Regulation of immune response to influenza by innate immunity.

通过先天免疫调节对流感的免疫反应。

• 批准号: 7275926
• 负责人: Michael Craig Carroll
• 金额: $ 45.98万
• 依托单位: IMMUNE DISEASE INSTITUTE, INC.
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-15 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7275926
• 关键词: Animal Model; Antibodies; Antigenic Variation; B-Lymphocytes; Bioterrorism; CD4 Positive T Lymphocytes; Capsid Proteins; Cells; Complement; Core Protein; Cytotoxic T-Lymphocytes; Development; Effector Cell; Generations; Goals; Health; Helper-Inducer T-Lymphocyte; Hemagglutinin; Human; Immune response; Immune system; Immunoglobulin M; In Vitro; Inflammation; Influenza; Lung; Mammals; Memory; Memory B-Lymphocyte; Molecular; Natural Immunity; Neuraminidase; Nucleocapsid; Regulation; Role; System; T-Lymphocyte; Thinking; Vaccination; Virus Diseases; flu; in vivo; influenzavirus; lymph nodes; neutralizing antibody; response; trafficking

DESCRIPTION (provided by applicant): Influenza virus represents a major worldwide health problem as well as a potential agent for use in bioterrorism. Of the 3 known strains, influenza A is probably the best studied as it infects not only humans but other mammals and can be adapted to animal models. The major antigenic targets-hemagglutinin and neuraminidase- undergo structural changes such that antibodies formed against one strain generally are not protective with a related strain. Because of this "antigenic variation", neutralizing antibodies are not long lasting and necessitate annual vaccination. A cytotoxic T cell response to inner core proteins such as the nucleocapsid that are more conserved; or a antibody that targets conserved regions of the outer coat proteins would be desirable targets for generation of long lasting memory responses. The overall goal of this project is to investigate the cellular and molecular mechanisms underlying the role for innate immunity (complement system and natural IgM) in development of influenza-specific effector and memory T and B cells. Three specific aims are proposed: (i) Examine the role of complement C3 in the activation and expansion of influenza-specific effector and memory CDS T cells. (ii) Examine the role of complement C3 in the development of memory B cells, (iii) Examine the role of natural IgM in host innate and adaptive response to influenza.

描述（由申请人提供）：流感病毒是一个主要的全球性健康问题，也是一种用于生物恐怖主义的潜在制剂。在已知的3种毒株中，甲型流感可能是研究得最好的，因为它不仅感染人类，还感染其他哺乳动物，并且可以适应动物模型。主要的抗原靶点-血凝素和神经氨酸酶-经历结构变化，使得针对一种菌株形成的抗体通常不具有相关菌株的保护性。由于这种“抗原变异”，中和抗体不持久，需要每年接种疫苗。细胞毒性T细胞对更保守的内核蛋白（例如核衣壳）的反应;或者针对外壳蛋白保守区域的抗体将是产生持久记忆反应的理想靶点。本项目的总体目标是研究先天免疫（补体系统和天然IgM）在流感特异性效应和记忆T和B细胞发育中的作用的细胞和分子机制。提出了三个具体目标：（i）检查补体C3在流感特异性效应和记忆CDS T细胞的活化和扩增中的作用。(ii)检查补体C3在记忆B细胞发育中的作用。（iii）检查天然IgM在宿主对流感的先天性和适应性应答中的作用。