Project 3 - A Role for Plasma Cells as Antigen Presenting Cells During Malaria

项目 3 - 浆细胞在疟疾期间作为抗原呈递细胞的作用

• 批准号: 8841765
• 负责人: Jason S Stumhofer
• 金额: $ 29.5万
• 依托单位: UNIV OF ARKANSAS FOR MED SCIS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至 2016-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8841765
• 关键词: Acute; Adult; Affect; Antibodies; Antibody Formation; Antibody Response; Antigen Presentation; Antigen Presentation Pathway; Antigen-Presenting Cells; Antigens; Area; B-Lymphocytes; Biology; Blood; Bone Marrow; CD4 Positive T Lymphocytes; Carrier Proteins; Cells; Cessation of life; Child; Chimera organism; Communicable Diseases; Complex; Conflict (Psychology); Contracts; Dendritic Cells; Development; Disease; Exposure to; Generations; Goals; Haptens; Helper-Inducer T-Lymphocyte; Histocompatibility Antigens Class II; Human; Humoral Immunities; Immune response; Immunity; Immunization; Immunoglobulin Class Switching; Immunoglobulin G; Immunologic Memory; Inbred Strains Mice; Infection; Inflammatory Response; Kinetics; Lead; Life; Lymphoid; Maintenance; Malaria; Malaria Vaccines; Mediating; Memory; Memory B-Lymphocyte; Mus; Organ; Outcome; Parasite Control; Parasites; Pathogenesis; Pathway interactions; Peptides; Plasma Cells; Plasmodium; Positioning Attribute; Process; Public Health; Reaction; Regulation; Role; Specificity; Spleen; Staging; Structure of germinal center of lymph node; Surface; T cell response; T-Lymphocyte; T-Lymphocyte Subsets; Vaccines; cell type; combat; design; experience; improved; in vivo; insight; long term memory; microbial; migration; neutralizing antibody; novel; pathogen; research study; response; secondary infection; vaccine candidate; vaccine development

The protozoan parasite Plasmodium is the causitive agent of malaria, which remains one of the most prominent public health challenges in the world today. The overall goal of this project is to examine the function of plasma cells as antigen presenting cells (APCs) during a primary and secondary immune response against Plasmodium. We hypothesize that isotype-switched plasma cells will be able to present antigen throughout the primary and secondary immune response against Plasmodium and that these cells will serve to regulate the germinal center response in the spleen, particularly following a secondary infection. We have proposed studies (Aims 1) to investigate the ability of plasma cells to express the machinery necessary for antigen presentation following infection with P. yoelii and to determine the capacity of this cell type to activate a CD4[+] T-cell response, with a specific focus on determining how antigen presentation by plasma cells influences the activity of follicular helper T cells, a specialized subset of T cells involved in antibody production. We will also examine the localization of IgG[+] plasma cells and memory B cells in the spleen to determine how their positioning in the spleen influences the kinetics of a secondary response (Aims 2). A role for plasma cells in the presentation of antigen during Plasmodium infection has not been considered previously, and identifying this cell as a functional APC as well as determining how this cell type regulates a secondary antibody-mediated immune response will further our understanding of how long-term immunity is generated against this pathogen, information that will be pertinant for successful vaccine development.

原生动物寄生虫疟原虫是疟疾的病原体，疟疾仍然是当今世界最突出的公共卫生挑战之一。该项目的总体目标是检查浆细胞在针对疟原虫的初次和二次免疫反应期间作为抗原呈递细胞 (APC) 的功能。我们假设同种型转换的浆细胞将能够在针对疟原虫的初次和二次免疫反应中呈递抗原，并且这些细胞将用于调节脾脏中的生发中心反应，特别是在继发感染后。我们提出了研究（目标 1）来调查约氏疟原虫感染后浆细胞表达抗原呈递所需机制的能力，并确定这种细胞类型激活 CD4[+] T 细胞反应的能力，特别关注确定浆细胞的抗原呈递如何影响滤泡辅助 T 细胞的活性，滤泡辅助 T 细胞是参与抗体产生的特殊 T 细胞亚群。我们还将检查 IgG[+] 浆细胞和记忆 B 细胞在脾脏中的定位，以确定它们在脾脏中的定位如何影响次级反应的动力学（目标 2）。以前没有考虑过浆细胞在疟原虫感染期间呈递抗原中的作用，将这种细胞识别为功能性 APC 以及确定这种细胞类型如何调节二抗介导的免疫反应将进一步了解我们需要多长时间- 针对这种病原体产生长期免疫力，这些信息将与疫苗的成功开发相关。