REGULATION OF ANTIGEN SPECIFIC SALIVARY IMMUNE RESPONSES
REGULATION OF ANTIGEN SPECIFIC SALIVARY IMMUNE RESPONSES
批准号:
2015518
负责人:
Kohtaro Fujihashi
金额:
$9.31万
依托单位国家:
美国
项目类别:
财政年份:
1997
资助国家:
美国
项目状态:
已结题
起止时间:
1997-04-01 至 2002-02-28
关键词:
CD4 molecule T cell receptor T lymphocyte acinar cell antibody formation antibody specificity antigen antibody reaction antigen presentation cell cell interaction cellular immunity cholera toxin cytokine enzyme linked immunosorbent assay epithelium flow cytometry genetic manipulation immunoglobulin A immunoglobulin E laboratory mouse microorganism immunology mucosal immunity polymerase chain reaction salivary glands secretory immune system
中文摘要
这项资助的一个主要目标是阐明潜在的分子和
诱导和调节抗原特异性
分泌型伊加(S-IgA)免疫反应在粘膜表面,重点
对唾液腺的影响S-IgA抗体的诱导是一个重要的手段
被认为是免疫系统的主要第一道防线
防止病原微生物通过粘膜表面侵入
区由于唾液是一种外部分泌物的突出例子,
含有S-IgA,重要的是要检查免疫机制
对于这种重要的防御因子的诱导和调节,
粘膜相关组织,重点是唾液腺。本
最后,我们的总体假设是,粘膜T细胞互联网存在,
γ-δ、α-β T细胞和腺泡/上皮细胞及其
衍生的细胞因子以及细胞与细胞的接触都起着重要的作用
在抗原特异性S-IgA抗体的诱导和调节中
应答因此,这种粘膜T细胞和腺泡/上皮细胞互联网
可能是一个关键因素,桥梁后天免疫和先天免疫,
在粘膜表面形成保护性防御。为了
为了实现我们的主要目标,这项赠款提案包括五个
具体目标。我们的重点将集中在分子和细胞
诱导和调节抗原的机制[例如,卵白蛋白
(0 VA)]特异性伊加合成。因此我们
将使用众所周知的粘膜佐剂霍乱毒素(CT)以诱导
唾液腺中抗原特异性S-IgA反应
应用程序.特别是,基因操作的突变CT将是一个焦点
为了比较Th 1型和Th 2型的调节,
用于诱导抗原特异性粘膜伊加的细胞因子产生,
针对野生型CT的全身性IgE免疫应答。γ-δ T的作用
用于调节粘膜伊加和系统性IgE的细胞也将被
研究了特别是,我们的具体目标分为:
五个组成部分。第一个目的是评估遗传
用于粘膜佐剂活性以诱导抗原特异性S-
唾液和颌下腺(SMG)中的伊加反应;第二个目的是
抗原(OVA)特异性CD 4 + Th 1和Th 2细胞应答的特征
通过用OVA加CT突变体鼻内免疫在SMG中诱导,
粘膜佐剂;第三个目的是测试唾液腺腺泡是否
/上皮细胞和/或γ-δ T细胞可以调节CD 4+,α-
用于表达Th 2-细胞因子的β T细胞(例如,IL-5和IL-6)
抗原特异性伊加B细胞应答;第四个目的是;确定
腺泡间三联体细胞间相互作用的可能机制
/上皮细胞、γ-δ T细胞和CD 4+、α-β T细胞,
细胞因子和细胞表面分子;第五个目的是检查
γ-δ T细胞对调节唾液伊加和
使用TCR δ和TCR β基因破坏小鼠的全身性IgE应答。
英文摘要
A major goal of this grant is to elucidate the underlying molecular and
cellular mechanisms for the induction and regulation of antigen-specific
secretory IgA (S-IgA) immune responses at mucosal surfaces with emphasis
on salivary gland. The induction of S-IgA antibodies is an important arm
of the immune system and is considered to be a major first line of defense
against invasion of pathogenic microorganisms through the mucosal surface
area. Since saliva is a prominent example of an external secretions
containing S-IgA, it is important to examine the immunological mechanisms
for the induction and regulation of this important defense factors in
mucosa-associated tissues, with emphasis on the salivary glands. To this
end, our overall hypothesis is that a mucosal T cell internet exists where
gamma-delta, alpha-beta T cells and acinar/ epithelial cells and their
derived cytokines as well as cell-to-cell contact all play an major role
in the induction and regulation of antigen-specific S-IgA antibodies
responses. Thus, this mucosal T cell and acinar / epithelial cell internet
may be a key element which bridges acquired and innate immunity for the
development of a protective defense at mucosal surfaces. For the purpose
of accomplishing our major goal, this grant proposal consists of five
specific aims. Our emphasis will be focused on the molecular and cellular
mechanisms for the induction and regulation of antigen [e.g., ovalbumin
(OVA)] -specific IgA synthesis by the mucosal T cell internet. Thus, we
will use well known mucosal adjuvant, cholera toxin (CT) in order to induce
antigen-specific S-IgA responses in salivary gland for this grant
application. Especially, genetically manipulated mutant CT will be a focus
of the grant in order to compare the modulation of Th1- and Th2-type
cytokine production for the induction of antigen-specific mucosal IgA and
systemic IgE immune responses to wild type CT. The role of gamma-delta T
cells for the regulation of mucosal IgA and systemic IgE will also be
investigated. In particular, our specific aims are divided into the
following five components. The first aim is the assess of genetically
manipulated CT for mucosal adjuvant activity to induce antigen-specific S-
IgA responses in saliva and submandibular gland (SMG) ; the second aim is
characterize of antigen (OVA) -specific CD4+ Th1 and Th2 cell responses
induced in SMG by intranasal immunization with OVA plus CT mutants as
mucosal adjuvants; the third aim is to test whether salivary gland acinar
/epithelial cells and / or gamma-delta T cells can regulate CD4+, alpha-
beta T cells for the expression of Th2-cytokines (e.g., IL-5 and IL-6) for
antigen-specific IgA B cell responses; the fourth aim is to; determine
possible mechanism(s) for triad cell-to-cell interactions among acinar
/epithelial cells, gamma-delta T cells and CD4+, alpha-beta T cells via
cytokine(s) and cell surface molecule(s); the fifth aim is to examine the
contribution of gamma-delta T cells for the regulation salivary IgA and
systemic IgE responses using TCRdelta and TCRbeta gene disrupted mice.
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会议论文
ADENOVIRUS FLT3 LIGAND INDUCES NALT DCs FOR SALIVARY GLAND S-lgA Ab RESPONSES
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批准号:7840769
-
项目类别:
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资助金额:$1.69万
-
财政年份:2009
-
负责人:Kohtaro Fujihashi
-
依托单位:
NALT-BASED ADJUVANTS FOR MUCOSAL IMMUNITY IN AGING
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批准号:7038822
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项目类别:
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资助金额:$29.18万
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财政年份:2006
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负责人:Kohtaro Fujihashi
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依托单位:
NALT-BASED ADJUVANTS FOR MUCOSAL IMMUNITY IN AGING
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批准号:7904801
-
项目类别:
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资助金额:$28.0万
-
财政年份:2006
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负责人:Kohtaro Fujihashi
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依托单位:
NALT-BASED ADJUVANTS FOR MUCOSAL IMMUNITY IN AGING
-
批准号:7475766
-
项目类别:
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资助金额:$28.29万
-
财政年份:2006
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负责人:Kohtaro Fujihashi
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依托单位:
NALT-BASED ADJUVANTS FOR MUCOSAL IMMUNITY IN AGING
-
批准号:7291544
-
项目类别:
-
资助金额:$28.86万
-
财政年份:2006
-
负责人:Kohtaro Fujihashi
-
依托单位:
NALT-BASED ADJUVANTS FOR MUCOSAL IMMUNITY IN AGING
-
批准号:7666083
-
项目类别:
-
资助金额:$28.29万
-
财政年份:2006
-
负责人:Kohtaro Fujihashi
-
依托单位:
Ab5 Toxins Nasal Adjuvant Target the Olfactory Bulbs/CNS
-
批准号:6711826
-
项目类别:
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资助金额:$25.11万
-
财政年份:2001
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负责人:Kohtaro Fujihashi
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依托单位:
ADENOVIRUS FLT3 LIGAND INDUCES NALT DCs FOR SALIVARY GLAND S-lgA Ab RESPONSES
-
批准号:7848986
-
项目类别:
-
资助金额:$34.43万
-
财政年份:1997
-
负责人:Kohtaro Fujihashi
-
依托单位:
REGULATION OF ANTIGEN SPECIFIC SALIVARY IMMUNE RESPONSES
-
批准号:2882731
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项目类别:
-
资助金额:$10.11万
-
财政年份:1997
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负责人:Kohtaro Fujihashi
-
依托单位:
REGULATION OF ANTIGEN SPECIFIC SALIVARY IMMUNE RESPONSES
-
批准号:2668269
-
项目类别:
-
资助金额:$9.45万
-
财政年份:1997
-
负责人:Kohtaro Fujihashi
-
依托单位:
A ROLE FOR INNATE IMMUNITY IN SALIVARY IgA RESPONSES
-
批准号:6621930
-
项目类别:
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资助金额:$28.13万
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财政年份:1997
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负责人:Kohtaro Fujihashi
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依托单位:
A ROLE FOR INNATE IMMUNITY IN SALIVARY IgA RESPONSES
-
批准号:6697270
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项目类别:
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资助金额:$28.13万
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财政年份:1997
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负责人:Kohtaro Fujihashi
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依托单位:
ADENOVIRUS FLT3 LIGAND INDUCES NALT DCs FOR SALIVARY GLAND S-lgA Ab RESPONSES
-
批准号:7467392
-
项目类别:
-
资助金额:$34.78万
-
财政年份:1997
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负责人:Kohtaro Fujihashi
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依托单位:
A ROLE FOR INNATE IMMUNITY IN SALIVARY IgA RESPONSES
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批准号:6828233
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项目类别:
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资助金额:$28.13万
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财政年份:1997
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负责人:Kohtaro Fujihashi
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依托单位:
ADENOVIRUS FLT3 LIGAND INDUCES NALT DCs FOR SALIVARY GLAND S-lgA Ab RESPONSES
-
批准号:7643321
-
项目类别:
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资助金额:$34.78万
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财政年份:1997
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负责人:Kohtaro Fujihashi
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依托单位:
REGULATION OF ANTIGEN SPECIFIC SALIVARY IMMUNE RESPONSES
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批准号:6164421
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项目类别:
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资助金额:$10.51万
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财政年份:1997
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负责人:Kohtaro Fujihashi
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依托单位:
REGULATION OF ANTIGEN SPECIFIC SALIVARY IMMUNE RESPONSES
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批准号:6362931
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项目类别:
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资助金额:$10.93万
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财政年份:1997
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负责人:Kohtaro Fujihashi
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依托单位:
A ROLE FOR INNATE IMMUNITY IN SALIVARY IgA RESPONSES
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批准号:6989079
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项目类别:
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资助金额:$27.47万
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财政年份:1997
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负责人:Kohtaro Fujihashi
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依托单位:
A ROLE FOR INNATE IMMUNITY IN SALIVARY IgA RESPONSES
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批准号:6437846
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项目类别:
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资助金额:$33.84万
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财政年份:1997
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负责人:Kohtaro Fujihashi
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依托单位:
CELLULAR AND MOLECULAR MECHANISMS FOR MUCOSAL IMMUNITY
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批准号:6750073
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项目类别:
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资助金额:$28.7万
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财政年份:1982
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负责人:Kohtaro Fujihashi
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依托单位:
海外基金