RESUMO
Se presenta evidencias anatómicas, fisiológicas y funcionales que demuestran la interacción entre el sistema nervioso central (SNC), el sistema endocrino y el sistema inmunológico. Igualmente, se demuestra que esta comunicación es bidireccional, y se proporcionan las bases científicas que establecen la comunicación entre el sistema inmune y el SNC. Así mismo, se señala la relación entre el estrés y la respuesta inmune. Por otro lado, presentamos los resultados de nuestro grupo, que demuestran que una intervención psicosocial produce mejorías clínicas, disminución en el consumo de broncodilatadores y modificaciones en la respuesta inmune de niños asmáticos de la Isla de Coche
Assuntos
Humanos , Masculino , Feminino , Asma , Psiconeuroimunologia , Estresse Fisiológico , Medicina , VenezuelaRESUMO
BACKGROUND: Genes linked to the major histocompatibility complex (MHC), have been implicated in atopic asthma. Asthma is highly prevalent in the Venezuelan population (estimated at 20%) and genetic markers are needed to identify populations at risk and plan intervention strategies. OBJECTIVE: To study the influence of the MHC class I and class II genes in the susceptibility to atopic asthma. METHODS: MHC-class I HLA-A, -C, -B and MHC-class II HLA-DR, -DQ, -DP gene haplotype frequencies were determined in 135 Venezuelan mestizos, 71 belong to 20 atopic asthmatic families and 64 unrelated controls. The index cases were 20 atopic asthmatics with positive skin-prick tests and specific serum immunoglobulin E (IgE) for Dermatophagoides pteronyssinus (Der p) and Dermatophagoides farinae (Der f). To ascertain the genes associated with susceptibility to atopy and/or asthma, two control groups were studied, 41 non-atopic subjects with skin-prick negative test, and undetectable levels of specific IgE and 23 non-asthmatic atopic subjects with detectable specific IgE to Der p and Der f. A linkage analysis was performed in those families with two or more atopic siblings (with or without asthma). RESULTS: MHC-class I genes analysis showed that HLA-Cw7 was absent in the asthmatic patients studied, whereas the frequency of this allele was 14.3% in non-atopic controls (P = 0.0 17, PC = 0.19) and 20.8% in the atopic controls (P = 0.0066, PC = 0.07). MHC-class II gene analysis showed a significant increase of the HLA-DRB1*11 in the asthmatic patients compared with non-atopic controls (allele frequencies of 25.6 vs 4.4% P = 0.0017, PC = 0.02). There were no significant differences among asthmatic and atopic controls in the frequency of HLA-DRB1*11 (25.6 vs 17.4%). In contrast, the HLA-DRB1*1101+ haplotypes were significantly higher in asthmatics compared with atopic and non-atopic controls (19.6% vs 2.2% vs 2.3%, PC<0.05). The HLA-DRB1*1101, DQA1*0501, DQB1*0301 haplotype was found significantly increased in the patients vs non-atopic controls (15.4 vs 1.1%, PC< 0.01). The serum levels of specific IgE were detectable in both atopic asthmatics and atopic controls; however, it was higher in atopic asthmatics vs atopic controls Der p (median, 58.7 vs 2.7 kU/L, P<0.001) and Der f (median, 46.9 vs 2.7 kU/L, P<0.001). No linkage between MHC genes and mite-atopy could be documented on informative families with two or more atopic siblings. CONCLUSIONS: We have identified an association between the haplotype HLA-DRB1*1101, DQA1*0501, DQB1*0301 and atopic asthma that confers susceptibility to develop mite-sensitive asthma to atopics (relative risk, RR 8.2), and to non-atopic controls (RR = 15.8) that carry this haplotype. Conversely, the allele HLA-Cw7 was absent in the asthmatics studied and had higher frequencies in the atopic (RR = 0.05) and non-atopic (RR = 0.08) controls. Thus, it may have a protective role for developing atopic asthma in the population studied.
Assuntos
Asma/genética , Asma/imunologia , Adolescente , Adulto , Alelos , Antígenos de Dermatophagoides , Asma/sangue , Criança , Pré-Escolar , Saúde da Família , Feminino , Frequência do Gene , Genes MHC Classe I , Genes MHC da Classe II , Ligação Genética , Glicoproteínas/imunologia , Antígenos HLA-DQ/genética , Cadeias alfa de HLA-DQ , Cadeias beta de HLA-DQ , Antígenos HLA-DR/genética , Cadeias HLA-DRB1 , Haplótipos , Humanos , Imunoglobulina E/sangue , Escore Lod , Masculino , Pessoa de Meia-Idade , Testes Cutâneos , VenezuelaRESUMO
The levels of antibodies of the IgG, IgA and IgM isotypes reacting against ovoalbumin (OVA), gliadin (GL) and cow's milk proteins (CMP), were determined by ELISA in sera from a group of adult patients with sickle cell anemia (SCA) bearing homozygous Ss hemoglobinopathy and from matched health donors. Only patients with steady-state disease were included in the study. Increased amounts of IgG and IgA reacting with OVA, GL and CMP were observed in the group of patients as compared with the controls. In contrast, the levels of IgM antibodies against each of the three dietary antigens were similar in patients and controls. Increased levels of IgG and IgA antibodies against dietary antigens in SCA may result from enhanced permeability of the gut mucosa to macromolecules of dietary origin as a consequence of microinfarctions, chronic polyclonal B cell activation and/or diminished inhibitory control of antibody synthesis.
Assuntos
Anemia Falciforme/imunologia , Anticorpos/sangue , Gliadina/imunologia , Proteínas do Leite/imunologia , Ovalbumina/imunologia , Adulto , Feminino , Humanos , Isotipos de Imunoglobulinas/sangue , MasculinoRESUMO
We have studied the influence of the oral administration of excess copper (Cu) on the immune response. With this aim, mice maintained on standard laboratory diet received 50, 100, 200, or 300 ppm of Cu as copper sulfate in the drinking water during 3 to 10 weeks. Inhibition of the proliferative response to concanavalin A was observed in mice exposed to 100 ppm of Cu for 8 weeks and to 200 ppm of Cu for either 3 or 8 weeks. Conversely, a significant increase in the proliferative response to Escherichia coli lipopolysaccharide (LPS) was observed in mice exposed to 50 or 100 ppm of Cu for 3 weeks. However, the response to LPS was also significantly inhibited following prolonged Cu administration. In contrast, mice exposed to low or high Cu doses during short or long periods showed increased production of autoantibodies directed to bromelain-treated mouse erythrocytes. The DTH response to sheep red blood cells was not modified following short-term administration of 100 ppm of Cu, but was depressed after prolonged exposure to this dose of the metal. Significant inhibition of the DTH response was observed in mice exposed to 300 ppm of Cu for 5 or 10 weeks. Thus, oral administration of excess Cu altered the immune response in a fashion related to the dose and duration of treatment.
Assuntos
Cobre/intoxicação , Sistema Imunitário/efeitos dos fármacos , Administração Oral , Animais , Formação de Anticorpos/efeitos dos fármacos , Autoanticorpos/biossíntese , Sulfato de Cobre , Eritrócitos/imunologia , Feminino , Hipersensibilidade Tardia/imunologia , Ativação Linfocitária/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mitógenos/farmacologiaRESUMO
To study if treatment with zinc (Zn) was able to restore to normal levels the depressed immune response determined by oral administration of excess copper (Cu), groups of mice receiving 100 ppm or 200 ppm of Cu in the drinking water for 8 weeks, were injected ip once a week with Zn (1.14 mg/kg of body weight), throughout the experimental period. Administration of Zn restored to normal levels the proliferative response to mitogens and the antibody response to sheep red blood cells in the group of mice receiving 100 ppm of Cu in the drinking water. Similarly, the treatment with Zn significantly enhanced the depressed proliferative response to mitogens and the antibody response to sheep red blood cells of mice receiving 200 ppm of Cu in the drinking water. By contrast, increment in Zn supply was not able to modify the high production of auto-antibodies observed in animals receiving excess Cu. The results suggest that the impairment of the immune response observed in animals receiving excess Cu could be in part due to antagonistic interactions between this cation and Zn.
Assuntos
Cobre/toxicidade , Imunidade/efeitos dos fármacos , Zinco/farmacologia , Administração Oral , Animais , Formação de Anticorpos/efeitos dos fármacos , Autoanticorpos/biossíntese , Cobre/administração & dosagem , Feminino , Ativação Linfocitária/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Zinco/deficiênciaRESUMO
We have studied the influence of different degrees of calorie restriction on the induction and the regulation of the delayed type hypersensitivity (DTH) response to trinitrobenzenesulfonic acid (TNBS) and TNBS-modified spleen cells (TNBS-SC), injected by the sc or the iv route. Immediately after weaning, BALB/c mice were placed on restricted diets for either 2 or 4 weeks and then the DTH response was induced. The results showed that a 37.5% restriction in the food supply significantly depressed the level of the DTH response induced by the sc injection of TNBS-SC. In contrast, a 25% restriction in the food supply was insufficient to depress the response. Calorie restriction did not modify the inhibitory influence of an iv injection of TNBS-SC on the DTH response. However, iv presensitization with free hapten or the simultaneous injection of TNBS-SC by the iv and the sc routes did not significantly depress the DTH response in calorie-restricted mice, indicating a defect in the inhibitory regulation of the DTH response in these dietary groups.
Assuntos
Dieta Redutora , Haptenos , Hipersensibilidade Tardia , Nitrobenzenos , Ácido Trinitrobenzenossulfônico , Animais , Peso Corporal , Feminino , Imunização , Linfócitos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Baço/imunologia , Fatores de TempoRESUMO
C57BL/6 mice infected with Leishmania mexicana showed depression of the in vitro immunoglobulin M-plaque-forming cell response to sheep erythrocytes. Immunodepression was present 3 weeks after inoculation and was maximal at 11 weeks. Thereafter, there was a gradual return to normal immunoresponsiveness correlated with the resolution of lesions. At the time of maximal immunodepression, spleen cells from infected mice diminished the plaque-forming cell response to sheep erythrocytes of normal spleen cells. On the other hand, specific responses, as exemplified by protective immunity to a challenge infection and delayed hypersensitivity responses to parasite antigens, were apparently unaffected. These responses were both present in mice bearing primary lesions and were maximal in recovered mice. The significance of these findings is discussed in relation to a current hypothesis on parasite-induced immunodepression.