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Immune functions of the human skin. Models of in vitro studies using Langerhans cells.

Human skin constitutes the first immune defense barrier. Among the epidermal cells, the Langerhans cells, which belong to the dendritic cells, represent the pivotal cells in cutaneous immune reactions. The possibility of obtaining human Langerhans cells either from human skin or by in vitro generation from CD34+ hematopoietic precursors opens the way to studies reproducing the successive steps of the Langerhans cells' role in contact dermatitis.

Cytokines↗

Effect of dietary intake on immune function in athletes.

Athletes are exposed to acute and chronic stress that may lead to suppression of the immune system and increased oxidative species generation. In addition, the tendency to consume fewer calories than expended and to avoid fats may further compromise the immune system and antioxidant mechanisms. The exercise stress is proportional to the intensity and duration of the exercise, relative to the maximal capacity of the athlete. Muscle glycogen depletion compromises exercise performance and it also increases the stress. Glycogen stores can be protected by increased fat oxidation (glycogen sparing). The diets of athletes should be balanced so that total caloric intake equals expenditure, and so that the carbohydrates and fats utilised in exercise are replenished. Many athletes do not meet these criteria and have compromised glycogen or fat stores, have deficits in essential fats, and do not take in sufficient micronutrients to support exercise performance, immune competence and antioxidant defence. Either overtraining or under nutrition may lead to an increased risk of infections. Exercise stress leads to a proportional increase in stress hormone levels and concomitant changes in several aspects of immunity, including the following: high cortisol; neutrophilia; lymphopenia; decreases in granulocyte oxidative burst, nasal mucociliary clearance, natural killer cell activity, lymphocyte proliferation, the delayed-type sensitivity response, the production of cytokines in response to mitogens, and nasal and salivary immunoglobulin A levels; blunted major histocompatibility complex II expression in macrophages; and increases in blood granulocyte and monocyte phagocytosis, and pro- and anti-inflammatory cytokines. In addition to providing fuel for exercise, glycolysis, glutaminlysis, fat oxidation and protein degradation participate in metabolism and synthesis of the immune components. Compromising, or overusing, any of these components may lead to immunosuppression. In some cases, supplementation with micronutrients may facilitate the immune system and compensate for deficits in essential nutrients. In summary, athletes should eat adequate calories and nutrients to balance expenditure of all nutrients. Dietary insufficiencies should be compensated for by supplementation with nutrients, with care not to over compensate. By following these rules, and regulating training to avoid overtraining, the immune system can be maintained to minimise the risk of upper respiratory tract infections.

Dietary Carbohydrates↗

Immune function and adjustment style: do they predict survival in breast cancer?

The aim of this study was to investigate the role of immune status and psychosocial factors in survival from early breast cancer (N=61). Baseline assessments included lymphocyte number and function, natural killer cell activity (NKA), plasma cortisol and prolactin level. Psychosocial measures included anxiety, depression and mental adjustment to cancer and social support. Length of follow-up was 6.1-7.9 years with 14 (23%) breast cancer deaths. In Cox proportional hazards models adjusting for lymph node status two parameters predicted longer survival, low NKA (HR 29 per LLU, p=0.003) and minimizing the illness adjustment (HR 0.64 per scale point, p=0.012). These data provide little evidence for a psychoneuroimmunological mechanism in the survival from breast cancer. While this study is limited due to small sample size, and therefore the possibility of inflated estimates, longer survival in those minimizing the illness is a finding consistent with recent studies; however, the counter-intuitive finding that high NKA predicts shorter survival may be a marker for current disease or response to treatments.

Adaptation, Psychological↗

Season- and gender-dependent changes in the immune function of Siberian hamsters (Phodopus sungorus).

OBJECTIVES: Siberian hamsters are photoperiodic animals exhibiting seasonality of reproduction and other physiological functions. Thus, the influence of photoperiod on the in vitro activity of selected immune cells from male and female hamsters challenged with peritoneal inflammation was examined. METHODS: Animals were housed for 8-10 weeks in LD (L:D=18:6) or SD (L:D=6:18). Peritoneal leukocytes (PTLs) and splenocytes were isolated form male and female and testicular macrophages (TMs) from male hamsters, intact or challenged with zymosan-induced peritonitis. PTL and TM activity was assessed by the level of reactive oxygen species (ROS) measured with the use of flow cytometry and splenocyte activity -- by the spontaneous and mitogen-stimulated proliferation measured with the use of 3H-tymidine incorporation test. RESULTS: Results obtained indicate that the immune system of Siberian hamsters is highly sexually dimorphic. Experimentally evoked peritonitis developed differently in males and females: only in LD male hamsters an increase in PTL activity was observed after zymosan treatment. Also, in LD males, PTL activity was higher in LD than in SD. Developing peritonitis exerted in these animals a stimulatory effect on splenocyte proliferation but had no influence on cells residing in the immune privileged testes. Splenocyte proliferation, both spontaneous and PHA-stimulated, depended on the photoperiod studied: in LD it was significantly higher than in SD in animals of both sexes. CONCLUSIONS: Innate immunity of Siberian hamsters studied on the peritoneal inflammation model, seems to be gender- and photoperiod dependent. Moreover, local inflammation may affect other lymphoid organs but does not influence immune-privileged sites.

Animals↗

UVB irradiation suppresses cytokine production and innate cellular immune functions in mice.

We examined whether ultraviolet-B (UVB) irradiation (6 kJ/m2) alters cytokine production and other innate immune reactions by murine peritoneal macrophages and peripheral neutrophils. Along with these experiments, serum IgG levels were also assessed. In addition, using scanning electron microscopy (SEM) we observed macrophages that had been exposed to UVB in vitro. Results showed that UVB irradiation: (1) decreased IL-12 production while increasing IL-1alpha secretion from macrophages, but had no effect on IL-1alpha from neutrophils; (2) suppressed phagocytosis of macrophages but not of neutrophils; (3) diminished active oxygen production of macrophages but not of neutrophils; (4) had no effect on serum IgG levels; and (5) caused significant cell destruction of macrophages in vitro. These results suggested: (1) that UVB irradiation could induce characteristic suppression of innate immunity; (2) that innate cellular immunity was more susceptible to the effects of UVB irradiation than humoral immunity.

Animals↗

Liver sinusoidal lymphocytes: their immune functions.

Recent studies strongly suggest that the liver plays an important immunoregulatory role. Evidence of its role in general immune responsiveness originates from observation that, in recipients of liver grafts, the survival of other allografts is significantly prolonged. The question arises as to which blood lymphocyte subsets, most likely to be responsible for this phenomenon, marginate in liver sinusoids. To study this problem, a liver ex vivo perfusion model was designed for rats. In situ W/WAG livers were washed clear of sinusoidal marginating cells prior to and after 1 h perfusion with syngeneic blood. The number of blood cells retained in liver sinusoids, their phenotypes, the responsiveness to mitogen (PHA, 90 micrograms/ ml) and cytotoxicity against YAC-1 tumour cells were examined. Our studies showed that rat liver retains in the sinusoids a population of blood cells, enriched in NK, CD8+ and MHC class II+ cells, displaying a high cytotoxic activity and low responsiveness to mitogen stimulation, with a capacity of about 10(6) cells/g of tissue.

Animals↗

Immune functions in Parkinson's disease lymphocyte subsets, concanavalin A-induced suppressor cell activity and in vitro immunoglobulin production.

Immune abnormalities, including the occurrence of autoantibodies against neural structures, diminished numbers of peripheral blood lymphocytes and reduced mitogen responses have been observed in patients with Parkinson's disease. In this study, we found that among the peripheral blood mononuclear cells (PBMNC) of patients with Parkinson's disease, there is a reduced number of cells spontaneously secreting immunoglobulins (Ig). After pokeweed mitogen stimulation, PBMNCs from patients with advanced Parkinson's disease had decreased capacity to elaborate Igs in vitro. In addition, there was evidence suggesting that OKT4+ (helper/inducer) subset may be decreased in Parkinson's disease along with disordered concanavalin A-induced suppressor cell activity. The findings do not primarily suggest an autoimmune pathogenesis of Parkinson's disease. The immune changes now observed partially resemble those seen in normal ageing, though being quantitatively exaggerated in Parkinson's disease. It is suggested that immune abnormalities in Parkinson's disease may result from disordered neural-immune regulation.

Aged↗

Cyclophosphamide-induced changes in the MRL-lpr/lpr mouse: effects upon cellular composition, immune function, and disease.

MRL-lpr/lpr mice develop massive lymphadenopathy with excessive proliferation of T cells and associated immune abnormalities. To examine whether to not the disease process is intrinsic and irreversible, an immunomodulatory drug, cyclophosphamide, was administered to 16-week-old, sick MRL-lpr/lpr mice. Analysis of lymph node cells by flow cytometry from injected and control MRL-lpr/lpr mice indicated that cyclophosphamide had a marked effect upon the lymphoid cellular composition. Whereas control lymph nodes had a very large number of abnormal dull Ly 1+ T cells and very few other cells, the cyclophosphamide-injected mice had normal T and B cells. The immune responses to a T-cell-dependent antigen, sheep red blood cells, and a T-cell mitogen, concanavalin A, were normalized in cyclophosphamide-injected mice as compared to controls. In addition, injected mice had prolonged survival, decreased arthritis, markedly reduced adenopathy and splenomegaly, improved renal histology, and significantly diminished autoantibody levels. This study suggests that the disease and associated immune abnormalities of MRL-lpr/lpr mice are reversible by selective elimination of the abnormal dull Ly 1+ T cells.

Animals↗

The use of human leucocyte antigen class I transgenic mice to investigate human immune function.

HLA class I transgenic mice are a powerful research tool which have been used as models for human immune responses. This review describes the generation of the different HLA class I transgenic mice, the techniques used to improve expression of the transgene and use of the transgene product in immune responses. It also illustrates how HLA class I transgenic mice have provided insights into the nature of the allogeneic and xenogeneic response, the generation of CTL responses, the development of autoimmune diseases, and their use for the generation of anti-HLA class I antibodies. Despite these advances, the use of available HLA class I transgenic mice as models for human disease and immune responses has been limited. The development of new transgenic strains incorporating multiple human transgenes may allow the potential of HLA class I transgenic mice to be realised.

Alleles↗

Immunomodulatory effects of linomide in animals immunized with immunopathogenic retinal antigens: dissociation between different immune functions.

Linomide (LS-2616, quinoline-3-carboxamide) has been reported to exert a diverse range of effects on the immune system. On one hand, this drug was found to stimulate the immune system and to enhance activities such as DTH or allograft rejection. On the other hand, linomide was shown to inhibit the induction of experimental autoimmune encephalomyelitis and myasthenia gravis, as well as the development of diabetes in non-obese diabetic (NOD) mice. Here we report the effects of linomide in animals immunized with uveitogenic retinal antigens. Treatment with linomide completely inhibited the development of experimental autoimmune uveoretinitis (EAU) in mice immunized with interphotoreceptor retinoid-binding protein and markedly suppressed EAU in rats immunized with S-antigen (S-Ag). In addition, linomide-treated rats exhibited reduced antibody production and lymphocyte proliferative response to S-Ag. In contrast to these suppressive activities, linomide treatment did not affect the development of adoptively transferred EAU in rats and moderately enhanced the DTH reactions to S-Ag in immunized rats in which EAU and other immune responses to this antigen were suppressed.

Adjuvants, Immunologic↗

Effects of experimental hyper- and hypothyroidism on numbers of blood mononuclear cells and immune function in rats and guinea-pigs.

A possible effect of thyroid hormones on numbers of mononuclear cells and immune reactivity has been studied in hyperthyroid and hypothyroid guinea-pigs and rats. There were no major changes in populations of blood mononuclear cells in hyperthyroid or hypothyroid animals compared with populations in euthyroid animals. Although there was some evidence for depressed cell-mediated responses to an extract of Candida (monilia) albicans in hyperthyroid rats as assessed by skin tests, this was minor, and responses in tuberculin purified protein derivative (PPD) were normal in all groups, whilst production of macrophage migration inhibition factor in response to PPD and Candida was similar in the three groups of animals. Antibody responses to sheep red blood cells, a thymic-dependent antigen, tended to be depressed in hyperthyroid and hypothyroid rats and increased in hyperthyroid and hypothyroid guinea-pigs, although this was significant only for hyper-thyroid guinea-pigs 16 days after immunization. Responses to trinitrophenol-Ficoll, a thymic-independent antigen, were similar to the three groups of guinea-pigs. Thus, a major effect of excess or deficiency of thyroid hormone on immune responses to foreign antigens has not been demonstrated, although it is possible that immune reactions against thyroid antigens may be more sensitive to the effect of thyroid hormones than responses to foreign antigens.

Animals↗