphocytes from humans with autoimmune diseases.

Isoprinosine (IPS) is a new anti-viral agent which appears to have immunomodulatory activities which include its ability to enhance the in vitro blastogenic responses of normal lymphocytes to mitogens. The present study compares the effects of IPS on the in vitro immune functions of peripheral blood mononuclear cells (PBMC) from systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) patients with its effects on PBMC from normal controls. Each mitogen (Con A, PHA or PWM) was used at its optimal concentration with a range of IPS concentrations (0-25 micrograms/ml). PHA-induced blastogenesis by PBMC from all three groups was enhanced by IPS at or above 5 micrograms/ml. The Con A-induced responses of SLE lymphocytes were significantly enhanced over controls by IPS (P less than 0.02 at 5 micrograms/ml) while those of RA lymphocytes were not. IPS had little effect on PWM-induced blastogenesis by RA lymphocytes but did enhance the blastogenic responses of SLE lymphocytes (P less than 0.01 at 5 micrograms/ml). In contrast, the characteristically high immunoglobulin synthesis by SLE lymphocytes was decreased by IPS. The mechanism responsible for these effects is not known but IL-2 production by patient lymphocytes in vitro which was low for both RA (P less than 0.01) and SLE (P less than 0.02) increased significantly (P less than 0.05) when SLE lymphocytes were cultured with IPS. These data identify IPS as an agent for the study of aberrant immune regulation in autoimmune diseases and suggest that it may have potential therapeutic value in SLE.

Adult↗

Biomarkers as early predictors of long-term health status and human immune function.

A central issue that must be addressed by phytonutrient research is how to assess the effects of phytonutrients on long-term health. Proper assessment of these effects requires the measurement of biomarkers of long-term health in people consuming any particular phytonutrient. This is a brief review of what is known about biomarkers of cancer risk, immune function, and aging. Relatively few biomarkers of long-term health have been even partially validated in experimental animals or people.

Aging↗

Immune function in patients with Shwachman-Diamond syndrome.

Shwachman-Diamond syndrome (SDS) is an inherited multisystem disorder characterized by exocrine pancreatic dysfunction and varying degrees of cytopenia. In addition, various immunological abnormalities have been noted. To clarify the issue of immunological competence or incompetence in SDS, we prospectively studied immune function in 11 patients with SDS. Seven suffered from recurrent bacterial infections and six from recurrent viral infections. Varying degrees of impairment were readily identified. All patients had neutropenia; total lymphocyte counts, however, were normal in all except one patient. Nine patients had B-cell defects comprising one or more of the following abnormalities: low IgG or IgG subclasses, low percentage of circulating B lymphocytes, decreased in vitro B-lymphocyte proliferation and a lack of specific antibody production. Seven out of nine patients studied had at least one T-cell abnormality comprising a low percentage of total circulating T lymphocytes or CD3+/CD4+ cell subpopulations or decreased in vitro T-lymphocyte proliferation. Five out of six patients studied had decreased percentages of circulating natural killer cells. Moreover, neutrophil chemotaxis was significantly low in all the patients studied. These data point to a major immunodeficiency component in SDS that places patients at heightened risk of infections, even if neutrophil numbers are protective. This finding broadens the definition of the syndrome substantially: it suggests that the SDS marrow defect occurs at the level of an early haematological-lymphocytic stem cell or that a combined marrow and thymic stromal defect accounts for the aberrant function of haematopoietic and lymphopoietic lineages.

Adolescent↗

[An experimental study on the effects of lingzhi spore on the immune function and 60Co radioresistance in mice].

Lingzhi spore (2 g.kg-1.d-1, 10 times) was orally administered to mice, and studies were carried out on the carbon clearance, delayed-type skin hypersensitivity (DTH), antibody hemagglutinin value and spleen weight. The results showed that Lingzhi spore could increase the immune function, inhibit the reduction of white blood cells and raise the survival rate of mice after they were radiated by 870 rad 60Co.

Animals↗

Stress and immune function: a bibliographic review.

Environmental stressors are involved in the etiology of important livestock diseases, including transmissible gastroenteritis in young pigs, Newcastle's and Marek's disease in chickens and shipping fever in cattle. Unfortunately, very little research has been conducted to learn how stress alters host resistance, although it is generally assumed that the immune system of the host is affected. This paper identifies eight stressors that typically occur in modern livestock production units: heat, cold, crowding, mixing, weaning, limit-feeding, noise and restraint. All of these stressors have been shown to alter the immune system of animals. These changes in immune function may ultimately explain the physiological basis of disease-environment interactions. A thorough understanding of stress-induced changes in host resistance will also provide the scientific basis for effective prophylactic therapy. More controlled experiments are needed to learn how stress alters the susceptibility of animals to infectious and noninfectious diseases.

Animal Feed↗

Effects of recombinant interferon-alpha on immune function in cancer patients.

Patients with a variety of malignancies were treated in phase I clinical trials of recombinant leukocyte A interferon (IFL-rA) schedules consisting of either twice-daily doses for 28 days (48 patients) or three times weekly for 28 days (86 patients). Extensive monitoring of several immune functions was done on these patients, with rigorously standardized assays and determination of inherent variability of function for each individual. The assays performed were natural killer (NK) cell cytotoxicity, monocyte cytostatic activity, lymphoproliferative responses to concanavalin A (con A) and mixed leukocyte culture, and an analysis of changes in leukocyte populations as determined using a panel of monoclonal antibodies and flow cytometry. No appreciable increase in NK activity was observed on any of the treatment regimens, and an unexpected observation was the depression of activity in a substantial proportion (30%) of patients. In contrast, monocyte function, as measured in an assay of growth inhibition of tumor target cells, was found to be elevated in 70% of the patients. Lymphoproliferative responses were depressed in most patients in response to both con A and the mixed leukocyte culture. Cell surface marker studies revealed an increase in the percentage of OKT10 positive cells in the majority of patients studied and a transient increase in cells reacting with the antibody MO2. The data have been analyzed in terms of their relationship to dose and schedule of administration, and the depression of NK activity was shown to be greatest at the highest doses and more frequent schedule of administration.

Clinical Trials as Topic↗

[Suppressive effects of safflower yellow on immune functions].

Safflower yellow (SY) extracted from Carthamus tinctorius L contained chalconoid compounds, 75% of which was safflomin A. SY ip 50-450 mg.kg-1.d-1 x 6-8 d in mice decreased serum lysozyme concentration and phagocytosing functions of both peritoneal macrophages and peripheral leukocytes; diminished the production of plaque forming cells, specific rosette forming cells, and antibody; inhibited delayed type hypersensitivity reaction and the activation of T suppressor cells elicited by supraoptimal immunization. Experiments in vitro showed inhibitory effects on [3H]TdR incorporation during human peripheral T- and B-lymphocyte proliferation by SY 0.03-3.0, 0.1-2.0 mg.ml-1 respectively, murine mixed lymphocyte culture response and the production of interleukin-2 by SY 0.1-2.5 mg.ml-1. In conclusion, SY produced declines in both nonspecific and specific immune functions.

Animals↗

Impaired immune function in patients with xeroderma pigmentosum.

The development of contact allergy in sun-exposed skin is markedly impaired in patients with xeroderma pigmentosum as compared to the responses in healthy control subjects. The degree of this immunological impairment is directly related to the severity of the cutaneous disease. These findings raise the possibility that sunlight-induced alterations of immune function may be involved in the marked susceptibility of these patients to the development of nonmelanoma skin cancer.

Adolescent↗

Regulation of immediate early gene expression by exercise: short cuts for the adaptation of immune function.

Onset of physical activity induces a wide variety of rapid biophysical and biochemical responses that act on cells and lead to a wide range of phenotypic adaptations. Here we elucidate the role of immediate early gene (IEG) expression as a first line of transcriptional response that mediates protein neosynthesis and leads to adaptation of immune function. New posttranscriptional mechanisms have been described that speed up transcriptional responses. These include RNA-RNA interactions such as those exploited by miRNAs and stimulus-dependent cytoplasmic polyadenylation. We describe these shortcuts that modulate expression and discuss the challenges of accurately measuring them using various transcriptomic screening and quantification approaches. Although there is high complexity of the upstream as well as the downstream pathways that lead to IEG expression, IEG expression itself may only show a limited number of response patterns. Focusing transcriptomic approaches in exercise immunology at the IEG-level may facilitate the discovery of exercise-specific transcriptional signatures.

Adaptation, Physiological↗

Immune functions of cord blood cells before and after transplantation.

There have been numerous reports of decreased acute and chronic graft-versus-host disease in patients receiving HLA-matched or HLA-disparate umbilical cord transplants. It has been proposed that this may be due to the unique properties of the neonatal immune system, which permit the development of tolerance to alloantigens. This review discusses experimental evidence contrasting the immune functions of cells derived from cord blood and those from peripheral blood.

Antigens, CD↗

The effect of longterm treatment with auranofin and gold sodium thiomalate on immune function in the dog.

Although gold compounds are recognized as effective immunomodulatory agents in the treatment of rheumatoid arthritis (RA), their mechanism of action is controversial. We examined the effect of longterm treatment with 0.6-3.6 mg/kg auranofin (AF) per os q24h, or intramuscular injections of 0.5-2.0 mg/kg gold sodium thiomalate (GSTM) q3d, on 13 variables of immune function in normal dogs. None of the changes in these variables previously attributed to treatment with AF or GSTM could be demonstrated after 6-7 years' dosing. As gold compounds are effective in treating spontaneous RA in dogs, these proposed actions may not be responsible for the remittive effects of chrysotherapy in this disease.

Animals↗

The major histocompatibility complex-encoded HFE in iron homeostasis and immune function.

HFE is a non-classical major histocompatibility complex class I molecule that complexes with a beta2-microglobulin. A functional link between HFE and iron metabolism has been established by the discovery of a physical association between HFE and the transferrin receptor. By inhibiting transferrin receptor internalization, HFE functions as a negative modulator of transferrin receptor function. In addition, HFE appears to be an iron sensor that directly or indirectly communicates the body's iron status to T cells, which then use cytokines as feedback modulators to achieve iron homeostasis. A working model for the feedback regulatory mechanism between iron metabolism and immune function is proposed.

Biological Transport, Active↗