Mechanisms of Immune Modulation and Peridontal Disease
免疫调节与牙周疾病的机制
基本信息
- 批准号:6361859
- 负责人:
- 金额:$ 29.06万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2001
- 资助国家:美国
- 起止时间:2001-09-01 至 2006-06-30
- 项目状态:已结题
- 来源:
- 关键词:B cell lymphoma Bacteroides gingivalis CD40 molecule SDS polyacrylamide gel electrophoresis bacteria infection mechanism bacterial antigens bacterial genetics cellular immunity cholera toxin cytokine enzyme linked immunosorbent assay flow cytometry gene expression immunization immunogenetics immunoglobulin G immunomodulators immunoregulation laboratory mouse monoclonal antibody mucosal immunity pathologic process periodontium disorder phospholipids surface antigens western blottings
项目摘要
Periodontal disease is the result of the host response to
periodontal pathogens such as Porphyromonas gingivalis. P. gingivalis is a
black-pigmented, Gram-negative pathogen, which expresses various virulence
factors implicated in disease. The overall goal of this project is to define
the cellular mechanism(s) involved in the induction of host responses
protective against P. gingivalis infection. The studies proposed will
concentrate on delineating the mechanisms by which adjuvants modulate host
responses to P. gingivalis antigens. Emphasis will be placed on the role of B7
co-stimulatory molecules in host responses and in infection by P. gingivalis,
and on the involvement of cytokines, specific target cells, and other cell
surface receptors. Specifically, there are plans to: 1) Determine the
immunogenicity of the recombinant catalytic domain of the lysine-specific
protease Kgp (rKgp-CAT) and the HagA repeat domain (rHArep) of P. gingivalis,
and the effect of the B subunit of cholera toxin (CTB) and monophosphoryl lipid
A (MPL) in modulating responses to these antigens following intranasal
immunization, The level, isotype and IgG subclass of antibodies induced to
HArep or Kgp-CAT in serum and external secretion$ will be measured by ELISA.
The effects of CTB and MPL in enhancing/shifting responses will be further
characterized by measuring antigen-specific proliferation and cytokine
production. The effect of the responses, especially the nature of the
antibodies, on protection will also be determined. 2) Determine the mechanisms
by which the adjuvants CTB and MPL modulate the induction of the immune
response. These studies will determine the involvement of the co-stimulatory B7
molecules in the immunoenhancing ability of the adjuvants and in P. gingivalis
infection, the target cells affected by the adjuvants and the association
between MPL, the Toll-like receptors and B7 co-stimulatory molecules. Groups of
mice deficient in B7-l (B7-1-/-), B7-2 (B7-2j or both (B7-1/B7-2-/-) molecules
and normal controls will be immunized with HArep or Kgp-CAT with and without
CTB or MIPL. The levels of antibody and antibody-secreting cells will be
assessed by ELISA and ELISPOT method. The effect of adjuvants on the expression
of B7 molecules and of CD4OL will be analyzed by FACS. Differential regulation
of cytokines induced and proliferative responses will also be assessed. The
involvement of B7 co-stimulation in P. gingivalis infection will be assessed in
B7 deficient mice. These studies will provide information on the mechanisms by
which mucosal adjuvants modulate host immune responses, the target cells
through which their adjuvanticity is exerted and the involvement of
co-stimulatory signals provided by B7 molecules and of Toll-like receptors. An
understanding of these processes is crucial for the development of means to
interrupt/prevent periodontal disease pathogenesis by Porphyromonas gingivalis.
Knowledge on the host effects induced by a potential periodontal vaccine will
lead to the development of the therapeutic manipulation of effector function
leading to the amelioration or prevention of periodontal disease and associated
systemic diseases.
牙周病是宿主对
牙周病原体,如牙龈卟啉单胞菌。牙龈假单胞菌是一种
黑色素革兰氏阴性病原体,表现出各种毒力
与疾病有关的因素。该项目的总体目标是定义
诱导寄主反应的细胞机制(S)
预防牙龈假单胞菌感染。建议的研究将
专注于描述佐剂调节宿主的机制
对牙龈假单胞菌抗原的反应。重点将放在B7的作用
在宿主反应和牙龈假单胞菌感染中的共刺激分子,
以及细胞因子、特定靶细胞和其他细胞的参与
表面受体。具体来说,有以下计划:1)确定
赖氨酸特异性重组催化域的免疫原性研究
牙龈假单胞菌的Kgp(rKgp-CAT)和HagA重复结构域(RHArep),
霍乱毒素B亚单位(CTB)和单磷脂的作用
A(MPL)在调节鼻腔内对这些抗原的反应中的作用
免疫,诱导的抗体水平、亚型和免疫球蛋白亚类
用双抗体夹心法测定血清和外分泌物中的HArep或KGP-CAT。
CTB和MPL在增强/转移反应方面的作用将进一步增强
以测量抗原特异的增殖和细胞因子为特征的
制作。反应的效果,特别是反应的性质
抗体,在保护上也将被确定。2)确定机制
佐剂CTB和MPL通过其调节免疫诱导
回应。这些研究将确定共刺激蛋白B7的参与
佐剂和牙龈假单胞菌免疫增强能力中的分子
感染、受佐剂影响的靶细胞及其关联
在MPL、Toll样受体和B7共刺激分子之间。几组人
B7-L(B7-1-/-)、B7-2(B7-2J)或两者(B7-1/B7-2-/-)分子缺陷小鼠
正常对照组分别接种HArep或KGP-CAT。
CTB或MIPL。抗体和抗体分泌细胞的水平将是
采用ELISA法和ELISPOT法进行检测。佐剂对基因表达的影响
B7分子和CD4OL的含量将由FACS进行分析。差异化监管
对细胞因子诱导和增殖反应的影响也将进行评估。这个
将在#年评估B7共刺激在牙龈假单胞菌感染中的作用
B7基因缺陷小鼠。这些研究将通过以下方式提供有关机制的信息
哪些黏膜佐剂调节宿主免疫反应,靶细胞
通过它们的辅助性被发挥出来,并参与
B7分子和Toll样受体提供的共刺激信号。一个
对这些过程的理解对于开发方法至关重要
牙龈卟啉单胞菌干扰/预防牙周病的发病机制。
对潜在牙周疫苗引起的宿主效应的了解将
导致效应器功能的治疗手法的发展
导致改善或预防牙周病和相关的
系统性疾病。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Jannet Katz其他文献
Jannet Katz的其他文献
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{{ truncateString('Jannet Katz', 18)}}的其他基金
Mechanisms of Immune Modulation and Peridontal Disease
免疫调节与牙周疾病的机制
- 批准号:
6516680 - 财政年份:2001
- 资助金额:
$ 29.06万 - 项目类别:
Mechanisms of Immune Modulation and Periodontal Disease
免疫调节与牙周病的机制
- 批准号:
7422575 - 财政年份:2001
- 资助金额:
$ 29.06万 - 项目类别:
Mechanisms of Immune Modulation and Periodontal Disease
免疫调节与牙周病的机制
- 批准号:
6606156 - 财政年份:2001
- 资助金额:
$ 29.06万 - 项目类别:
Mechanisms of Immune Modulation and Periodontal Disease
免疫调节与牙周病的机制
- 批准号:
7568853 - 财政年份:2001
- 资助金额:
$ 29.06万 - 项目类别:
Mechanisms of Immune Modulation and Periodontal Disease
免疫调节与牙周病的机制
- 批准号:
7380161 - 财政年份:2001
- 资助金额:
$ 29.06万 - 项目类别:
Mechanisms of Immune Modulation and Periodontal Disease
免疫调节与牙周病的机制
- 批准号:
6760213 - 财政年份:2001
- 资助金额:
$ 29.06万 - 项目类别:
Mechanisms of Immune Modulation and Periodontal Disease
免疫调节与牙周病的机制
- 批准号:
8089431 - 财政年份:2001
- 资助金额:
$ 29.06万 - 项目类别:
Mechanisms of Immune Modulation and Periodontal Disease
免疫调节与牙周病的机制
- 批准号:
7851438 - 财政年份:2001
- 资助金额:
$ 29.06万 - 项目类别:
Mechanisms of Immune Modulation and Periodontal Disease
免疫调节与牙周病的机制
- 批准号:
6884589 - 财政年份:2001
- 资助金额:
$ 29.06万 - 项目类别:
MECHANISM(S) OF PROPHYROMONAS GINGIVALIS ADHERENCE
牙龈卟啉单胞菌的粘附机制
- 批准号:
6011653 - 财政年份:1999
- 资助金额:
$ 29.06万 - 项目类别:
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