The clinical significance of micronutrients in relation to immune functions.
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Animals↗
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Cytological basis of immune functions of the spleen. Immunocytochemical characterization of lymphoid and non-lymphoid cells involved in the 'in situ' immune response.
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Animals↗
Contributions of mesangial cells to glomerular immune functions.
Mesangial cells play an important role in the maintenance of the structure and function of the glomerulus. In addition mesangial cells are capable of macromolecular uptake, and generation of autocoids and cytokines. Our studies have explored the mechanism of IgG uptake by cultured rat mesangial cells. Mesangial cells were found to express Fc receptors for IgG as demonstrated by specific binding studies, indirect immunofluorescence microscopy, immunoblotting and Northern blot analysis. The number of Fc receptors for IgG on mesangial cells was upregulated by interferon gamma, cyclic AMP and monocyte-macrophage specific colony stimulating factor--CSF-1. In addition uptake of IgG complexes was acutely increased by angiotensin II and inhibited by cAMP. These latter effects are independent of receptor number, but are mediated by changes in the cytoskeleton. These observations may be of significance for hemodynamically independent effects of vasoactive agents on mesangial function. Finally we examined the potential of mesangial cells for generation of CSF-1. Cultured mesangial cells produced radioimmunoassayable CSF-1 and expressed mRNA for CSF-1. Interferon gamma stimulated, whereas cAMP and agents increasing cAMP, such as forskolin and PGE2, inhibited CSF-1 production. This was due to decreased transcription resulting in lower levels of mRNA for CSF-1. The interactions of CSF-1, other cytokines, prostaglandins and cAMP may be important in regulating immune-like functions of mesangial cells, and especially their response to immunecomplexes.
Angiotensin II↗
Immune functions are maintained in healthy men with low zinc intake.
Although immunity is impaired during severe zinc deficiency, there is limited information about the effects of mild zinc depletion on immune response in humans. We evaluated the effects of a zinc-restricted diet (4.6 mg/d) on several indices of immunity in 8 healthy men. The subjects consumed zinc supplements with 9.1 mg/d during the 5-wk baseline (BL) and 5-wk repletion (RP) periods, and placebos during the 10-wk zinc-restriction (ZR) period. Leukocyte numbers and functions were studied at the end of each metabolic period. After ZR, there were reductions in the proliferation of peripheral blood mononuclear cells (PBMNC) stimulated with phytohemagglutinin (PHA, 1.2, 2.5, 5.0, 10.0 [corrected] and 20.0 mg/L; P < 0.01) and in the in vitro secretion of interleukin-2 receptor (IL-2R) (PHA, 2.5 mg/L; P = 0.058). These variables remained reduced (P < 0.05) even after 5 wk of zinc repletion. The amount of zinc consumed did not alter the numbers of circulating neutrophils, monocytes and lymphocytes, the in vitro PBMNC secretion of interferon-gamma and tumor necrosis factor-alpha or neutrophil superoxide production. The results suggest that changes in lymphocyte proliferation and IL-2R expression may be early markers of mild zinc deficiency.
Adult↗
Testosterone-mediated immune functions and male life histories.
Recent advances in human life history theory have provided new insights into the potential selection pressures that were instrumental in the evolution of human and non-human primate males. However, gaps remain in our understanding of how primate males regulate and allocate energetic resources between survivorship and reproductive effort. Defense against parasitic infection is an important force shaping life history evolution. Proper performance of immunological responses against infection is influenced by many physiological systems, including metabolic, reproductive, and stress hormones. Because androgens influence and modulate immune, reproductive, and somatic metabolic functions, assessing changes in testosterone and immune factors during infection may yield insight into male physiological ecology. In this review, we examine male life history trade-offs between immune and reproductive endocrine functions as well as provide a comprehensive review of testosterone-immunocompetence relationships. Emphasis is placed on testosterone because it is a primary hormone shown to be crucial to energy-allocation processes in vertebrates. Non-primate species have been used more extensively in this research than humans or non-human primates, and therefore this extensive literature is organized and reviewed in order to better understand potential parallel relationships in primates, especially humans. Furthermore, we attempt to reconcile the many inconsistent results obtained from field studies on immune-endocrine interactions as well as detail various methodologies that may be used to forward this research in evolutionary anthropology.
Animals↗
The effects of ozone on immune function.
A review of the literature reveals that ozone (O3) exposure can either suppress or enhance immune responsiveness. These disparate effects elicited by O3 exposure depend, in large part, on the experimental design used, the immune parameters examined as well as the animal species studied. Despite the apparent contradictions, a general pattern of response to O3 exposure can be recognized. Most studies indicate that continuous O3 exposure leads to an early (days 0-3) impairment of immune responsiveness followed, with continued exposures, by a form of adaptation to O3 that results in a re-establishment of the immune response. The effects of O3 exposure on the response to antigenic stimulation also depend on the time at which O3 exposure occurred. Whereas O3 exposure prior to immunization is without effect on the response to antigen, O3 exposure subsequent to immunization suppresses the response to antigen. Although most studies have focused on immune responses in the lung, numerous investigators have provided functional and anatomical evidence to support the hypothesis that O3 exposure can have profound effects on systemic immunity.
Animals↗
Examining the relationship between impaired host resistance and altered immune function in mice treated with TCDD.
Exposure to TCDD suppresses the immune response to numerous antigens, including bacterial and viral pathogens. Although we administer a non-lethal infection with influenza A virus, we often observe significant mortality in TCDD-treated animals. With the goal of identifying which TCDD-induced defects impair host resistance, we conducted a dose response study to examine whether alteration of particular immunological endpoints could be correlated with mortality. C57Bl/6 mice were treated with vehicle control, or 1, 2.5, 5, 7.5 or 10 microg/kg TCDD 1 day prior to intranasal (i.n.) infection with influenza virus. Survival was monitored for 9 days, when remaining mice were sacrificed and multiple endpoints evaluated. Lymphocyte migration to the lung and the production of virus-specific IgG2a, IgG1, and IgG2b antibodies were significantly diminished, even at the lower doses. IgA was enhanced in all groups treated with TCDD. In contrast, T cell expansion in the lymph node, and the production of IFNgamma and IL-12 were relatively resistant to suppression. Treatment with TCDD also enhanced pulmonary neutrophilia in infected mice. These results suggest that decreased antibody production and hyperinflammation may contribute to the death of TCDD-treated mice, and underscore the importance of evaluating numerous endpoints before concluding that a chemical is or is not immunotoxic.
Animals↗
Immune function during space flight.
It is very likely that the human immune system will be altered in astronauts exposed to the conditions of long-term space flight: isolation, containment, microgravity, radiation, microbial contamination, sleep disruption, and insufficient nutrition. In human and animal subjects flown in space, there is evidence of immune compromise, reactivation of latent virus infection, and possible development of a premalignant or malignant condition. Moreover, in ground-based space flight model investigations, there is evidence of immune compromise and reactivation of latent virus infection. All of these observations in space flight itself or in ground-based models of space flight have a strong resonance in a wealth of human pathologic conditions involving the immune system where reactivated virus infections and cancer appear as natural consequences. The clinical conditions of Epstein-Barr-driven lymphomas in transplant patients and Kaposi's sarcoma in patients with autoimmune deficiency virus come easily to mind in trying to identify these conditions. With these thoughts in mind, it is highly appropriate, indeed imperative, that careful investigations of human immunity, infection, and cancer be made by space flight researchers.
Aerospace Medicine↗
Development of mucosal immune function in man: potential for GI disease states.
The human mucosal immune system is structurally mature and has all the necessary cellular components to generate an immune response at birth. However, in the absence of dietary antigens and bacterial flora, there are no secondary follicles in the Peyer's patches and virtually no immunoglobulin A plasma cells in the lamina propria. Reactive follicle centers develop after birth but it takes 2 years for mucosal IgA plasma cell density to reach adult levels. T cells are present in the epithelium and lamina propria at birth, albeit at a lower frequency than later in life and there are major differences in phenotype between T cells in fetal intestine and postnatal intestine. There is no information on the impact of the massive antigenic challenge at birth on the mucosal immune system. Well-documented deficiencies in the ability of the blood T cells of the neonate to produce interleukin-4 and interferon-gamma may also occur in the intestine. It is still an open question whether it is better to try to prevent immunological sensitization of the newborn by avoiding potential allergens (i.e. cow's milk), or whether early exposure (as happens when premature infants are given formula feeds) might tolerize the infant. Hydrolysed cow's milk formulae are probably less antigenic than whole cow's milk and have been widely used in the treatment of cow's milk allergy. Some thought is now being given as to whether the prophylactic use of hydrolysates can reduce cow's milk allergy in 'at-risk' infants.
Gastric Mucosa↗
Future role of micronutrients on immune functions.
The future is bright in the field of micronutrients and immunity. New advances in technology now permit the design of many new research studies, and an increased application of the findings to clinical and public health practices. More investigators will need to be trained in the fundamentals of both nutritional and immunological sciences. More basic information will be needed in both fields, but the scientific and clinical values of merging these two fields are already well established. The development of additional animal models will be needed to dissect out the role of each essential micronutrient and its potential importance in each step of the immune response. Based on future studies, new RDAs must be formulated and applied widely in medical and public health practices and in public education.
Animals↗
The impact of psychological stress on immune function in the athletic population.
In many ways, the physiological and immune consequences of acute bursts of physical exercise parallel the effect of an acute psychological stressor. Similarly, the net effects of endurance training resemble chronic psychological stress, whereas the physiological milieu associated with overtraining resembles that of melancholic depression. We suggest that the prolonged psychological stress often associated with athletic training and competition may make athletes more vulnerable to the negative health effects of training. Furthermore, a relationship between anxiety and life events on susceptibility to injury is well documented. Individual differences in self-confidence and self-esteem are also known to relate to the occurrence of injury as well as recovery from injury. We suggest that these two observations may be linked. It is the purpose of this paper to review the most recent evidence that psychological stress does impact upon the balance of the immune system in such a way as to be relevant to health outcomes and that the athletic population, in particular those with low self-esteem, may be especially vulnerable due to the probable synergistic effects of both physical and psychological stress.
Athletic Injuries↗
The HIV-1 accessory gene vpr can inhibit antigen-specific immune function.
The 14-kDa HIV-1 accessory gene vpr has been reported to have effects on host cell biology. These activities include inhibition of cell proliferation, inhibition of NF-kappaB activation, inhibition of CD4 T-cell proliferation, and induction of apoptosis in tissue culture. This collection of activities could, in theory, impact host cell immune responses. We tested the activity of recombinant Vpr protein to inhibit T-cell activation in vitro. Here, we present data illustrating that the Vpr protein can significantly suppress T-cell activation-related cytokine elaboration and proliferation. In vivo, we observed that covaccination with plasmids expressing the vpr gene product profoundly reduces antigen-specific CD8-mediated cytotoxic T lymphocyte (CTL) activity. This supports that vpr might compromise T-cell immunity in vivo during infection. To study this aspect of Vpr biology, we developed an Adenoviral Vpr expression vector for delivery of Vpr to immune cells and to study Vpr function in the absence of other lentiviral gene products. This vector delivers a functional Vpr protein to immune cells including antigen-presenting cells (APCs). We observe that the Adeno-Vpr vector suppresses human CD4 T-cell proliferation driven by immune activation in vitro. Further study of the biology of Vpr will likely have importance for a clearer understanding of host pathogenesis as well as have important implications for HIV vaccine development.
Adenoviridae↗
Inflammatory cell and immune function in Merino sheep with chronic dermatophilosis.
Components of inflammatory and immunological responses were compared in 17 Merino sheep with chronic dermatophilosis (Group 1) and 15 Merino sheep that had recovered from the disease (Group 2). The functions studied included: (i) total and differential white cell counts; (ii) phagocytic function and intracellular killing by neutrophils; (iii) humoral immune response to T-dependent and T-independent antigens and to Dermatophilus congolensis. (iv) lymphocyte blastogenic responses to phytohaemagglutinin; (v) bovine serum albumen and D. congolensis antigens; (vi) quantification of T-lymphocyte subsets in skin lesions resulting after re-infection with D. congolensis zoospores. After all lesions were treated and the sheep were shorn, both groups of sheep were re-infected with D. congolensis. Both groups had similar infection rate, severity of lesions and rate of resolution after re-infection. The Group 2 sheep had significantly higher primary and secondary antibody responses to killed Brucella abortus cells than Group 1 sheep, but Group 1 sheep had higher levels of specific D. congolensis antibody throughout the trial. Neutrophils from Group 1 sheep showed a higher phagocytic rate for D. congolensis zoospores than Group 2 sheep when the zoospores were opsonised by sera from the Group 1 sheep, but there was no difference in their ability to kill ingested zoospores. Although there were some differences between the groups in the proportion of lymphocytes in lesions that reacted with monoclonal antibodies to T4, T8 and T19-19 lymphocyte markers at various times after re-infection, the sheep in Group 2 consistently had higher levels of lymphocytes reacting to a monoclonal antibody for the T6 lymphocyte antigen in skin biopsies collected 9, 15 and 21 days post-inoculation (p.i.) than did sheep in Group 1. Group 2 sheep also had higher levels of epidermal cells with immunohistochemical properties of Langerhans cells at lesion sites 15 and 21 days p.i.
Actinomycetales Infections↗
Effects of exercise stress on various immune functions in horses.
Chemotactic locomotion and luminol-dependent chemiluminescence of neutrophils, mitogen-induced lymphocyte blastogenesis, serum cortisol concentration, immunoglobulin quantification, and leukocyte counts were determined to evaluate the effect of a single strenuous exercise in horses. Increased serum cortisol concentration (P less than 0.01) and an increased neutrophil-to-lymphocyte ratio (P less than 0.05) indicated that horses had been stressed. The chemotactic index and peak chemiluminescence production decreased significantly (P less than 0.05 and P less than 0.01, respectively) 1 day after exercise. Mitogen-induced blastogenesis of lymphocytes and serum immunoglobulin values remained unchanged in response to exercise. Results of this study indicated that a single bout of exercise may transiently impair neutrophil antimicrobial functions and nonspecific defense mechanisms, but not specific immunity in horses.
Animals↗
Antioxidant nutrients and immune functions. Proceedings of the Agricultural and Food Chemistry Division of the American Chemical Society, Symposium on Antioxidant Nutrients and the Immune Response. September 29, 1988, Los Angeles, California.
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Animals↗
Corticosteroids but not pimecrolimus affect viability, maturation and immune function of murine epidermal Langerhans cells.
Given the importance of dendritic cells in the immune response, we investigated the effect of corticosteroids (CS) on the integrity, survival, and function of murine Langerhans cells (LC) in comparison with pimecrolimus, a novel anti-inflammatory drug for the topical treatment of atopic dermatitis. BALB/c mice were treated twice on one day with ethanolic solutions of the compounds. At 24-72 h after the last application, we observed fragmented DNA, caspase-3 activity, and an upregulation of CD95 expression in LC from mice treated with CS but not in LC of pimecrolimus- or vehicle-treated animals. CS-epidermal cell (EC) supernatants but not pimecrolimus-EC supernatants contained significantly lower amounts of soluble factors (GM-CSF, TNF-alpha, IL-1alpha) required for LC survival and maturation than EC supernatants from vehicle-treated mice. With regard to LC maturation, CS but not pimecrolimus inhibited the expression of CD25, CD205, and costimulatory molecules. In line with this, LC from pimecrolimus-treated mice were similar to LC from vehicle-treated mice in their capacity to stimulate antigen-presenting function and migration, whereas LC from CS-treated mice were greatly impaired in these abilities. In summary, our data show for the first time that CS but not pimecrolimus induce apoptosis in LC in situ, implying that the prolonged use of CS could have adverse effects on the skin immune system.
Administration, Topical↗
[Anatomic principles for digestion and immune function in the gastrointestinal tract].
All the cells necessary for the afferent and efferent branch of the immune reaction are present in the intestinal wall. There is a continuous migratory flow of lymphatic cells (MALT = mucosa-associated lymphatic tissue). Experiments in oral immunisation have also recently provided data for clinical use of these migratory paths of IgA precursor cells. The mast cells in the mucosa show heterogeneity and can be differentiated not only by size, life span and origin, but also by the number of granules and the content of mediators. For further research on the cells in the immune system in the wall of the digestive tract new cell markers and functional tests are necessary.
Digestion↗