Conference--Host Resistance/Susceptability/Immunopatholo

会议--宿主耐药性/敏感性/免疫病理学

• 批准号: 7002157
• 负责人: Anne O''Garra
• 金额: $ 1.1万
• 依托单位: KEYSTONE SYMPOSIA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-06-01 至 2006-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7002157
• 关键词: bacterial cytopathogenic effect; bacterial disease; host organism interaction; immune response; immunity; immunopathology; meeting /conference /symposium; travel; virus cytopathogenic effect; virus diseases

The type of immune response that is elicited upon infection of a host with a pathogen is critical in determining whether the pathogen is eradicated or whether chronic infection ensues. The inability thus far to intervene immunologically to abrogate many chronic diseases such as HIV, malaria, TB, schistosomiasis for example, highlights the need for a deeper understanding of the immune response to infectious challenge. Successful protective effector responses to intracellular pathogens such as parasites, bacteria and viruses are initiated by cells of the innate immune response which produce effector cytokines such as TNF, IL-12 or IFN-alpha which stimulate antigen-specific Th1 cells producing IFN-gamma, and CD8+ T cytotoxic T cell (CTL). Humoral immune responses also offer protection against pathogens, however rapid mutations in the organisms and/or the lack of immunizing regimens which lead to long-term protection, impede successful vaccination. Host mutations in cytokine signalling pathways and signalling pathways downstream of pattern recognition receptors on host immune cells, result in profound susceptibility to a number of pathogens. Furthermore, many organisms such as Leishmania, Schistosoma or Mycobacteria inhibit protective immune responses via the induction of suppressive cytokines, whereas influenza has developed molecular mechanisms to interfere directly with signalling pathways important for the induction of the host antiviral response. Major reasons why we have failed to-date in eliminating human pathogens are: successful strategies of immunoevasion developed by pathogens to dampen an immune response, and conversely pathogen induced immunopathologies complicate infections. Furthermore, the emergence and reemergence of many infectious pathogens throughout human history, the difficulty in producing effective vaccines to protect against numerous pathogens, and the inability to intervene immunologically to abrogate many chronic infectious diseases such as HIV, malaria, TB, and schistosomiasis for example, highlights the need for a deeper understanding of the immune response to infectious challenge. The proposed Keystone Meeting will result in cross-fertilization of knowledge gained from animal models of infectious disease to human immune responses to such important pathogens and is critical to advance the treatment and prevention of devastating pathogens.

宿主感染病原体后引发的免疫反应类型对于免疫反应至关重要 确定病原体是否被根除或是否发生慢性感染。迄今为止，还无法通过免疫学干预来消除许多慢性疾病，例如艾滋病毒、疟疾、结核病、血吸虫病，这突出表明需要更深入地了解针对感染挑战的免疫反应。对细胞内病原体（如寄生虫、细菌和病毒）成功的保护性效应反应是由先天免疫反应的细胞启动的，这些细胞产生效应细胞因子，如 TNF、IL-12 或 IFN-α，刺激抗原特异性 Th1 细胞产生 IFN-γ，和 CD8+ T 细胞毒性 T 细胞 (CTL)。体液免疫反应还可以提供针对病原体的保护，但是生物体的快速突变和/或缺乏导致长期保护的免疫方案会阻碍疫苗接种的成功。宿主免疫细胞上细胞因子信号通路和模式识别受体下游信号通路的宿主突变，导致对多种病原体的高度易感性。此外，许多生物体，如利什曼原虫、血吸虫或分枝杆菌，通过诱导抑制性细胞因子来抑制保护性免疫反应，而流感已经发展出分子机制，可以直接干扰对于诱导宿主抗病毒反应很重要的信号通路。迄今为止，我们未能消灭人类病原体的主要原因是：病原体开发出成功的免疫逃避策略来抑制免疫反应，反之亦然。 病原体诱导的免疫病理使感染复杂化。此外，人类历史上许多传染性病原体的出现和重新出现，生产有效疫苗来预防多种病原体的困难，以及无法通过免疫干预来消除许多慢性传染病，例如艾滋病毒、疟疾、结核病和血吸虫病，强调需要更深入地了解对感染挑战的免疫反应。拟议的基石会议将使从传染病动物模型获得的知识与人类对此类重要病原体的免疫反应相结合，对于推进毁灭性病原体的治疗和预防至关重要。