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Dietary lipids and immune function.

Interest in the use of alternative dietary lipids to prevent or control human disease has gained scientific support from numerous studies which have uncovered beneficial effects of increased amounts of polyunsaturated fish and plant oils upon such diverse disease processes as atherosclerosis and coronary heart disease, rheumatoid arthritis, post-operative and post-traumatic recovery, and sepsis. The immunologic processes which underly these pathologic states, and the possible ways in which dietary lipids may influence immunologic function are areas of active research. This review aims to summarize the current views of understanding how immune-mediated processes and inflammatory states may be altered by the content and types of lipids in the diet.

Animals↗

Susceptibility to infections and in vitro immune functions in cartilage-hair hypoplasia.

UNLABELLED: Cartilage-hair hypoplasia (CHH), an autosomal recessive chondrodysplasia, results in severe growth failure, sparse hair and impaired cellular immunity. Lymphocyte subpopulations and proliferative responsiveness in mitogen stimulation were analysed in 35 patients of whom 31% had an increased incidence of infections the year prior to the evaluation. Of the patients, 57% had a decreased CD4+ cell count which led to a decreased total count of T-lymphocytes in 52% and a subnormal CD4 +/CD8 + cell ratio in 32%. The B-lymphocyte count was usually normal. The natural killer cell count was above reference values in 40% of the patients. The lymphocyte stimulation indices as studied with phytohaemagglutinin , Concanavalin A and pokeweed mitogen were subnormal in 69%, 69% and 83% of the patients, respectively. The numbers of lymphocytes, T-lymphocytes and CD4+ cells, and the pokeweed mitogen stimulation index. but not the other measured parameters, correlated significantly with the proness to infections during the preceding year. However, the correlation was reverse with higher counts in the patients who had had recurring infections. The observed significant correlations may reflect immunological stimuli caused by recurring infections. CONCLUSION: The presently used parameters of cellular immunity poorly predict the clinical outcome of an individual cartilage-hair hypoplasia patient. All patients, irrespective of their in vitro immunological competence, have to be carefully followed because of possibility of serious infections and malignancies.

Antigens, Surface↗

Effects of O,S,S-trimethyl phosphorodithioate on immune function.

The effect of acute administration of 20-80 mg/kg O,S,S-trimethyl phosphorodithioate (OSS-TMP) to C57BL/6 female mice on the murine immune system was determined. The parameters examined to evaluate overt toxicity of the compound included body weight, plasma cholinesterase levels, splenic nucleated cell number and thymic weight and nucleated cell number. Acute administration of 60 or 80 mg/kg OSS-TMP led to a 75 or 63% decrease, respectively, in plasma cholinesterase levels and a decrease in thymic size. At a dose of 80 mg/kg OSS-TMP, the animals also exhibited some lethargy and body weight loss. Below 60 mg/kg OSS-TMP, no overt toxic manifestations were observed. These studies were carried further to determine the effect of OSS-TMP on the generation of in vivo primary and in vitro secondary cellular and humoral immune responses. At nontoxic doses of the compound, i.e. 20 and 40 mg/kg OSS-TMP, the in vivo generation of a primary cytotoxic T lymphocyte (CTL) response to alloantigen was significantly elevated, but this response was unaffected following restimulation of the splenocytes by alloantigen in vitro. The generation of an in vivo primary and in vitro secondary humoral responses to sheep red blood cells (SRBC) was elevated following a single dose of 40 mg/kg OSS-TMP. Administration of toxic doses of OSS-TMP, i.e. 60 and 80 mg/kg, did not alter the ability of splenocytes to generate a primary or secondary CTL response, but suppressed the generation of humoral immune responses. These results differ significantly from those observed in a similar system following acute administration of a structural analog, O,O,S-trimethyl phosphorothioate which was previously shown to have potent immunosuppressive activity at nontoxic doses.

Animals↗

Glucocorticoid resistance and the immune function in the immunodeficiency syndrome.

Glucocorticoids, the final product of HPA axis, and their receptors (GRs) on mononuclear cells are crucial mediators in the endocrine-immune interaction. An alteration in GRs involving a lower receptor affinity (Kd) for glucocorticoids has been found in a group of advanced AIDS patients, who developed Addisonian symptoms (weakness, weight loss, hypotension, hyponatremia, and intense mucocutaneous melanosis) in spite of hypercortisolism and normal or slightly elevated values of ACTH (AIDS-GR). In these patients, data for the suppression test showed decreased cortisol and ACTH suppression in response to exogenous dexamethasone. The inhibitory effect of dexamethasone on radiolabeled-thymidine incorporation in mononuclear cells from these patients was also reduced. Monocytes of AIDS-GR patients had a receptor Kd of 10.5 +/- 4.2 nmol/l that was higher than that of other AIDS patients (AIDS-C) (2.9 +/- 0.8 nmol/l) and normal subjects (2.0 +/- 0.8 nmol/l: p < 0.01). Correlations were found between plasmatic IFN-alpha and receptor Kd on monocytes of AIDS-GR (r = 0.77). Poly (i)-poly (c)-induced IFN-alpha production by monocytes was inhibited by glucocorticoids in the AIDS-C group and controls (approx. 80% in both groups): The effect was reversed by the receptor antagonist RU-486. By contrast, glucocorticoid did not inhibit IFN-alpha production in AIDS-GR group. In conclusion, levels of plasmatic IFN-alpha, a cytokine with antiviral properties, may be increased several times, and dexamethasone fails to inhibit monocytes' IFN-alpha production only in AIDS with cortisol resistance, a disturbance that confirms an important immunoregulatory role of glucocorticoids in HIV disease.

Acquired Immunodeficiency Syndrome↗

Effects of mind-body therapy on quality of life and neuroendocrine and cellular immune functions in patients with ulcerative colitis.

BACKGROUND: The aim of this study was to investigate the effects of mind-body therapy on neuroendocrine and cellular immune measures, health-related quality of life and disease activity in patients with ulcerative colitis (UC) in remission. METHODS: Thirty UC patients in remission or with low disease activity were randomly assigned to an intervention group (n = 15) or a usual-care waiting control group (n = 15). Intervention consisted of a structured 60-hour training program over 10 weeks which included stress management training, moderate exercise, Mediterranean diet, behavioral techniques and self-care strategies. Quality of life, perceived stress and disease activity were assessed with standardized questionnaires (IBDQ, SF-36, PSS, CAI). In addition, the distribution of circulating lymphocytes and lymphocyte subsets as well as the beta-adrenergic modulation of TNF-alpha production in vitro were analyzed. Urine catecholamines and plasma cortisol, prolactin and growth hormone were measured pre- and postinterventionally, and were compared with a healthy control group (n = 10). RESULTS: In response to therapy, patients in the intervention group showed significantly greater improvement in the SF-36 scale Mental Health and the Psychological Health Sum score compared with changes observed in the usual-care waiting control group. Patients in the intervention group showed significantly greater improvement on the IBDQ scale Bowel Symptoms compared with the control group. However, no significant group differences in circulating lymphocyte subsets or endocrine parameters were observed in response to therapy. In addition, no significant effects of intervention on either the basal levels of TNF-alpha or the suppressive action of the beta-adrenergic agonist isoproterenol on TNF-alpha production were observed. CONCLUSION: Mind-body therapy may improve quality of life in patients with UC in remission, while no effects of therapy on clinical or physiological parameters were found, which may at least in part be related to selective patient recruitment.

Adult↗

Effect of a mono-specific algal diet on immune functions in two bivalve species--Crassostrea gigas and Ruditapes philippinarum.

The impact of diets upon the fatty acid composition of haemocyte polar lipids and consequently upon immune parameters has been tested in the oyster Crassostrea gigas and the clam Ruditapes philippinarum. Oysters and clams were fed each of three cultured algae: Chaetoceros calcitrans, which is rich in 20:5(n-3) and 20:4(n-6) and poor in 22:6(n-3) fatty acids; T-Iso (Isochrysis sp.), which is rich in 22:6(n-3) and deficient in 20:5(n-3) and 20:4(n-6); and Tetraselmis suecica, which is deficient in 22:6(n-3) and contains only small amounts of 20:5(n-3) and 20:4(n-6). Fatty acid composition of haemocyte polar lipids was greatly affected by the diet. Oysters and clams fed C. calcitrans maintained a higher proportion of 20:5(n-3) and 20:4(n-6) in their haemocyte polar lipids, while these polyunsaturated fatty acids decreased drastically for animals fed T-Iso. However, the T-Iso diet maintained 22:6(n-3) in haemocyte polar lipids of both species. Higher 20:5(n-3) and 20:4(n-6) contents in diets appeared to have a positive effect upon total haemocyte count, granulocyte percentage, phagocytic rate and oxidative activity of clam haemocytes. Similarly, a positive effect of 20:5(n-3) on oxidative activity of oyster haemocytes was observed but to a lesser extent than in clams. Interestingly, when oyster haemocytes are submitted to a stressful condition, a positive effect of a higher dietary 22:6(n-3) content on the phagocytic rate was noticed.

Analysis of Variance↗

Vitamin E enhances the immune functions of young but not old mice under restraint stress.

Young and old C57BL/6 male mice were given a diet containing a high dose of vitamin E (VE treatment) and its effect on the immune system was examined before and after the exposure to restraint stress. The VE treatment per se gave rise to a slight increase of splenic T cells in percentage and a significant enhancement of Con A response of spleen cells in young, but not in old mice. The VE treatment also resulted in the enhancement of production of IL-2 and IFNgamma in young, but not in old mice. Restraint stress led to thymic involution in both young and old mice. This thymic involution was not ameliorated by the VE treatment. Percentage of splenic T cells and their mitogenic response decreased just after the stress, but soon rebounded over the control level. The VE treatment further enhanced the recovery after the stress in young mice, but on the contrary suppressed the recovery in old mice. The results in the present study suggested that the VE treatment was effective in the prevention of immunological decline of young mice before and after the exposure to the stress. On the other hand, such a preventive effect was not observed in old mice that were already in the depressed state of immunological functions.

Aging↗

Placental Site Trophoblastic Tumor Acquires Immune Functions by Incorporating Host Maternal Genes.

Although it was proposed that cell fusion of cancer cells with leukocytes creates mobile hybrids with a metastatic phenotype, it has been difficult to genetically confirm cell fusion events in human cancer in vivo. Here, we experienced 4 cases of placental site trophoblastic tumor (PSTT) that produced immunoglobulin (Ig). Three cases showed recurrence and responded well to pembrolizumab therapy. Among them, we could analyze temporal changes in the genetic profiles on one case of daughter-derived PSTT, which relapsed after pembrolizumab therapy. In this case, we found that PSTT incorporated the exogenous genes from host maternal cells. The rearrangement patterns of Ig genes and protein expressions sequentially increased. By analyzing single-nucleotide variants, PSTT incorporated daughter-non-inherited maternal alleles (DNIMA), including the Ig lambda and HLA-DQA2 loci. Protein expressions of TLR10 and SIGLEC10 increased during tumor progression concomitantly with DNIMA incorporation. DNIMA mapping indicates the incorporation of exogenous maternal genes was widely distributed through the whole chromosomes, suggesting the involvement of cell fusion in gene transfer mechanisms. These findings indicate that PSTT sequentially incorporated exogenous genes from maternal cells to express immune-related molecules and suggest that cancer cells acquired B cell-related functions, including Ig production by cell fusion with host immune cells.

Humans↗

Relationship of social support to stress responses and immune function in healthy and asthmatic adolescents.

Although most clinicians believe that social support has beneficial effects on health, the mechanisms mediating this relationship have not been clearly established. We examined the direct effect of social support on several immune measures and its role in moderating the response to academic exams in healthy and asthmatic adolescents. Three types of students--healthy, mild asthma, and severe asthma--completed social support and stress questionnaires and gave blood samples during the midsemester and final exam periods. Social support and natural killer cell (NK) function showed a significant reduction during exams in both healthy and asthmatic adolescents. Social support, however, did not have a direct effect on immune responses. Nevertheless, high social support appeared to attenuate the magnitude of exam-induced reduction in NK activity, suggesting a role for social support in protecting against immune decrements during times of stress.

Adolescent↗

Tumor-derived factors impaired motility and immune functions of dendritic cells through derangement of biophysical characteristics and reorganization of cytoskeleton.

The generation and progress of tumors are accompanied with a marked suppression of human immune system. To explore the mechanisms by which tumors escape from immune recognition, we studied the influences of tumor microenvironment on differentiation of dendritic cells (DCs), which play an important role in tumor immunology, by biophysical and immunological methods. It was found that the cytokines derived from tumors caused an increase in osmotic fragility and a decrease in membrane fluidity of DCs, disordering and elevated expression levels of cytoskeleton, and changes of the gene transcriptional levels and energy status of the cells. Moreover, IL-12 production and the expression levels of some surface-marker molecules were also suppressed. These changes led to impaired capabilities of antigen uptake, cell motility and naïve T cell activation; the abnormal biophysical characteristics of DCs may be one aspect of the immune escape mechanism of tumor. These results provide insights into the importance of the reconstruction of tumor microenvironment for immunotherapy based on the anti-cancer activities of DCs.

Actins↗

Immune functions of murine alveolar macrophages: binding of lymphocytes and support of lymphocyte proliferation.

Interactions between alveolar macrophages and lymphocytes may be important in the generation of pulmonary immune responses or in the induction of immunologic lung disease. We compared the relative abilities of normal murine alveolar macrophages and peritoneal macrophages to bind primed lymphocytes and to support antigen-induced lymphocyte proliferation. Alveolar macrophages were obtained by lung lavage and peritoneal macrophages by peritoneal lavage of normal mice. Lymph-node cells were harvested from draining lymph nodes of mice immunized with the peptide antigen (T,G)-A-L. Lymph-node cells were depleted of macrophages by passage through columns of Sephadex G-10 and nylon wool. To study the binding of lymphocytes to macrophages, lymph-node cells were layered over antigen-pulsed alveolar and peritoneal macrophage monolayers and the number of lymphocytes bound to the macrophages counted microscopically after incubation for 1-20 hr. Macrophage support of antigen-induced lymphocyte proliferation was studied by 3H-thymidine uptake of macrophage-depleted primed lymph-node cells cultured in the presence of soluble antigen. Cultures were repleted with graded percentages of alveolar or peritoneal macrophages. The results showed that alveolar macrophages bound significantly fewer lymphocytes than peritoneal macrophages both in a nonspecific and an antigen-specific manner. The difference in lymphocyte-binding affinity between the two macrophage types could not be attributed to factors present in lung lavage fluid. Results of the lymphocyte proliferation studies showed that while alveolar macrophages were able to support lymphocyte proliferation in response to antigen, they did so less effectively than an equal number of peritoneal macrophages. We conclude that alveolar macrophages differ significantly from peritoneal macrophages in their ability to interact with lymphocytes, both with respect to lymphocyte binding and in support of lymphocyte proliferative responses.

Animals↗

Immune function in pheasants experimentally infected with marble spleen disease virus.

Two experiments were conducted to evaluate the effect of marble spleen disease virus (MSDV) infection on the immune response of pheasants. In the first, 15 ring-necked pheasants were inoculated orally with cell-culture-propagated MSDV and 15 received saline (controls). On days 7, 21, and 35 postinoculation (PI), all birds received sheep erythrocytes intravenously. Hemagglutination titers to sheep erythrocytes were determined for serum samples collected weekly for 6 weeks. The virus-inoculated group had significantly (P less than 0.05) lower hemagglutination titers than the control group. In the second experiment, 30 pheasants were allotted into two groups as above. Whole blood was collected from each bird weekly for 5 weeks. The blood was cultured in microtiter plates with or without optimum concentrations of concanavalin A. Five of 10 MSDV-inoculated pheasants had significantly depressed T lymphocyte transformation on either day 7 or day 14 PI. Overall, the depression of T lymphocyte transformation was transient and mild.

Adenoviridae Infections↗

[Ultraviolet rays and the skin. Modulation of immune functions].

Ultraviolet radiations (UV) are one of the most common environmental stimuli. In the skin, UVs induce selective biological alterations whose effects include suppression of the normal immune response. This immune suppression may play an important part in the development of skin cancers, infectious diseases, and autoimmune responses. The review presented here focuses on UV-induced biological disorders and on the role of UV-exposed epidermal cells in the mechanisms of immunosuppression.

Adjuvants, Immunologic↗