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1.
SQUMJ-Sultan Qaboos University Medical Journal. 2014; 14 (1): 65-71
em Inglês | IMEMR | ID: emr-138699

RESUMO

Aflatoxin B[1] [AFB[1]] is a naturally occurring carcinogenic and immunosuppressive compound. This study was designed to measure its toxic effects on human peripheral blood mononuclear cells [PBMC]. The study recruited 7 healthy volunteers. PBMC were isolated and cellular respiration was monitored using a phosphorescence oxygen analyser. The intracellular caspase activity was measured by the caspase-3 substrate N-acetyl-asp-glu-val-asp-7-amino-4-methylcoumarin. Phosphatidylserine exposure and membrane permeability to propidium iodide [PI] were measured by flow cytometry. Cellular oxygen consumption was inhibited by 2.5 micro M and 25 micro M of AFB[1]. Intracellular caspase activity was noted after two hours of incubation with 100 micro M of AFB[1]. The number of Annexin V-positive cells increased as a function of AFB[1] concentration and incubation time. At 50 micro M, a significant number of cells became necrotic after 24 hours [Annexin V-positive and PI-positive]. The results show AFB[1] is toxic to human lymphocytes and that its cytotoxicity is mediated by apoptosis and necrosis

2.
EMJ-Emirates Medical Journal. 2006; 24 (1): 47-56
em Inglês | IMEMR | ID: emr-163221

RESUMO

The role of the macrophage vis-a-vis NK/T cells in determining the outcome of an immune response to a pathogen, whether Th-1 or Th-2, constitutes a fundamental issue in immunoregulation. Such knowledge is also of paramount importance in understanding the immunopathology of chronic human diseases like tuberculosis, leishmaniasis, hepatosplenic schistosomiasis, cysticercosis and neurocysticercosis. The conventional hypothesis states that interferon gamma [IFN-gamma] produced by T-cells and NK cells, in response to interleukin-12 [IL-12] from macrophages directs the immune response towards a Th-1 type, while IL-4, IL-5 and IL-10 result in a Th-2 type, upon antigen presentation with the necessary co-stimulatory molecules. In this report, we provide evidence that parasite glycans induce IFN-gamma and interleukin-6 [IL-6] production in na‹ve murine spleen cells, via toll like receptor [TLR] activation, possibly from macrophages. The IFN-gamma response is self-limiting. We propose that the relative balance of IFN-gamma and IL-6 determines the total immune response, whether Th-1, Th-1/Th-2 or Th-2 biased. Prolonged stimulation of macrophages by parasite glycans via TLRs down regulates the macrophage IFN-gamma response resulting an IL-6 dominated Th-2 environment. This is an adaptation by the parasite to down regulate the early parasite restrictive Th-1 response to a late parasite permissive Th-2 response during the course of infection. It is proposed that in parasitic helminth infections, the generation of either a Th-1 or a Th-2 response is determined at least in part at the macrophage level, prior to the involvement of NK/T cells and occurs when macrophages first encounter pathogen specific molecules via TLRs

3.
EMJ-Emirates Medical Journal. 2006; 24 (1): 47-56
em Inglês | IMEMR | ID: emr-76573

RESUMO

The role of the macrophage vis-a-vis NK/T cells in determining the outcome of an immune response to a pathogen, whether Th-1 or Th-2, constitutes a fundamental issue in immunoregulation. Such knowledge is also of paramount importance in understanding the immunopathology of chronic human diseases like tuberculosis, leishmaniasis, hepatosplenic schistosomiasis, cysticercosis and neurocysticercosis. The conventional hypothesis states that interferon gamma [IFN-gamma] produced by T cells and NK cells, in response to interleukin-12 [IL-12,] from macrophages directs the immune response towards a Th-1 type, while IL-4, IL-5 and IL-10 result in a Th-2 type, upon antigen presentation with the necessary co-stimulatory molecules. In this report, we provide evidence that parasite glycans induce IFN-gamma and interleukin-6 [IL-6] production in na‹ve murine spleen cells, via toll like receptor [TLR] activation, possibly from macrophages. The JFN-gamma response is self limiting. We propose that the relative balance of IFN-gamma and IL-6 determines the total immune response, whether Th-1, Th-1/Th-2 or Th-2 biased. Prolonged stimulation of macrophages by parasite glycans via TLRs down regulates the macrophage IFN-gamma response resulting an IL-6 dominated Th-2 environment. This is an adaptation by the parasite to down regulate the early parasite restrictive Th-1 response to a late parasite permissive Th-2 response during the course of infection. It is proposed that in parasitic helminth infections, the generation of either a Th-1 or a Th-2 response is determined at least in part at the macrophage level, prior to the involvement of NK/T cells and occurs when macrophages first encounter pathogen specific molecules via TLRs


Assuntos
Polissacarídeos , Imunidade , Receptores Toll-Like , Interferon gama , Células Th1 , Células Th2 , Interleucina-6
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