RESUMO
Paracoccidioidomycosis patients show hyperactive humoral immune responses. Consequently, we investigated whether cytokines in supernatants from Paracoccidioides brasiliensis-stimulated gamma/delta T cells support B-cell activation. We detected proliferation of B cells and increased immunoglobulin M (IgM) and IgG production. Thus, gamma/delta T cells may participate in polyclonal B-cell activation during paracoccidioidomycosis.
Assuntos
Linfócitos B/imunologia , Paracoccidioides/imunologia , Subpopulações de Linfócitos T/imunologia , Anticorpos Antifúngicos/biossíntese , Formação de Anticorpos , Antígenos de Fungos/imunologia , Humanos , Ativação Linfocitária , Receptores de Antígenos de Linfócitos T gama-delta/imunologiaRESUMO
Paracoccidioides brasiliensis causes a chronic granulomatous mycosis, prevalent in South America, and cell-mediated immunity represents the principal mode of protection against this fungal infection. We investigated the response of naive cord blood T cells to P. brasiliensis lysates. Our results show: (1) P. brasiliensis stimulates T-cell expansion, interleukin-2 (IL-2) production and differentiation into cytotoxic T cells; (2) T-cell stimulation depends on P. brasiliensis processing and major histocompatibility complex (MHC) class II expression; (3) the responsive T-cell population expresses alpha beta T-cell receptors (TCR) with different V beta gene products, CD4 and CD45RO; (4) the P. brasiliensis components involved in T-cell expansion primarily reside in a high molecular weight (100,000 MW) and a low molecular weight (< 1000 MW) protein fraction. These results indicate that protein antigens of P. brasiliensis stimulate cord blood CD4 alpha beta T cells, independent from in vivo presensitization, and thus question direct correlation of positive in vitro responses with protective immunity in vivo.
Assuntos
Antígenos de Fungos/imunologia , Linfócitos T CD4-Positivos/imunologia , Sangue Fetal/imunologia , Paracoccidioides/imunologia , Receptores de Antígenos de Linfócitos T alfa-beta/imunologia , Células Cultivadas , Antígenos HLA-DR/imunologia , Humanos , Interleucina-2/biossíntese , Ativação Linfocitária , Fenótipo , Linfócitos T Citotóxicos/imunologiaRESUMO
Paracoccidioides brasiliensis, a dimorphic fungus, causes chronic granulomatous mycosis in susceptible individuals. Different reports have shown that cell-mediated immunity is essential for protection against systemic mycosis, including paracoccidioidomycosis. We analyzed the reactivity of alpha beta and gamma delta T cells from unexposed Caucasian donors to P. brasiliensis yeast form components. Our results indicate: (i) alpha beta and gamma delta T cells proliferate after in vitro stimulation with lysates of P. brasiliensis; (ii) similar numbers of alpha beta T cells (f = 1/21,000) and of gamma delta T cells (f = 1/8000) respond to P. brasiliensis; (iii) P. brasiliensis-reactive gamma delta T cells express the V gamma 9V delta 2 TCR; (iv) the stimulatory activity of P. brasiliensis for both alpha beta and gamma delta T cells primarily resides in a high molecular weight (100 kDa) and in a low molecular weight (< 1 kDa) fraction; (v) the ligands responsible for stimulation of both alpha beta and gamma delta T cells are sensitive to proteinase treatment. We conclude that both alpha beta and gamma delta T cells from healthy individuals respond to ubiquitous protein antigens of P. brasiliensis.
Assuntos
Antígenos de Fungos/imunologia , Paracoccidioides/imunologia , Receptores de Antígenos de Linfócitos T alfa-beta/imunologia , Receptores de Antígenos de Linfócitos T gama-delta/imunologia , Subpopulações de Linfócitos T/imunologia , Apresentação de Antígeno/imunologia , Endopeptidase K , Citometria de Fluxo , Humanos , Interleucina-2/biossíntese , Ativação Linfocitária , Serina EndopeptidasesRESUMO
Plasma samples of 14 patients with paracoccidioidomycosis were analysed for components that represent activation of the complement system. Most patients (12/13) showed significant titres of complement-fixing antibodies and 14/14 had increased C4d/C4 ratios. There was no conclusive correlation between these two immunological indices, however. Factor B values of patients were similar to normal donors and fragment Ba was not detected in any of the patients. These results indicate a classical complement pathway activation in the plasma of patients with paracoccidioidomycosis.
Assuntos
Ativação do Complemento/imunologia , Paracoccidioidomicose/imunologia , Adolescente , Adulto , Anticorpos Antifúngicos/sangue , Criança , Complemento C4/análise , Fator B do Complemento/análise , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paracoccidioides/imunologiaRESUMO
The yeast form of Paracoccidioides brasiliensis strain Pb18 was able to activate C3 of normal human serum diluted in phosphate-buffered saline or EGTA-MgCl2 in vitro. C3 convertase was also permissive when Pb18 cells were pre-treated with a pool of immune serum from patients with paracoccidioidomycosis and incubated in serum diluted in EDTA-CaCl2. The components C3, and fragments C3c, C3d, C3g, factor H, factor B, C4 and C5b-9 were demonstrated on the Pb18 cell surface by immunofluorescence although no effect was seen on fungal viability.
Assuntos
Ativação do Complemento/imunologia , Paracoccidioides/imunologia , Complemento C3/imunologia , Humanos , Paracoccidioidomicose/imunologiaRESUMO
Immunity to intracellular bacteria including Mycobacterium tuberculosis, Mycobacterium leprae, and Listeria monocytogenes depends on specific T cells. Evidence to be described suggests that CD4 alpha/beta T cells, CD8 alpha/beta T cells and gamma/delta T cells which interact with each other and with macrophages contribute to acquired resistance against as well as pathogenesis of intracellular bacterial infections.
Assuntos
Bactérias/imunologia , Infecções Bacterianas/imunologia , Células/microbiologia , Macrófagos/imunologia , Subpopulações de Linfócitos T/imunologia , Animais , Infecções Bacterianas/microbiologia , Infecções Bacterianas/patologia , Humanos , Legionella pneumophila/imunologia , Listeria monocytogenes/imunologia , Camundongos , Mycobacterium/imunologia , Receptores de Antígenos de Linfócitos T gama-delta/imunologia , Tuberculose/epidemiologia , Tuberculose/imunologia , Tuberculose/microbiologiaRESUMO
The immunopathology of Chagas' disease was studied in the experimental model of chronic infection in C57BL/10JT or mice. Sublethal infection with Trypanosoma cruzi, Y strain, induced specific antibodies and a delayed hypersensitivity response to parasite antigens. Mice developed chronic chagasic myocarditis but not skeletal muscle myositis. Binding of T cells to infected heart tissue was investigated during short-term cocultivation of lymphocytes with heart cryostat sections. T cells from infected mice and from normal controls bound equally to myocardium and liver sections from both infected and normal mice. A search in depth was attempted with cells heavily tagged with 99mTc. Labeled T cells from chagasic mice bound to both normal and infected myocardium slices. 99mTc-labeled T cells from controls gave the same binding values. Glass-adherent spleen cells behaved identically to T cells. Prior treatment of the tissue with serum from chronically infected mice did not increase the number of binding cells. Peritoneal macrophages tagged with 99mTc-sulfur colloid also bound to infected myocardium slices. The binding of macrophages was not changed by pretreatment of infected tissue with anti-T, cruzi antibodies. In short, this work did not detect any population of T cells or macrophages which could bind specifically to infected heart tissue to initiate an autoreactive process.