查看“Th1 细胞”的源代码

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            <strong>[[Th1 细胞]] (Type 1 Helper T Cells)</strong> 是 <strong>[[辅助性 T 细胞]]</strong> 的重要效应亚群，主要负责启动和协调针对胞内病原体（如病毒和胞内菌）的 <strong>[[细胞免疫]]</strong> 应答。其分化由 <strong>[[IL-12]]</strong> 驱动，并通过主控转录因子 <strong>[[T-bet]]</strong> 锁定表型。Th1 细胞的标志性特征是大量分泌 <strong>[[IFN-γ]]</strong>，这不仅能显著增强 <strong>[[巨噬细胞]]</strong> 的杀菌能力，还能通过提供“许可”信号协助 <strong>[[CD8+ T (CTL)]]</strong> 的活化与扩增。在病理状态下，Th1 细胞的过度活化与多种 <strong>[[自身免疫病]]</strong>（如克罗恩病、类风湿性关节炎）及慢性炎症密切相关。
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            <div style="font-size: 1.25em; font-weight: bold; letter-spacing: 1.2px;">Th1 细胞</div>
            <div style="font-size: 0.7em; opacity: 0.85; margin-top: 4px; white-space: nowrap;">Th1 Subtype · 核心档案</div>
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                <div style="font-size: 0.8em; color: #64748b; margin-top: 10px; font-weight: 600;">核心特性：1 型细胞应答指挥官</div>
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                    <td colspan="2" style="padding: 6px; border-bottom: 1px solid #e2e8f0;">分化与转录调控</td>
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                    <th style="text-align: left; padding: 6px 10px; background-color: #f8fafc; border-bottom: 1px solid #f1f5f9; width: 40%;">诱导细胞因子</th>
                    <td style="padding: 6px 10px; border-bottom: 1px solid #f1f5f9; color: #1e40af;">[[IL-12]], [[IFN-γ]]</td>
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                    <th style="text-align: left; padding: 6px 10px; background-color: #f8fafc; border-bottom: 1px solid #f1f5f9;">核心转录因子</th>
                    <td style="padding: 6px 10px; border-bottom: 1px solid #f1f5f9; color: #1e40af;">[[T-bet]], [[STAT4]]</td>
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                    <th style="text-align: left; padding: 6px 10px; background-color: #f8fafc; border-bottom: 1px solid #f1f5f9;">分化路径</th>
                    <td style="padding: 6px 10px; border-bottom: 1px solid #f1f5f9; color: #0f172a;">[[初始 T 细胞]] → Th1</td>
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                    <td colspan="2" style="padding: 6px; border-bottom: 1px solid #e2e8f0;">效应分子库</td>
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                    <th style="text-align: left; padding: 6px 10px; background-color: #f8fafc; border-bottom: 1px solid #f1f5f9;">特征细胞因子</th>
                    <td style="padding: 6px 10px; border-bottom: 1px solid #f1f5f9; color: #0f172a;">[[IFN-γ]], [[IL-2]], [[TNF-β]]</td>
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                    <th style="text-align: left; padding: 6px 10px; background-color: #f8fafc; border-bottom: 1px solid #f1f5f9;">关键膜分子</th>
                    <td style="padding: 6px 10px; border-bottom: 1px solid #f1f5f9; color: #0f172a;">CD40L (CD154), FasL</td>
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                    <td colspan="2" style="padding: 6px; border-bottom: 1px solid #e2e8f0;">生理与病理任务</td>
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                    <th style="text-align: left; padding: 6px 10px; background-color: #f8fafc; border-bottom: 1px solid #f1f5f9;">主要防御对象</th>
                    <td style="padding: 6px 10px; border-bottom: 1px solid #f1f5f9; color: #0f172a;">结核杆菌, 病毒, 肿瘤</td>
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                    <th style="text-align: left; padding: 6px 10px; background-color: #f8fafc;">典型相关疾病</th>
                    <td style="padding: 6px 10px; color: #e11d48;">[[迟发型超敏反应]], 克罗恩病</td>
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    <h2 style="background: #f1f5f9; color: #0f172a; padding: 10px 18px; border-radius: 0 6px 6px 0; font-size: 1.25em; margin-top: 40px; border-left: 6px solid #0f172a; font-weight: bold;">分化机制：从初始 T 细胞到 Th1 的极化</h2>

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        Th1 细胞的极化是 <strong>[[适应性免疫]]</strong> 应对胞内威胁的关键决策：
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        <li style="margin-bottom: 12px;"><strong>启动信号：</strong> 当 <strong>[[树突状细胞]]</strong> 摄取胞内病原体后，通过分泌 <strong>[[IL-12]]</strong> 为初始 T 细胞提供分化指令。</li>
        <li style="margin-bottom: 12px;"><strong>级联放大：</strong> IL-12 激活 <strong>[[STAT4]]</strong>，随后诱导 <strong>[[T-bet]]</strong> 表达。T-bet 是 Th1 的“主控制蛋白”，它能开启 <strong>[[IFN-γ]]</strong> 基因的转录，并上调 IL-12 受体 $\beta_2$ 链的表达，形成正反馈极化环路。</li>
        <li style="margin-bottom: 12px;"><strong>表型锁定：</strong> T-bet 还会同时抑制 Th2 相关基因（如 GATA3）的表达，确保应答不会发生“偏移”。</li>
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    <h2 style="background: #f1f5f9; color: #0f172a; padding: 10px 18px; border-radius: 0 6px 6px 0; font-size: 1.25em; margin-top: 40px; border-left: 6px solid #0f172a; font-weight: bold;">效应网络：如何清除病原体？</h2>

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                <th style="padding: 12px; border: 1px solid #cbd5e1; color: #0f172a; width: 25%;">目标细胞</th>
                <th style="padding: 12px; border: 1px solid #cbd5e1; color: #475569;">Th1 的中介作用</th>
                <th style="padding: 12px; border: 1px solid #cbd5e1; color: #1e40af;">最终生理效应</th>
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                <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[巨噬细胞]]</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">分泌 <strong>[[IFN-γ]]</strong> + 表达 <strong>CD40L</strong>。</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">激活杀菌酶系统，清除胞内寄生菌（如结核菌）。</td>
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                <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[CD8+ T (CTL)]]</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">分泌 <strong>[[IL-2]]</strong> + “许可” 树突状细胞。</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1; color: #1e40af;">驱动 CTL <strong>[[克隆扩增]]</strong> 与记忆建立。</td>
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                <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[B 细胞]]</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">诱导向 <strong>IgG1/IgG3</strong> 类别转换。</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">产生具有强 <strong>[[调理作用]]</strong> 和补体活化能力的抗体。</td>
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    <h2 style="background: #f1f5f9; color: #0f172a; padding: 10px 18px; border-radius: 0 6px 6px 0; font-size: 1.25em; margin-top: 40px; border-left: 6px solid #0f172a; font-weight: bold;">权威学术文献与点评</h2>

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        <span style="color: #0f172a; font-weight: bold; font-size: 1.05em; display: inline-block; margin-bottom: 15px;">学术参考文献 [Academic Peer Review]</span>
        
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            [1] <strong>Szabo, S. J., et al. (2000).</strong> <em>A novel transcription factor, T-bet, directs Th1 lineage commitment.</em> <strong>Cell</strong>, 100(6), 655-669.<br>
            <span style="color: #475569;">[点评]：发现 T-bet 的开创性论文，确立了 Th1 谱系发育的分子遗传学标准。</span>
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            [2] <strong>Zhu, J., et al. (2010).</strong> <em>Differentiation of effector CD4+ T cell populations.</em> <strong>Annual Review of Immunology</strong>, 28, 445-489.<br>
            <span style="color: #475569;">[点评]：对 Th1、Th2 等亚群分化机制最详尽的系统综述，涵盖了细胞因子信号网络。</span>
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            [3] <strong>Mosmann, T. R., & Coffman, R. L. (1989).</strong> <em>TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties.</em> <strong>Annual Review of Immunology</strong>, 7(1), 145-173.<br>
            <span style="color: #475569;">[点评]：Th1/Th2 极化假说的起源，定义了现代细胞免疫学的基本框架。</span>
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    <h2 style="background: #f1f5f9; color: #0f172a; padding: 10px 18px; border-radius: 0 6px 6px 0; font-size: 1.25em; margin-top: 40px; border-left: 6px solid #0f172a; font-weight: bold;">关键相关概念</h2>
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            <li style="margin-bottom: 8px;"><strong>[[IFN-γ]]：</strong> Th1 的核心效应因子，激活巨噬细胞的溶酶体和氧化杀伤。</li>
            <li style="margin-bottom: 8px;"><strong>[[迟发型超敏反应]] (DTH)：</strong> Th1 细胞过度介导的组织损伤典型表现。</li>
            <li style="margin-bottom: 8px;"><strong>[[Th1/Th2 平衡]]：</strong> 决定机体应答偏向以及对特定病原体易感性的生理平衡。</li>
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            Th1 细胞 · 知识图谱
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                <td style="width: 110px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 12px; text-align: right; vertical-align: middle; white-space: nowrap;">驱动激酶轴</td>
                <td style="padding: 10px 15px; color: #334155;">[[IL-12R]]•[[Jak2]]/[[Tyk2]]•[[STAT4]]•[[STAT1]]</td>
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                <td style="width: 110px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 12px; text-align: right; vertical-align: middle; white-space: nowrap;">效应通路</td>
                <td style="padding: 10px 15px; color: #334155;">[[IFN-γ 释放]]•[[CD40L 表达]]•[[IL-2 旁分泌]]</td>
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                <td style="width: 110px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 12px; text-align: right; vertical-align: middle; white-space: nowrap;">临床靶向</td>
                <td style="padding: 10px 15px; color: #334155;">[[IFN-γ 抑制剂]]•[[IL-12 单抗]]•[[T-bet 拮抗研究]]</td>
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