Mechanisms of Immune Modulation and Periodontal Disease

免疫调节与牙周病的机制

• 批准号: 7422575
• 负责人: Jannet Katz
• 金额: $ 36.38万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7422575
• 关键词: Affect; Antibodies; Antigen-Presenting Cells; Antigens; Bacterial Adhesins; CD80 gene; Cell physiology; Cells; Cholesterol; Condition; Cytokine Activation; Dendritic Cells; Development; Disease; Disruption; Effector Cell; Event; Exposure to; Family; Future; Goals; Hemagglutinin; Histocompatibility Antigens Class II; Immune; Immune response; Immune system; Immunity; Immunization; Infection; Infection prevention; Inflammation; Investigation; Lead; Ligands; Link; Mediating; Membrane Microdomains; Molecular; Pathogenesis; Pathologic; Pattern; Pattern recognition receptor; Periodontal Diseases; Plasma Membrane Lipid Bilayer; Play; Porphyromonas; Porphyromonas gingivalis; Process; Production; Property; Regulation; Role; Signal Pathway; Signal Transduction; Signal Transduction Pathway; Signaling Molecule; Specificity; T-Cell Activation; T-Lymphocyte; Testing; Toll-like receptors; Transcriptional Activation; Up-Regulation; Virulence; Virulence Factors; base; cytokine; immunoregulation; innovation; insight; macrophage; microorganism; microorganism antigen; novel; pathogen; receptor; research study; response; therapeutic vaccine; therapy development; vaccine development

The innate and adaptive immune systems are irrevocably linked and both play primary roles in the induction and/or prevention of infections, including periodontal disease. Critical to the initiation of innate and adaptive immune responses to microbial antigens is the participation of Toll-like receptors (TLRs), a family of patternrecognition receptors (PRRs) that detect conserved molecular products of microorganisms. We propose that the immune regulation exerted by the innate immune system upon its interaction with virulence antigens is the basis for the development of therapies geared to manipulate the effector immune response to the advantage and protection of the host. The fundamental hypothesis of our studies is that each microbial antigen is unique in its initial interaction with the host, thus resulting in differences in receptor recognition, activation of signaling pathways and cellular responses. In this regard, we have shown differences in the adaptive immune responses to the hemagglutinin/adhesin virulence antigens Kgp-HArep and HagB derived from Porphyromonas ginigivalis, which suggest that their interactions with the innate immune system differ. We plan to focus our investigations on the TLRs and on dendritic cells since these antigen-presenting cells have the exquisite property of activating naive T cells and thus are critically involved in innate and adaptive responses. In addition, our investigations will pursue an understanding of the ensuing adaptive immune response. Therefore, the aims of this proposal are (1) to determine the role of TLRs in the innate and adaptive response to Kgp-HArep and HagB stimulation; (2) to determine if innate and effector cell responses to Kgp-HArep and HagB require lipid rafts and how the induction of a specific effector response or the use of a certain TLR affects the particular recruitment and concentration of signaling molecules into lipid rafts; and (3) to determine the role of CD25+CD4+ Treg cells in immune responses to Kgp-HArep and HagB and in P. gingivalis infection. It is anticipated that these studies will lead to an understanding of the cellular events that occur when host cells encounter the virulence antigens HArep and HagB, and will provide 1) insight into their role in pathogenesis/immunity and 2) relevant information for the development of vaccines or therapies that will specifically protect or ameliorate infections by the pathogen Porphyromonas gingivalis.

先天性免疫系统和适应性免疫系统是紧密联系在一起的，两者都在诱导中起主要作用。 和/或预防感染，包括牙周病。对先天和适应性的启动至关重要 对微生物抗原的免疫应答是Toll样受体（TLR）的参与，TLR是模式识别家族， 受体（PRR）检测微生物的保守分子产物。我们建议 先天免疫系统在与毒力抗原相互作用时所施加的免疫调节是 开发适合于操纵针对免疫缺陷病毒的效应免疫应答的疗法的基础是： 保护和保护主人。我们研究的基本假设是， 抗原在其与宿主的初始相互作用中是独特的，因此导致受体识别的差异， 激活信号通路和细胞反应。在这方面，我们已经显示出差异， 对血凝素/粘附素毒力抗原Kgp-HArep和HagB衍生的适应性免疫应答 这表明它们与先天免疫系统的相互作用不同。 我们计划将我们的研究重点放在TLR和树突状细胞上，因为这些抗原呈递细胞 具有激活幼稚T细胞的精致特性，因此在先天性和适应性免疫中起关键作用。 应答此外，我们的研究将追求对随后的适应性免疫的理解。 反应因此，本建议的目的是（1）确定TLR在先天性和先天性免疫缺陷中的作用， 对Kgp-HArep和HagB刺激的适应性反应;（2）确定先天和效应细胞反应是否 对Kgp-HArep和HagB的作用需要脂筏，以及如何诱导特异性效应子应答或使用 某些TLR影响信号分子进入脂筏的特定募集和浓度;和 (3)确定CD 25 + CD 4 + Treg细胞在对Kgp-HArep和HagB的免疫应答中以及在P. 牙龈感染 预计这些研究将有助于了解宿主在体内发生的细胞事件 细胞遇到毒力抗原HArep和HagB，并将提供1）深入了解它们在 发病机制/免疫力和2）用于开发疫苗或疗法的相关信息， 特异性地保护或减轻病原体牙龈卟啉单胞菌的感染。