RESUMO
Patients with antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides (AAV) have an expansion of effector memory Tcells in peripheral blood. The enlarged effector memory cell population contains distinct cell subsets, including Thelper type 1 (Th1) CD4+ Tcells lacking co-stimulatory CD28 expression and Th17 cells in granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) and Th2 type and Th17 cells in eosinophilic granulomatosis with polyangiitis (EGPA). The cytokine response of autoreactive proteinase 3 (PR3)-specific effector memory Tcells is skewed towards an increase of Th2 type, Th17, and Th22 cell fractions in GPA. Anomalous effector memory CD4+ Tcell co-stimulation is suggested by the aberrant expression of Pselectin glycoprotein ligand-1, ß2 integrin, chemokine receptors, natural-killer group 2 member D (NKG2D) and other activating receptors. The increased expression of these receptors is accompanied by Tcell activation and migration to inflamed tissues. Tcells are abundant and secrete proinflammatory cytokines in inflammatory lesions in AAV. The Tcell mediated tissue damage correlates with renal outcome, whereas Bcell infiltration does not. Activation of lesional CD4+NKG2D+ effector memory Tcells is independent of the antigen; moreover, CD4+NKG2D+ effector memory Tcells display NK-cell-like cytotoxicity towards microvascular endothelial cells in vitro. Thus, effector memory Tcells play an important role in tissue damage and disease progression in AAV. Sequentially administered or combined with Bcell depleting therapy, Tcell-directed therapies, especially those directed against effector memory CD4+ Tcells, may further improve the outcome and help to achieve long-term remissions in AAV.
RESUMO
Patients with antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides (AAV) have an expansion of effector memory Tcells in peripheral blood. The enlarged effector memory cell population contains distinct cell subsets, including Thelper type 1 (Th1) CD4+ Tcells lacking co-stimulatory CD28 expression and Th17 cells in granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) and Th2 type and Th17 cells in eosinophilic granulomatosis with polyangiitis (EGPA). The cytokine response of autoreactive proteinase 3 (PR3)-specific effector memory Tcells is skewed towards an increase of Th2 type, Th17 and Th22 cell fractions in GPA. Anomalous effector memory CD4+ Tcell co-stimulation is suggested by the aberrant expression of Pselectin glycoprotein ligand1, beta2 integrin, chemokine receptors, natural-killer group 2 member D (NKG2D) and other activating receptors. The increased expression of these receptors is accompanied by Tcell activation and migration to inflamed tissues. The Tcells are abundant and secrete proinflammatory cytokines in inflammatory lesions in AAV. The Tcell mediated tissue damage correlates with renal outcome, whereas B-cell infiltration does not. Activation of lesional CD4+NKG2D+ effector memory Tcells is independent of the antigen; moreover, CD4+NKG2D+ effector memory Tcells display NK-cell-like cytotoxicity towards microvascular endothelial cells in vitro. Thus, effector memory Tcells play an important role in tissue damage and disease progression in AAV. Sequentially administered or combined with B-cell depleting therapy, Tcell-directed therapies, especially those directed against effector memory CD4+ Tcells, may further improve the outcome and help to achieve long-term remission in AAV.
Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/terapia , Anticorpos Anticitoplasma de Neutrófilos/imunologia , Imunoterapia/métodos , Modelos Imunológicos , Linfócitos T Auxiliares-Indutores/imunologia , Medicina Baseada em Evidências , Alemanha , Humanos , Resultado do TratamentoRESUMO
Inertial-range cascade phenomenology is used to predict Prandtl-number (Pr) dependencies of turbulent flame properties. A unified picture of turbulent flame structure and burning velocity is developed that encompasses all Pr regimes. Implications of the analysis for gaseous flames (Pr near unity), autocatalytic fronts in liquids (high Pr), and astrophysical flames (low Pr) are noted.
RESUMO
A simple, empirically motivated model is proposed to explain the transfer of imposed large scale anisotropy to small scales in high-Reynolds-number turbulence. Observed power-law scalings of anisotropy metrics are interpreted as manifestations of power-law scalings governing high-gradient regions resulting from compressional eddy motions. The model is used to interpret the measured moment-order dependencies of the exponents and amplitudes of odd-order structure functions and derivative moments that vanish in the absence of anisotropy.
Assuntos
Escherichia coli/genética , Vetores Genéticos , Proteínas Recombinantes/genética , Animais , Técnicas Bacteriológicas , Sequência de Bases , Linhagem Celular , Citomegalovirus/genética , Primers do DNA/genética , DNA Complementar/genética , Expressão Gênica , Humanos , Plasmídeos/genética , Reação em Cadeia da Polimerase , Proteínas Recombinantes/biossíntese , Transfecção , Transformação GenéticaRESUMO
A straight filamentary spark produced by a laser has been used to image the spatial distribution of gases in a jet of methane in air. The technique provides a direct map of a conserved scalar quantity useful in modeling turbulent reacting flows and may have other experimental advantages.