Regulation of Local B Cell Responses to Influenza Under Conditions of Infection,

感染条件下局部 B 细胞对流感反应的调节，

• 批准号: 8089286
• 负责人: JAN S. ERIKSON
• 金额: $ 27.17万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2014-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8089286
• 关键词: Affect; B-Lymphocytes; CD4 Positive T Lymphocytes; Cell Survival; Cells; Characteristics; Development; Effector Cell; Elderly; Epithelial Cells; Family member; Goals; Health; Helper-Inducer T-Lymphocyte; Host Defense; Human; Immune; Immune response; Immunity; In Situ; Infection; Inflammatory; Influenza; Influenza vaccination; Institutes; Laboratories; Lead; Longevity; Lung; Lymphoid; Maintenance; Mediating; Memory; Memory B-Lymphocyte; Morbidity - disease rate; Nature; Organ; Pathology; Pennsylvania; Plasma Cells; Play; Production; Reagent; Regulation; Regulatory T-Lymphocyte; Respiratory System; Respiratory tract structure; Role; Streptococcus pneumoniae; Universities; Vaccination; Vaccines; Viral; Virus; Virus Diseases; anti-influenza; chemokine receptor; influenza virus vaccine; influenzavirus; mortality; neutralizing antibody; receptor expression; response; superinfection

Influenza virus poses a major threat to human health. It also predisposes to superinfection of the respiratory tract (RT), most commonly by Streptococcus pneumonia, and is responsible for . significant morbidity and mortality, particularly in the young and elderly. B cells play a vital role in immunity to influenza virus, highlighted by the production of viral-neutralizing antibodies and in the efficacy of influenza vaccines. While it is appreciated that B cells play a critical role in the host response to influenza virus, less is known about the nature of the protective humoral response in the RT. Our project proposes to comprehensively analyze and compare the B cell response in the lung to influenza virus under conditions of viral infection with or without bacterial co-infection as well as vaccination. We hypothesize that the B cell response to influenza virus will have distinct signatures in these divergent contexts. Emphasis will be placed on features of the local RT immunity that promote anti-influenza B cell survival, maturation and differentiation. We will also identify the mechanisms that govern the development, recruitment and maintenance of plasma cells (PC) in the RT. While short-term PC may participate in rapid first line of host defense, long-term PCs and memory cells are critical for the development of lasting protection. By defining the anti-influenza response in situ where the virus infects lung epithelial cells, we may be better equipped to induce targeted mucosal protection through vaccination.

流感病毒对人类健康构成了重大威胁。它也易于超级感染 呼吸道（RT），最常见于肺炎链球菌，并负责 。显着的发病率和死亡率，特别是在年轻人和老年人中。 B细胞在 对流感病毒的免疫力，由病毒中和抗体的产生强调 流感疫苗的功效。虽然不认为B细胞在宿主中起关键作用 对流感病毒的反应，对保护性体液反应的性质知之甚少 RT。我们的项目建议在 在病毒感染条件下，有或没有细菌共感染的病毒感染条件下，肺部为流感病毒 作为疫苗接种。 我们假设B细胞对流感病毒的反应将在 这些不同的背景。重点将放在当地RT免疫的特征上 促进抗激素B细胞存活，成熟和分化。我们还将确定 控制浆细胞（PC）的发展，募集和维护的机制 RT。虽然短期PC可能会参与宿主防御的快速第一线，长期PC和 记忆细胞对于持久保护的发展至关重要。通过定义抗激素 病毒感染肺上皮细胞的原位反应，我们可能会更好地诱导 通过疫苗接种靶向粘膜保护。