IMMUNE RESPONSES TO PERIODONTOPATHOGENS IN SCID MICE

免疫系统的性质和在慢性阻塞性肺疾病发病中的作用 牙周病(PD)目前仍不清楚。几项研究表明， 免疫系统有不良影响，并导致这种疾病。 过程，而另一些人则认为它扮演的主要角色是最小化或 预防疾病。为了更好地确定宿主免疫系统在 对于帕金森病的发病机制，我们建议开发和应用重症 联合免疫缺陷(SCID)小鼠模型研究人类免疫 对牙周病原体的反应。SCID小鼠缺乏功能性免疫 因此，接受异种移植物。在初步研究中， 我们已经证明了用患者细胞重组的SCID小鼠 与局限性青少年牙周炎(SCID-LJP)发展成功能性 免疫系统具有与人类捐赠者相似的免疫系统。 需要检验的基本假设是，免疫系统发挥着 具有预防或延缓牙周感染的保护作用。具体来说， 我们认为诱导一种免疫反应能够中和 可能促进细菌毒力的因素将增强寄主抗药性 为了疾病。本研究分为三个具体目标：(1)发展 并优化了用于人体免疫分析的SCID小鼠模型 对伴生放线杆菌的反应。(2)确定是否 放线菌伴生菌的单个抗原能够增强 SCID-LJP小鼠的保护性免疫。三组抗原将是 使用：潜在毒力因子(白毒素、免疫抑制 因子和成纤维细胞抑制因子)，免疫优势抗原(内毒素) 外膜蛋白。(3)进一步明确东道主对 并鉴定LTX和LTX的亚区、成分和/或表位 负责增强SCID-LJP保护性免疫的基因 老鼠。 总而言之，这些研究将进一步加深我们对 通过帮助确定帕金森病的性质、特异性和 人类免疫反应对伴生放线菌的适应性。 此外，这项调查可能会为未来提供一个基础 发展延缓和预防牙周病的疫苗。

The nature and contribution of the immune system to the pathogenesis of periodontal disease (PD) remains unclear. Several studies suggest that the immune system has undesirable effects and contributes to the disease process while others propose that it plays a primary role to minimize or prevent disease. To better define the role of the host's immune system in the pathogenesis of PD, we propose to develop and apply the severe combined immunodeficient (SCID) mouse model to study human immune responses to periodontal pathogens. SCID mice lack a functional immune system and, therefore, accept xenogeneic grafts. In preliminary studies, we have demonstrated that SCID mice reconstituted with cells from patients with localized juvenile periodontitis (SCID-LJP) develop a functional immune system with a repertoire similar to that of the human donor. The fundamental hypothesis to be tested is that the immune system plays a protective role to prevent or retard periodontal infection. Specifically, we propose that induction of an immune response capable of neutralizing factors that may promote bacterial virulence will enhance host resistance to disease. The study is divided into three specific aims: (1) To develop and optimize the SCID mouse model for the analysis of the human immune response to Actinobacillus actinomycetemcomitans. (2) To determine if individual A. actinomycetemcomitans antigens are capable of augmenting protective immunity in SCID-LJP mice. Three groups of antigens will be employed: potential virulence factors (leukotoxin, immunosuppressive factor and fibroblast inhibitory factor), the immunodominant antigen (LPS) and outer membrane proteins. (3) To further define the host response to LTX and identify subregions, components and/or epitopes of LTX and LPS that are responsible for augmentation of protective immunity in SCID-LJP mice. Collectively, these studies will further our understanding of the role of the immune response in PD by helping to define the nature, specificity and adaptability of the human immune response to A. actinomycetemcomitans. Furthermore, this investigation may provide a foundation for the future development of vaccines to retard and prevent periodontal disease.