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Escape of pathogens from the host immune response by mutations and mimicry. Possible means to improve vaccine performance

机译:通过突变和模仿从宿主免疫应答中逃脱病原体。改善疫苗性能的可能方法

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The ability of certain pathogens, such as human immunodeficiency, hepatitis C, herpes simplex, influenza viruses, Plasmodium falciparum, etc., to escape from host immune response is generally ascribed to high mutation rate of their genome. We challenge this assumption and propose that molecular mimicry of host antigens by these pathogens could also participate to this resistance. Several studies show that there is no correlation between the mutation rate value of a pathogen and the possibility to develop an effective vaccine. On the other hand, pathogens which do not respond to vaccine are usually reported to display host protein mimicry. We propose to suppress in the thymus the epitopes of the self which are in common with the pathogen. This could be achieved by intrathymic injection of antibodies against this microorganism. These antibodies would be obtained by vaccination of a foreign animal species. It is expected that the negative selection of the CD4(+) and CD8(+) T lymphocytes specific for these epitopes would be prevented, that the number of epitopes recognized as foreign to the host would be increased and that the immune response diversity would be enhanced. (C) 2015 Elsevier Ltd. All rights reserved.
机译:某些病原体,例如人类免疫缺陷,丙型肝炎,单纯疱疹,流感病毒,恶性疟原虫等,逃脱宿主免疫反应的能力通常归因于其基因组的高突变率。我们挑战这一假设,并提出这些病原体对宿主抗原的分子模拟也可以参与这种抗性。几项研究表明,病原体的突变率值与开发有效疫苗的可能性之间没有关联。另一方面,通常不对疫苗反应的病原体显示出宿主蛋白的拟态。我们建议抑制胸腺中与病原体共有的自身抗原决定簇。这可以通过胸腺内注射针对该微生物的抗体来实现。这些抗体可通过接种外来动物物种获得。预期将阻止对这些表位特异的CD4(+)和CD8(+)T淋巴细胞的阴性选择,被识别为宿主异源的表位数量将增加,并且免疫应答多样性将增加。增强。 (C)2015 Elsevier Ltd.保留所有权利。

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