RESUMO
Based on a unifying theory presented here, it is predicted that the immune defects resulting in chronic inflammation rather than effective immune responses could be rectified by the therapeutic use of agents prepared from micro-organisms. With appropriate molecular patterns, these should be able to induce protective immunoregulatory networks or to reprogramme defective ones. In contrast to acute inflammation, chronic inflammation appears to have no beneficial role, but is a state of sustained immune reactivity in the presence or progression of a disease process. This results in an escalating cycle of tissue damage followed by unproductive tissue repair, breaks in self-tolerance, malignant transformation or deleterious changes in tissue morphology and function. Such inappropriate immune reactivity is an underlying characteristic, either in initiation or maintenance, of a diverse range of disease states including chronic infection, autoimmunity, allergy, cancer, vascular disease and metabolic alterations. Evidence is presented that the inappropriate immune reactivity is due, at least to some extent, to failures in the establishment of immunoregulatory networks as a result of hygiene-related factors. Such networks are the result of activation of antigen-presenting cells, principally dendritic cells, by molecular patterns of micro-organisms encountered sequentially during life and establishing the 'biography' of the immune system.
Assuntos
Produtos Biológicos/uso terapêutico , Inflamação/imunologia , Animais , Autoimunidade/imunologia , Produtos Biológicos/imunologia , Doença Crônica , Células Dendríticas/imunologia , Progressão da Doença , Humanos , Infecções/imunologia , Infecções/terapia , Inflamação/terapiaRESUMO
The well-established model of Chagas' disease in "l" rats was used to evaluate the effects of three injections of heat-killed Gordonia bronchialis, Rhodococcus coprophilus or saline on Trypanosoma cruzi parasitaemia and acute and chronic myocarditis, sequelae of the infection. Two vaccinating injections were given prior to challenge with T. cruzi, and the third, immunotherapeutic, injection was given 7 days after challenge. Treatment with either actinomycete significantly reduced acute parasitaemia (p<0.04), modified cellular infiltration during acute myocarditis and limited chronic myocarditis (p<0.03) in comparison with the saline-treated control animals. Immunological investigations showed that both bacterial preparations achieved their results through different mechanisms. The relevance of our findings to human Chagas' disease is discussed.
Assuntos
Actinomycetales/imunologia , Doença de Chagas/imunologia , Imunização , Animais , Anticorpos Antiprotozoários/sangue , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Cardiomiopatia Chagásica/imunologia , Microbiologia Ambiental , Imunoglobulina G/sangue , Masculino , Parasitemia/prevenção & controle , Ratos , SuspensõesRESUMO
Peripheral blood mononuclear cells taken from 32 patients with Rheumatoid Arthritis (RA) receiving neither steroids nor methotrexate and 34 healthy controls were examined for lymphoproliferation in the presence of ultrasonic extracts of 14 different mycobacterial species or serotypes, of an extract of Candida albicans and of 2 mitogens. Additionally, cells were incubated for 96 hours alone, or with Mycobacterium tuberculosis (M.tb) sonicate or Concanavalin-A (Con-A), and supernatants were tested for a range of cytokines. Lymphocytes of rheumatoid patients were less reactive than controls to all the mycobacterial preparations, but no different in their responses to mitogens. Stimulation of patients' cells with M.tb sonicate induced significantly less interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) but more transforming growth factor- beta (TGF-beta) than controls. Even stimulation with Con-A induced much less IFN-gamma in patient's cells than in those of controls. The combination of reduced responses to the mycobacterial reagents and reduced stimulation of type 1 cytokines by the sonicate of M.tb, suggests reduced responsiveness to group i, common mycobacterial antigens. Such findings need not indicate involvement of mycobacteria specifically in the disease aetiology, but provide novel information on the immunopathological abnormalities, which may explain the reported increased susceptibility to mycobacteria of RA patients.
Assuntos
Artrite Reumatoide/imunologia , Citocinas/biossíntese , Inflamação/sangue , Interferon gama/biossíntese , Leucócitos/microbiologia , Mycobacteriaceae/imunologia , Adulto , Candida albicans/imunologia , Epitopos , Feminino , Humanos , Técnicas In Vitro , Mononucleose Infecciosa/imunologia , Ativação Linfocitária/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Mitógenos/imunologia , Linfócitos T/imunologiaAssuntos
Antígenos de Bactérias/imunologia , Distribuição por Sexo , Fatores de Risco , Hanseníase/epidemiologia , Hanseníase/etiologia , Hanseníase/prevenção & controle , Incidência , Malaui/epidemiologia , Microbiologia da Água , Microbiologia do Solo , Mycobacterium/classificação , Mycobacterium/crescimento & desenvolvimento , Mycobacterium/imunologia , Mycobacterium/patogenicidade , Pele/imunologia , Saúde da População Rural/estatística & dados numéricos , Teste Tuberculínico , Tuberculose/epidemiologia , Tuberculose/etiologia , Tuberculose/prevenção & controle , Vigilância da PopulaçãoRESUMO
The immune response is impaired in the silent stage of Chagas' disease. We used quadruple skin-testing with new tuberculins in 37 adults who were symptom-free but seropositive for Trypanosoma cruzi and in 37 matched seronegative controls. Whereas 19% of controls responded to common mycobacterial antigens, none of the Chagas' seropositive group responded to them (p < 0.006), demonstrating specificity in their unresponsiveness. The enhanced tuberculin reactivity after BCG vaccination in the control group was suppressed in seropositive subjects (p < 0.002). Selective loss of response to common mycobacterial antigens may have implications for the autoimmune pathology of Chagas' disease, and for susceptibility to tuberculosis, leprosy, and HIV disease.
Assuntos
Doença de Chagas/imunologia , Trypanosoma cruzi/imunologia , Adulto , Animais , Antígenos de Protozoários/sangue , Antígenos de Protozoários/imunologia , Feminino , Humanos , Imunidade Celular , Masculino , Mycobacterium bovis/imunologia , Testes Cutâneos , Teste TuberculínicoAssuntos
Autoanticorpos/biossíntese , Autoimunidade , Citocinas/biossíntese , Doenças Autoimunes/etiologia , Doenças Autoimunes/imunologia , Doenças Autoimunes/microbiologia , Fatores de Tempo , Hanseníase/complicações , Hanseníase/imunologia , Imunidade Celular , Imunoglobulina G/imunologia , Infecções por Mycobacterium/complicações , Infecções por Mycobacterium/imunologia , Modelos Biológicos , Tuberculose/complicações , Tuberculose/imunologiaRESUMO
Después de la administración de la inmunoterapia no deben presentarse reaciones graves y el índice bacterial debe disminuir rápidamente a cero. Las biopsias deben retornar a valores normales. La mejoría neurológica debe ser lo más completa posible. Si todo esto se puede conseguir, la lepra será una enfermedad muy distinta en el siglo XXI.
Assuntos
Hanseníase Virchowiana , ImunoterapiaRESUMO
Skinh test reagents that have been used to investigate the disease process, immunology and epidemiology of leporsy include preparations of leprosy bacilli themselves, of Mycobacterium tuberculosis and of a range of other mycobacterial species.