RESUMO
Dermatophytes invade the stratum corneum of the skin and other keratinized tissues such as hair and nails, and Trichophyton rubrum causes approximately 80% of cutaneous mycoses in humans. To evaluate the cellular immune response of patients with extensive dermatophytosis caused by T. rubrum, we evaluated lymphocyte populations, the lymphoproliferative response to: phytohaemagglutinin (PHA); anti-CD3 (OKT3); and pokeweed mitogen (PWM), Candida sp. (CMA), an extract of T. rubrum, and the main fungal epitope TriR2 (T). We also evaluated interleukin (IL)-4, IL-10, IL-12 and IFN-γ after stimulation by PHA, CMA and TriR2. The immunophenotyping showed no differences between patients and controls. The lymphoproliferation test showed significant differences between the groups stimulated by PWM and CMA, as well as against TriR2, being significantly higher for the control group. Conversely, there were similar results for the groups after stimulation by the extract. The cytokines' quantification showed a significant difference between the groups only for IFN-γ stimulated by PHA and TriR2. We can conclude that the fungal extract can stimulate lymphoproliferation by both groups' lymphocytes. However, the response to Tri r2 was more specific. We showed that some patients with extensive dermatophytosis have normal cellular response, recognising both the extract and TriR2.
Assuntos
Imunidade Celular , Tinha/imunologia , Trichophyton/imunologia , Antígenos de Fungos/imunologia , Candida/imunologia , Estudos de Casos e Controles , Proliferação de Células , Epitopos/imunologia , Seguimentos , Humanos , Imunofenotipagem , Interferon gama/imunologia , Interleucina-10/imunologia , Interleucina-4/imunologia , Ativação Linfocitária , Contagem de Linfócitos , Muromonab-CD3/imunologia , Fito-Hemaglutininas/imunologia , Mitógenos de Phytolacca americana/imunologia , Tinha/microbiologiaRESUMO
BACKGROUND: Atopic dermatitis (AD) is a chronic, inflammatory skin disease with a high prevalence and complex pathogenesis. The skin of AD patients is usually colonized by Staphylococcus aureus (S. aureus); its exotoxins may trigger or enhance the cutaneous inflammation. Several mediators are related to the AD immune imbalance and interleukin-18 (IL-18), an inflammatory cytokine, may play a role in the atopic skin inflammation. AIMS: To evaluate peripheral blood mononuclear cells (PBMC) proliferation response to staphylococcal enterotoxins A (SEA) and B (SEB) and the levels of IL-18 in adults with AD. METHODS: Thirty-eight adult patients with AD and 33 healthy controls were analysed. PBMC were stimulated with SEA and SEB, phytohemaglutinin (PHA), pokeweed (PWM), tetanus toxoid (TT) and Candida albicans (CMA). IL-18 secretion from PBMC culture supernatants and sera were measured by ELISA. RESULTS: A significant inhibition of the PBMC proliferation response to SEA, PHA, TT and CMA of AD patients was detected (P < or = 0.05). Furthermore, increased levels of IL-18 were detected both in sera and non-stimulated PBMC culture supernatants from AD patients (P < or = 0.05). CONCLUSIONS: A decreased PBMC proliferation response to distinct antigens and mitogens (TT, CMA, SEA and PHA) in adults with AD suggest a compromised immune profile. IL-18 secretion from AD upon stimulation was similar from controls, which may indicate a diverse mechanism of skin inflammation maintained by Staphylococcus aureus. On the other hand, augmented IL-18 secretion from AD sera and non-stimulated cell culture may enhance the immune dysfunction observed in AD, leading to constant skin inflammation.
Assuntos
Proliferação de Células/efeitos dos fármacos , Dermatite Atópica/sangue , Enterotoxinas/farmacologia , Interleucina-18/metabolismo , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/patologia , Adolescente , Adulto , Idoso , Candida albicans , Estudos de Casos e Controles , Células Cultivadas , Dermatite Atópica/patologia , Feminino , Humanos , Imunoglobulina E/sangue , Leucócitos Mononucleares/metabolismo , Masculino , Pessoa de Meia-Idade , Fito-Hemaglutininas/farmacologia , Mitógenos de Phytolacca americana/farmacologia , Índice de Gravidade de Doença , Toxoide Tetânico/farmacologia , Adulto JovemRESUMO
Rutin is a flavonoid obtained from Dimorphandra mollis (Benth.), a medicinal Brazilian plant used as antioxidative, antihemorrhagic, and blood vessel protector. The present study has examined its effects on the viability and function of immune system cells in vitro. Rat spleen and thymus cells were cultured with 10 nM, 1 microM, and 10 microM of the drug in the presence or absence of PWM, LPS, or ConA mitogens. Cellular proliferation was analyzed by H(3)-thymidin uptake and IFN-gamma and IL-10 were measured by ELISA after 48 and 72 hr. Viability was measured by flow cytometry using Annexin V and PI after 24 and 48 hr. The flavonoid rutin inhibited splenocytes and thymocytes proliferation under ConA stimulation observed by an increase on apoptosis levels of thymocytes stimulated with PWM in 24 hr and on splenocytes stimulated with PWM in 48 hr. Function studies showed a decrease on IFN-gamma production by splenocytes and thymocytes stimulated with PWM or ConA. Spleen cells cultured with LPS and rutin showed a decrease on apoptosis after 24 hr and an increase on the IL-10 levels after 48 hr. There was no significant variation on the necrosis rate, viability, and function of cells treated with rutin in the absence of mitogenic stimulus.
Assuntos
Sobrevivência Celular/efeitos dos fármacos , Mitógenos/farmacologia , Rutina/farmacologia , Baço/citologia , Linfócitos T/efeitos dos fármacos , Animais , Anexina A5/farmacologia , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Concanavalina A/farmacologia , Citocinas/metabolismo , Interferon gama/biossíntese , Interleucina-10/biossíntese , Lipopolissacarídeos/farmacologia , Masculino , Necrose , Mitógenos de Phytolacca americana/farmacologia , Ratos , Baço/efeitos dos fármacos , Baço/metabolismo , Estimulação Química , Linfócitos T/metabolismoRESUMO
Corynebacterium pseudotuberculosis is the causal agent of caseous lymphadenitis, a chronic illness that attacks goats and sheep characterized by pyogranulomas formation in lymph nodes and organs. Regarding the current knowledge of the pathogenesis of the caseous lymphadenitis, there is evidence that besides the humoral response the induction of a durable cellular response is fundamental for its control. In this sense, research on antigens of C. pseudotuberculosis that are capable to inducing cellular immunity is an important step for the development of diagnosis tests and more efficient vaccines. In the present study, the interferon-gamma production in cultures of whole blood from infected goats stimulated with secreted bacterial antigen or somatic antigen were used to evaluate the cellular response. The results demonstrated a significant difference in the ability of the two antigens to induce a cellular response. That is, IFN-gamma production was high with cells from infected animals in response to the secreted antigen while IFN-gamma production was low when somatic antigen was used. The concomitant use of these antigens with PWM also showed differences. That is, the secreted antigen increased the IFN-gamma production induced by PWM, while the somatic antigen seems not to have altered the response to PWM.
Assuntos
Antígenos de Bactérias/administração & dosagem , Corynebacterium pseudotuberculosis/imunologia , Cabras/imunologia , Interferon gama/biossíntese , Animais , Células Sanguíneas/imunologia , Infecções por Corynebacterium/imunologia , Infecções por Corynebacterium/veterinária , Corynebacterium pseudotuberculosis/patogenicidade , Feminino , Doenças das Cabras/imunologia , Cabras/microbiologia , Técnicas In Vitro , Linfadenite/imunologia , Linfadenite/veterinária , Masculino , Mitógenos de Phytolacca americana/administração & dosagemRESUMO
Zinc and iron are crucial mineral components of human diet, because their deficiency leads to several disorders, including alterations of the immune function. It has been demonstrated, in both humans and rodents, that a diminished number of lymphoid cells and a loss of lymphocyte activity accompany deprivation of these essential minerals. The aim of this work was to analyze if iron and/or zinc imbalances regulate lymphocyte activity and the intracellular signals involved in the effect. Mice from the BALB/c strain were fed with iron- and/or zinc-deficient or mineral-supplemented diets, according to the American Institute of Nutrition Rodent Diets. Levels of iron and zinc were assessed in blood, liver, or bone samples. Selective mitogen stimulation of T- and B-lymphocytes were performed. We found a diminished proliferative response in T- and B-lymphocytes from zinc- and/or iron-deficient animals with respect to controls. These effects were related to decreased mitogen-induced translocation of protein kinase C (PKC) activity to cell membranes on both cell types from all animals fed with deficient diets. Our results demonstrate that iron and zinc deficiencies affect both T- and B-lymphocyte function by PKC-dependent mechanisms.
Assuntos
Linfócitos B/imunologia , Deficiências de Ferro , Proteína Quinase C/fisiologia , Linfócitos T/imunologia , Zinco/deficiência , Animais , Proliferação de Células/efeitos dos fármacos , Concanavalina A/farmacologia , Feminino , Lipopolissacarídeos/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Fito-Hemaglutininas/farmacologia , Mitógenos de Phytolacca americana/farmacologiaRESUMO
BACKGROUND: Chronic renal failure is frequently associated with secondary hyperparathyroidism and immunological disorders. Recent studies support the hypothesis that high levels of parathyroid hormone (PTH) may contribute to the impairment of the cellular and humoral immune response by an immunosuppressive effect on T- and B-cell functions. However, many studies indicate that excess PTH exerts a stimulatory effect on T lymphocytes. Since reports about the immunomodulatory effect of PTH are controversial, our aim was to compare the effect of low and high levels of intact PTH (iPTH) in hemodialysis patients. METHODS: The study was performed on 14 hemodialysis patients with high levels of iPTH (GI), 12 patients with low levels of iPTH (GII) and 13 volunteers (GIII), for whom time of dialysis, iPTH, total number of lymphocytes, B, CD4+, CD8+, lymphoproliferative response to phytohemagglutin (PHA), pokeweed mitogen (PWM) and candidin, IgG and IgM production in vitro in response to PWM, and interleukin (IL)-2 and IL-6 production in vitro in response to PHA were determined. RESULTS: Patients with high iPTH levels had significantly higher responses to PHA than patients with low iPTH. Lymphocyte transformation by PWM and candidin antigen was similar in both groups of patients, but significantly decreased when compared to controls. CD4+ cell counts were significantly increased in GI, and there was a positive correlation between the lymphoproliferative response to PHA and iPTH levels and CD4+ number. CONCLUSION: The present study suggests that high levels of iPTH in hemodialysis patients affect T-cell function, increasing the lympho-proliferative response to PHA and the CD4+ number.
Assuntos
Falência Renal Crônica/imunologia , Hormônio Paratireóideo/sangue , Diálise Renal , Adulto , Alumínio/sangue , Feminino , Humanos , Imunoglobulina G/análise , Imunoglobulina M/análise , Interleucina-2/análise , Interleucina-6/análise , Falência Renal Crônica/sangue , Ativação Linfocitária , Subpopulações de Linfócitos , Masculino , Hormônio Paratireóideo/imunologia , Mitógenos de Phytolacca americana/farmacologiaRESUMO
BACKGROUND/AIMS: Severe secondary hyperparathyroidism is not infrequent in hemodialysis patients and recent studies suggest that parathyroid hormone (PTH) may play a role in the genesis of cell immunity abnormalities in uremia. The aim of the present study is to describe the effect of parathyroidectomy on T- and B-cell functions in hemodialysis patients. METHODS: The study was performed on 6 patients with severe secondary hyperparathyroidism. iPTH, B, CD4(+), CD8(+), total number of lymphocytes, lymphoproliferative response to PHA, PWM and Candidin, and IgG, IgM, IL-2 production in vitro were determined 1 day before and 4 months after parathyroidectomy. RESULTS: The lymphoproliferative response to PHA increased significantly after parathyroidectomy. We also observed a trend to an increase in production of IgG and IgM after PWM stimulation before therapy. CONCLUSION: The present study suggests that patients with extremely high levels of PTH show a complete restoration of impaired T-cell proliferation after parathyroidectomy.
Assuntos
Paratireoidectomia , Diálise Renal , Linfócitos T/imunologia , Adulto , Linfócitos B/imunologia , Divisão Celular/efeitos dos fármacos , Divisão Celular/imunologia , Feminino , Humanos , Hiperparatireoidismo/sangue , Hiperparatireoidismo/imunologia , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Interleucina-2/sangue , Hormônio Paratireóideo/sangue , Fito-Hemaglutininas/farmacologia , Mitógenos de Phytolacca americana/farmacologiaRESUMO
Recurrent infections are common features in patients affected by propionic acidaemia (McKusick 232000) and methylmalonic acidaemia (McKusick 251000). Since these disorders are biochemically characterized by tissue accumulation of propionic acid and methylmalonic acid respectively, it is possible that these compounds may act as immunosuppressants. We therefore investigated the effect of propionate and methylmalonate on cellular growth of human peripheral lymphocytes stimulated in vitro by phytohaemagglutinin, concanavalin A and pokeweed mitogen, a recognized test of cellular immunocompetence. Lymphocytes were cultured in flat-bottomed 96-well microplates at 37 degrees C for 96 h (phytohaemagglutinin and concanavalin A) or 144 h (pokeweed mitogen) in the presence of one mitogen at different concentrations and of one acid added at doses of 1.0, 2.5 or 5.0 mM. Cell blastogenesis was measured by the incorporation of tritiated thymidine into cellular DNA and compared with that of identical cultures with no acid added (controls). A consistent and progressive inhibitory effect of propionic acid with increasing concentrations in culture was identified with all mitogens and was more pronounced with pokeweed mitogen. Lymphocyte blastogenesis was not altered in the presence of methylmalonic acid. The effect of propionate was observed only when the drug was added at the beginning (phytohaemagglutinin-activated) or until 24 h (concanavalin A- and pokeweed mitogen-activated) of culture. The viability of lymphocytes after treatment with the drug, as assessed by the Trypan Blue exclusion test, revealed no change when compared with the same untreated lymphocytes, indicating no lymphocytotoxic activity. In conclusion, propionic acid, which accumulates in tissues of patients with propionic acidaemia, causes 'in vitro' immunosuppression, which may be related to the recurrent infections characteristic of these patients.
Assuntos
Imunossupressores/farmacologia , Ativação Linfocitária/efeitos dos fármacos , Linfócitos/efeitos dos fármacos , Propionatos/farmacologia , Adulto , Células Cultivadas , Concanavalina A/farmacologia , Humanos , Ácido Metilmalônico/farmacologia , Mitógenos/farmacologia , Fito-Hemaglutininas/farmacologia , Mitógenos de Phytolacca americana/farmacologiaRESUMO
Heparinised blood samples were obtained from 20 patients with chronic plaque psoriasis and from 13 age-matched healthy controls. After preliminary titration, mononuclear cells separated over Ficoll-Tryoson were cultured for 5 days with 10 microg ml(-1) of 15 mycobacterial preparations, or with pokeweed mitogen and concanavalin A. Stimulation indices were determined for each reagent and means were determined for patients and controls. Results for patients showed a striking reduction of responsiveness to mycobacteria, apparently due to loss of responses to group i, common mycobacterial antigens, and no differences in responses to mitogens. These observations relate psoriasis to certain other diseases, notably mycobacterial infections, rheumatoid arthritis, Chagas' disease and human immunodeficiency virus infection. The observations may be relevant to the aetiology of psoriasis, and to potential immunotherapy for the disease.
Assuntos
Antígenos de Bactérias/imunologia , Ativação Linfocitária , Mycobacterium/imunologia , Psoríase/imunologia , Linfócitos T/imunologia , Adulto , Células Cultivadas , Concanavalina A/imunologia , Feminino , Humanos , Masculino , Análise por Pareamento , Mitógenos de Phytolacca americana/imunologia , Psoríase/sangueRESUMO
We examined T-cell proliferation in five patients with X-linked hyper-IgM syndrome (XHIM), using a panel of antigens and lectins. All patients had impaired antigen-induced proliferation, whereas their lectin responses were normal. Thus, in addition to severely depressed antibody responses, patients with XHIM have a defect in antigen-specific T-cell proliferation, which may explain their susceptibility to pathogens such as Pneumocystis carinii.