查看“IL-2/IL-12”的源代码

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            <strong>[[IL-2]] 与 [[IL-12]]</strong> 是驱动<strong>[[细胞免疫]]</strong>应答的两大核心细胞因子。IL-2 主要作为 T 细胞的“燃料”，负责诱导 <strong>[[克隆扩增]]</strong> 和维持存活；而 IL-12 则作为“方向盘”，由抗原提呈细胞（APC）分泌，决定 T 细胞向 <strong>[[Th1 细胞]]</strong> 或 <strong>[[CTL (CD8+)]]</strong> 效应方向分化。两者在协同作用下，能够显著增强机体对病毒、胞内致病菌及肿瘤的防御能力。
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            <div style="font-size: 1.25em; font-weight: bold; letter-spacing: 1.2px;">IL-2 / IL-12 对比</div>
            <div style="font-size: 0.7em; opacity: 0.85; margin-top: 4px; white-space: nowrap;">细胞因子生化全参数</div>
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                <div style="font-size: 0.8em; color: #64748b; margin-top: 10px; font-weight: 600;">核心特性：协同增强 1 型应答</div>
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                    <td colspan="2" style="padding: 6px; border-bottom: 1px solid #e2e8f0;">白细胞介素-2 (IL-2)</td>
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                    <th style="text-align: left; padding: 6px 10px; background-color: #f8fafc; border-bottom: 1px solid #f1f5f9; width: 40%;">主要来源</th>
                    <td style="padding: 6px 10px; border-bottom: 1px solid #f1f5f9;">活化的 CD4+ & CD8+ T</td>
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                    <th style="text-align: left; padding: 6px 10px; background-color: #f8fafc; border-bottom: 1px solid #f1f5f9;">关键受体</th>
                    <td style="padding: 6px 10px; border-bottom: 1px solid #f1f5f9;">[[CD25]] (IL-2Rα), CD122, CD132</td>
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                    <th style="text-align: left; padding: 6px 10px; background-color: #f8fafc; border-bottom: 1px solid #f1f5f9;">信号通路</th>
                    <td style="padding: 6px 10px; border-bottom: 1px solid #f1f5f9;">JAK1/3 - [[STAT5]]</td>
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                    <td colspan="2" style="padding: 6px; border-bottom: 1px solid #e2e8f0;">白细胞介素-12 (IL-12)</td>
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                    <th style="text-align: left; padding: 6px 10px; background-color: #f8fafc; border-bottom: 1px solid #f1f5f9;">主要来源</th>
                    <td style="padding: 6px 10px; border-bottom: 1px solid #f1f5f9;">[[树突状细胞]], 巨噬细胞</td>
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                    <th style="text-align: left; padding: 6px 10px; background-color: #f8fafc; border-bottom: 1px solid #f1f5f9;">分子构成</th>
                    <td style="padding: 6px 10px; border-bottom: 1px solid #f1f5f9;">异源二聚体 (p35 + p40)</td>
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                    <th style="text-align: left; padding: 6px 10px; background-color: #f8fafc; border-bottom: 1px solid #f1f5f9;">信号通路</th>
                    <td style="padding: 6px 10px; border-bottom: 1px solid #f1f5f9;">JAK2/TYK2 - [[STAT4]]</td>
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                    <td colspan="2" style="padding: 6px; border-bottom: 1px solid #e2e8f0;">临床应用与结局</td>
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                    <th style="text-align: left; padding: 6px 10px; background-color: #f8fafc; border-bottom: 1px solid #f1f5f9;">核心效应</th>
                    <td style="padding: 6px 10px; border-bottom: 1px solid #f1f5f9;">产生 [[IFN-γ]], 促进 CTL 杀伤</td>
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                    <th style="text-align: left; padding: 6px 10px; background-color: #f8fafc; border-bottom: 1px solid #f1f5f9;">治疗用途</th>
                    <td style="padding: 6px 10px; border-bottom: 1px solid #f1f5f9; color: #1e40af;">肾癌、黑色素瘤、抗病毒</td>
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                    <th style="text-align: left; padding: 6px 10px; background-color: #f8fafc;">副作用</th>
                    <td style="padding: 6px 10px; color: #e11d48;">血管渗透综合征 (IL-2)</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;">功能分工：扩增燃料与极化引擎</h2>

    

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        在<strong>[[抗原刺激]]</strong>引发的级联反应中，IL-2 和 IL-12 分别在量级和质变上发挥作用：
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        <li style="margin-bottom: 12px;"><strong>IL-2 (T 细胞生长因子)：</strong> 作为<strong>[[自分泌]]</strong>或旁分泌因子，IL-2 结合高亲和力受体后，通过 <strong>[[Jak1]]</strong>-STAT5 通路诱导细胞进入周期分裂。它是 <strong>[[克隆扩增]]</strong> 规模的决定因素。</li>
        <li style="margin-bottom: 12px;"><strong>IL-12 (1 型免疫启动者)：</strong> IL-12 结合受体后激活 <strong>[[STAT4]]</strong>，上调主控转录因子 <strong>T-bet</strong> 的表达。这促使 CD4+ T 细胞极化为 <strong>[[Th1 细胞]]</strong>，并分泌 <strong>[[IFN-γ]]</strong>，进一步强化 CTL 的杀伤活性。</li>
        <li style="margin-bottom: 12px;"><strong>协同杀伤效应：</strong> 两者协同能极大程度上增强 NK 细胞和 <strong>[[细胞毒性 T 细胞 (CTL)]]</strong> 的细胞毒活性，并诱导其表达高水平的<strong>[[穿孔素]]</strong>与<strong>[[颗粒酶]]</strong>。</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;">调节逻辑：平衡效应与耐受</h2>

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                <th style="padding: 12px; border: 1px solid #cbd5e1; color: #0f172a; width: 25%;">调节机制</th>
                <th style="padding: 12px; border: 1px solid #cbd5e1; color: #475569;">IL-2 的角色</th>
                <th style="padding: 12px; border: 1px solid #cbd5e1; color: #1e40af;">IL-12 的角色</th>
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                <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">效应增强</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">维持效应细胞的长期存活与爆发力。</td>
                <td style="padding: 10px; border: 1px solid #cbd521;">诱导向“细胞毒性”表型的终末分化。</td>
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                <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">免疫耐受</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1; color: #1e40af;">必需于 <strong>[[Treg 细胞]]</strong> 的发育与功能（双刃剑）。</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">通常拮抗 Th2/Th17 的抑制或炎症。</td>
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                <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">负向反馈</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">通过 [[AICD]] (活化诱导凋亡) 清除多余细胞。</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">过量可能导致组织器官的严重炎症损伤。</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>Malek, T. R., & Castro, I. (2010).</strong> <em>Interleukin-2 receptor signaling: at the interface between tolerance and immunity.</em> <strong>Immunity</strong>, 33(2), 153-165.<br>
            <span style="color: #475569;">[点评]：系统论述了 IL-2 信号在促进免疫效应与维持 Treg 耐受之间的精密平衡。</span>
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            [2] <strong>Trinchieri, G. (2003).</strong> <em>Interleukin-12 and the regulation of innate resistance and adaptive immunity.</em> <strong>Nature Reviews Immunology</strong>, 3(2), 133-146.<br>
            <span style="color: #475569;">[点评]：IL-12 领域的权威文献，阐明了其连接固有免疫与适应性免疫的桥梁作用。</span>
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            [3] <strong>Liao, W., et al. (2013).</strong> <em>Interleukin-2 at the crossroads of effector responses, tolerance, and memory.</em> <strong>Nature Immunology</strong>, 14(3), 203-208.<br>
            <span style="color: #475569;">[点评]：详细解析了 IL-2 信号强度如何影响 T 细胞向记忆态或效应态转化的决策。</span>
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            <li style="margin-bottom: 8px;"><strong>[[IFN-γ]]：</strong> IL-12 信号诱导的最关键下游效应因子，也是 Th1 应答的标志。</li>
            <li style="margin-bottom: 8px;"><strong>[[CD25]]：</strong> IL-2R 的高亲和力链，其表达水平反映了 T 细胞的活化程度。</li>
            <li style="margin-bottom: 8px;"><strong>[[Jak1/Jak3]]：</strong> IL-2 信号转导所依赖的核心激酶对。</li>
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            IL-2 / IL-12 · 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;">分化指向</td>
                <td style="padding: 10px 15px; color: #334155;">[[Th1 极化]]•[[CTL 成熟]]•[[NK 细胞活化]]</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;">信号分子</td>
                <td style="padding: 10px 15px; color: #334155;">[[STAT4 (IL-12)]]•[[STAT5 (IL-2)]]•[[T-bet]]</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;">治疗领域</td>
                <td style="padding: 10px 15px; color: #334155;">[[过继性 T 细胞治疗]]•[[癌症疫苗]]•[[免疫检查点协同]]</td>
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