受容体相互作用タンパク質2が先天的および適応的免疫反応に関与する
Arnold I Chin1, Paul W Dempsey, Kevin Bruhn
1Molecular Biology Institute, University of California, Los Angeles, California 90095, USA.
Nature
|March 15, 2002
まとめ
受容体相互作用タンパク質2 (Rip2) は,リステリアのような細胞内細菌に対する宿主防御に不可欠です. Rip2欠乏症は,免疫細胞の活性化とサイトカインの産生を阻害し,免疫におけるその役割を強調する.
科学分野:
- 免疫学 免疫学とは
- 分子生物学は分子生物学である.
- 微生物学 微生物学とは
背景:
- ホストの防御には,先天的および適応的免疫が含まれます.
- 細胞内細菌感染症では,マクロファージ,中性子,NK細胞,TH1細胞を活性化する.
- これらのプロセスにおける受容体相互作用タンパク質2 (Rip2) の役割は不明であった.
研究 の 目的:
- ホストの防衛機構における受容体相互作用タンパク質2 (Rip2) の生理学的役割を調査する.
- 細胞内病原体に対する免疫および炎症反応におけるRip2の機能を明らかにする.
主な方法:
- リップ2欠乏性のマウスの世代.
- マウスおよびマクロファージのリステリア・モノサイトゲネス感染.
- リポポリサッカリド (LPS) によるマクロファージの刺激.
- NF-kappaBの活性化,内毒性ショック抵抗,およびサイトカイン生成 (インターフェロン・ガンマ,インタールイキン-12) の分析.
- Tヘルパー1および自然キラー細胞におけるStat4活性化の評価.
主要な成果:
- リップ2欠乏したマウスは,リステリア・モノサイトゲネス感染と戦う能力が著しく低下したことを示した.
- Rip2欠乏したマウスのマクロファージは,L. monocytogenes感染またはLPS治療でNF-kappaBの活性化が低下した.
- 支配的陰性Rip2は,Toll型受容体4とNod1によって媒介されるNF-kappaBの活性化を阻害した.
- リップ2欠乏症のマウスは,致命的なLPS誘発の内毒性ショックに抵抗性がありました.
- リップ2欠乏マウスのTH1およびNK細胞において,インターレウキン12誘発のStat4活性化の欠陥に関連した,インターレウキンガマの生産障害が観察されました.
結論:
- Rip2は,細胞内細菌感染に対する宿主防御に不可欠です.
- Rip2は,TLR4とNod1を含むNF-kappaB活性化経路において重要な役割を果たしています.
- Rip2は,適切なインターフェロン・ガンマ産生とStat4活性化のために必要であり,TH1およびNK細胞機能に影響を与えます.
- これらの発見は,複数の免疫および炎症反応経路におけるRip2の必要性を強調しています.
関連する概念動画
Cell-mediated Immune Responses
Overview
NF-κB-dependent Signaling Pathway
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
Regulation of the Unfolded Protein Response
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
Antigens Involved in Adaptive Immunity
An antigen is any substance the immune system identifies as foreign and potentially harmful to the body, prompting an immune response. Antigens have two functional properties: immunogenicity and reactivity. Immunogenicity is the ability of an antigen to stimulate a specific immune response. At the same time, reactivity describes the antigen's ability to react with the cells and antibodies produced in response to it.
Complete Antigens
Complete antigens possess both immunogenicity and reactivity.
Complete Antigens
Complete antigens possess both immunogenicity and reactivity.
Diversity of Antigen Receptors
Antigen receptors are essential components of the immune system crucial in defending the body against foreign invaders. These receptors are present on the surface of B and T cells, enabling them to recognize antigens and mount an appropriate immune response.
Before encountering any antigen, lymphocytes express these receptors. On B cells, the antigen receptor is a membrane-bound antibody molecule called BCR; on T cells, it is a T cell receptor or TCR. B and T cell receptors are composed of two...
Before encountering any antigen, lymphocytes express these receptors. On B cells, the antigen receptor is a membrane-bound antibody molecule called BCR; on T cells, it is a T cell receptor or TCR. B and T cell receptors are composed of two...
Antigen Processing Pathways
MHC molecules are key players in the immune response, enabling T cells to recognize and respond to specific antigens. They are present on the surface of all nucleated cells in the body and are instrumental in presenting antigens to T cells and activating them. T cells recognize the MHC-antigen complex and initiate an immune response. MHC class I and MHC class II are two main types of MHC molecules, each associated with a distinct antigen processing pathway.
MHC Class I: Presenting Endogenous...
MHC Class I: Presenting Endogenous...


