The Danger Model And Immunity

危险模型和免疫

• 批准号: 6822087
• 负责人: POLLY C MATZINGER
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6822087
• 关键词: T lymphocyte; autoimmunity; biological signal transduction; coagulation factor IX; dendritic cells; genetically modified animals; immune tolerance /unresponsiveness; immunologic memory; laboratory mouse; leukocyte activation /transformation; neoplasm /cancer vaccine; polymerase chain reaction; pregnancy immunology; sheep; transplantation immunology; vaccine development

SUMMARY OF WORK: PURPOSE: Nine years ago, I proposed a new model of the immune system (the Danger model) based on the assumption that the immune system's function is to discriminate between dangerous and harmless things rather than self and non-self. Because this model has tremendous implications for such subjects as cancer, transplantation, neonatal and adult vaccines, parasitology, and autoimmunity, we have been testing its basic premises and its applicability in several areas. RESULTS FROM THE PAST YEAR: 1) NEONATAL IMMUNITY: neonatal mice do not seem to be impaired in their ability to respond to a vaccine, even if they have received passive antibody from their mothers 2) TOLERANCE (in HEMOPHILIA) : A) oral administration of Factor VIII or factor IX induces immunological tolerance and corrects the bleeding time in hemophiliac mice. 3) T CELLS: A) naive and memory T cells do not need MHC molecules for survival or the initiation of homeostatic division, but do seem to need MHC for the transition to CD44-high memory cells B) CD4 helper T cells can reject tumors in the absence of CD8 killers 4) DENDRITIC CELLS: A) dendritic cells can be activated by endogenous hydrophobic substances B) the early IL-4 necessary to generate Th2 responses seems to have its effect on dendritic cells. C) Memory T cells communicate with naive T cells via a dendritic cell, by educating the dendritic cell to pass on the appropriate messages.

工作摘要：目的：九年前，我提出了一种基于免疫系统功能的假设是区分危险和无害事物而不是自我和非自我的假设，提出了一种免疫系统（危险模型）的新模型。由于该模型对癌症，移植，新生儿和成人疫苗，寄生虫学和自身免疫等受试者具有巨大的影响，因此我们一直在测试其基本前提及其在多个领域的适用性。过去一年的结果：1）新生儿免疫：新生儿小鼠似乎对疫苗反应的能力似乎并没有受到损害，即使他们从母亲那里收到了被动抗体2）耐受性（在血友病中）：a）口服VIII或因子IX因子IX因免疫学耐受性和纠正症状而导致的症状。 3）T细胞：a）幼稚和记忆T细胞不需要MHC分子存活或开始稳态分裂，但似乎确实需要MHC来过渡到CD444高的记忆细胞b）CD4 Helper T细胞可以拒绝CD8杀伤细胞的缺乏的CD4 Helper T细胞可以拒绝肿瘤。 TH2反应似乎对树突状细胞有影响。 c）记忆T细胞通过教育树突细胞传递适当的消息，与幼稚的T细胞通过树突细胞与幼稚的T细胞通信。