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href="#related-articles">相关文章</一个> </div> </div> </div> </div> </div> <div class="ant-col ThreeColumnLayout_middleColumn__sbd41"> <div class="ArticleMiddleSection_articleMiddleSection__gAv9z"> <div class="articleHeader"> <div class="articleHeader__specialIssue"> <span class="articleHeader__specialIssue_tag">特殊的问题</年代pan> <h2 class="articleHeader__specialIssue_title">免疫系统建模和相关疾病</gydF4y2Bah2> <a href="//www.newsama.com/journals/cmmm/si/650367/" class="articleHeader__specialIssue_url" target="_blank" rel="noreferrer">把这个特殊的问题</一个> </div> <strong>研究文章|<gydF4y2Ba!-- -->开放获取</年代trong> <div class="articleHeader__meta"> <span>体积<gydF4y2Ba!-- -->2012年<gydF4y2Ba!-- -->|</年代pan> <span>文章的ID<gydF4y2Ba!-- -->842329年<gydF4y2Ba!-- -->|</年代pan> <span class="articleHeader__meta_doiLink"><a href="https://doi.org/10.1155/2012/842329" aria-label="Doi-link" target="_blank" rel="noreferrer">https://doi.org/10.1155/2012/842329</一个></span> </div> <div class="simpleShowMore"> <button class="simpleShowMore__button">显示引用</gydF4y2Babutton> </div> <h1 class="articleHeader__title">'之间的时间间隔,提高注入如何影响免疫系统的免疫反应在计算模型</gydF4y2Bah1> <div class="articleHeader__authors"> <span class="articleHeader__authors_author"><strong>f·卡斯特隆</年代trong><a href="//www.newsama.com/cdn-cgi/l/email-protection" aria-label="Mail Option"><span role="img" class="anticon"> <svg version="1.0" xmlns="http://www.w3.org/2000/svg" width="1em" height="1em" viewbox="0 0 1401 1101"> <path fill="#6ba439" d="M132.5 2.1C101.4 6 71.1 20.5 48.3 42.4c-22.7 21.7-37.5 48.3-44.6 80l-2.2 10.1v837l2.2 10.1c6.7 30 19.3 53.9 39.8 75.3 23.3 24.3 56.4 40.9 90 45 12.8 1.6 1122.2 1.6 1135 0 38.9-4.8 75.9-25.6 100-56.4 15-19.3 24.2-39 29.8-63.9l2.2-10.1v-837l-2.2-10.1c-7.1-31.8-21.9-58.3-44.6-80.1-20.2-19.2-43.9-31.7-73.6-38.5l-9.6-2.3L705 1.4c-321.9-.1-568.5.2-572.5.7zm1123.4 99.5c1.7.4 3.1 1 3.1 1.4 0 .5-125.6 87.7-279 194L700.9 490.2 422 297C268.5 190.7 143 103.4 143 103c0-.5 1-1.1 2.3-1.3 3.5-.7 1107.1-.8 1110.6-.1zM401 404c164.4 113.8 299.4 207 300 207 .6 0 135.6-93.2 300.1-207 164.5-113.9 299.3-207 299.5-207 .2 0 .4 170.9.4 379.7 0 417.9.5 386-6.1 398.3-6.2 11.6-19 21.4-31.9 24.4-5.8 1.4-67.4 1.6-562 1.6s-556.2-.2-562-1.6c-12.9-3-25.7-12.8-31.9-24.4-6.6-12.3-6.1 19.6-6.1-398.3 0-208.8.2-379.7.5-379.7S236.6 290.1 401 404z"></path> </svg></span></a>,<年代up>1</年代up></span> <span class="articleHeader__authors_author">f . Mantile<gydF4y2Ba!-- -->,<年代up>2</年代up></span> <span class="articleHeader__authors_author">p . De Berardinis<gydF4y2Ba!-- -->,<年代up>3</年代up></span> <span class="articleHeader__authors_author">和<gydF4y2Ba!-- -->答:Prisco<年代up>2</年代up></span> </div> <div class="simpleShowMore"> <button class="simpleShowMore__button">显示更多</gydF4y2Babutton> </div> <div class="articleHeader__academicEditor"> <strong>学术编辑器:</年代trong> <span>弗朗西斯科·搜集</年代pan> </div> <div class="articleHeader__timeline"> <div class="articleHeader__timeline_item "> <strong>收到了</年代trong> <span>2012年6月15日</年代pan> </div> <div class="articleHeader__timeline_item "> <strong>接受</年代trong> <span>2012年7月23日</年代pan> </div> <div class="articleHeader__timeline_item articleHeader__timeline_item_sticky"> <strong>发表</年代trong> <span>2012年9月11日</年代pan> </div> </div> </div> <div class="articleBody"> <div class="xml-content"> <h4 class="header" id="abstract">文摘</gydF4y2Bah4> <p>免疫系统能够更积极地回应到第二个比第一个接触特定抗原接触。接种疫苗的协议通常包括至少两个剂量,为了获得高的抗体滴度。我们要分析之间的关系时间从第一剂量(启动)和第二剂量(提高)抗体滴度。在本文中,我们夫妇<gydF4y2Bai>在活的有机体内</gydF4y2Bai>实验与计算机模拟来评估推迟第二注入的影响。我们观察到一个间隔之间的几周总理和提高抗体反应的优化是必要的。</gydF4y2Bap> <span class="end-abs"></span> <h4 id="introduction">1。介绍</gydF4y2Bah4> <p>免疫记忆,定义为免疫系统的能力,更积极地应对第二次接触特定抗原比第一次接触,是提供的持久保护的基础的解决一些感染和疫苗接种的目标。记忆是一种免疫系统的系统级属性,它起源于增加抗原特异性B和T细胞的频率以及抗原特异性淋巴细胞的分化成记忆细胞,能够迅速做出反应,抗原和自我更新(<一个href="#B1">1</一个>- - - - - -<一个href="#B3">3</一个>]。</gydF4y2Bap> <p>所提供的保护,导致目前使用的疫苗与抗体反应的大小相关。抗原抗体滴度的持久性保护阈值和表现出的能力“回忆反应”与抗原eencounter一直是唯一的可测量的相关疫苗”采取“和免疫记忆。然而,这些方法的评价免疫记忆受到依赖长期监测的缺点的免疫反应。因此,优化疫苗接种计划获得高和持久化抗体滴度,一个重要的步骤在新型疫苗和免疫疗法的发展,是一个长期反复试验的过程(<一个href="#B4">4</一个>,<一个href="#B5">5</一个>]。</gydF4y2Bap> <p>免疫反应的大小通常可以增加了多个政府疫苗;所代表的例外virus-vectored疫苗和由此引发的免疫病毒衣壳第一剂量可以防止细胞感染随后的剂量。</gydF4y2Bap> <p>当一个新的原型疫苗首次测试<gydF4y2Bai>在活的有机体内</gydF4y2Bai>,注射安排设计经验,通过结合免疫学的知识,经验,和实际的约束,它是精致的基础上观察到的免疫反应和保护。然而,<gydF4y2Bai>在活的有机体内</gydF4y2Bai>实验提出了实用的限制不同免疫程序的数量,可以试图找到最大化抗体效价的协议,同时最小化剂量的数量。因此,<gydF4y2Bai>在网上</gydF4y2Bai>模拟动力学的抗体反应可以生成的预测,可以通过实验测试,生成新的假设早期相关免疫记忆。</gydF4y2Bap> <p>疫苗用于生成报告的实验数据研究和描述的部分<一个href="#sec2">2</一个>,即- E2(1 - 11),由“病毒样颗粒”由一个域的细菌蛋白E2能够自组装成60米肽(<一个href="#B6">6</一个>]。每个粒子表面显示60份肽”DAEFRHDSGYE”,对应于第一个11β-淀粉样蛋白的氨基端残留,形成肽聚集在阿尔茨海默氏症患者的大脑。</gydF4y2Bap> <p>单个“'”(1 - 11)E2的剂量疫苗诱发anti-beta-amyloid抗体的滴度测量在所有治疗的老鼠,老鼠在4/5,收到了“促进”剂量6个月后,我们观察到一个清晰的记忆的反应,也就是说,一个快速的崛起anti-beta-amyloid抗体滴度之间的血清浓度峰值1和7毫克/毫升。</gydF4y2Bap> <p>研究表现在阿尔茨海默病转基因小鼠模型表明,β-淀粉样蛋白抗体能够减少斑块和改善认知(了<一个href="#B7">7</一个>- - - - - -<一个href="#B10">10</一个>]。在小鼠模型以及阿尔茨海默氏症患者在临床试验中,感应anti-beta-amyloid抗体效价高的与疫苗接种的治疗效果<一个href="#B10">10</一个>,<一个href="#B11">11</一个>]。</gydF4y2Bap> <p>在这项研究中,时间延迟的影响之间的第一个和第二个注入峰上的抗原抗体效价是探索在一个计算机模型免疫系统的反应。</gydF4y2Bap> <h4 id="materials-and-methods">2。材料和方法</gydF4y2Bah4> <h5 id="sec2.1">2.1。动物</gydF4y2Bah5> <p>BALB / c小鼠从查尔斯河实验室获得意大利。伦理委员会的机构内工作进行批准的协议涉及老鼠和这些符合赫尔辛基宣言的规定和意大利国家动物用于研究指南。</gydF4y2Bap> <h5 id="sec2.2">2.2。代的病毒样颗粒(车牌区域)E2 (1 - 11)</gydF4y2Bah5> <p>合成互补的寡核苷酸编码序列1 - 11(序列DAEFRHDSGYE)的β-淀粉样蛋白被克隆到pETE2DISP向量减少NcoI和XmaI获得质粒宠物E2 (1 - 11)。成功建设的质粒DNA序列分析证实了。(1 - 11)是生产和E2车牌区域特征(如前所述)(<一个href="#B5">5</一个>]。</gydF4y2Bap> <h5 id="sec2.3">2.3。免疫接种</gydF4y2Bah5> <p>与200年小鼠腹腔免疫<年代vg height="9.6750002" id="M1" style="vertical-align:-2.29482pt;width:9.6374998px;" version="1.1" viewbox="0 0 9.6374998 9.6750002" width="9.6374998" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,9.675)"> <g transform="translate(72,-64.26)"> <text transform="matrix(1,0,0,-1,-71.95,66.6)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> </text> </g> </g> </svg>L 1: 1的混合抗原和佐剂。完全弗氏佐剂(CFA)是用于第一次注射,和不完全弗氏佐剂(IFA)在第二个。每个老鼠收到了大量的抗原携带6<年代vg height="9.6750002" id="M2" style="vertical-align:-2.29482pt;width:9.6374998px;" version="1.1" viewbox="0 0 9.6374998 9.6750002" width="9.6374998" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,9.675)"> <g transform="translate(72,-64.26)"> <text transform="matrix(1,0,0,-1,-71.95,66.6)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> </text> </g> </g> </svg>β-淀粉样蛋白抗原决定基的g。血液是在表示时间点采集,ELISA进行血清。</gydF4y2Bap> <h5 id="sec2.4">2.4。酶联免疫吸附试验(ELISA)</gydF4y2Bah5> <p>井96井Nunc Immunoplate被涂上一层链霉亲和素37°C /晚上直到完全蒸发。井被封锁0.5%牛血清白蛋白在20毫米TrisHCl pH值7.3,120毫米氯化钠,孵化与50 ng生物素化的肽,孵化与小鼠血清稀释0.25%牛血清白蛋白,20毫米TrisHCl pH值7.3,0.5 M氯化钠,渐变20 0.05%,检测与anti-mouse免疫球蛋白过氧化物酶共轭(σ- 2554)。</gydF4y2Bap> <p>孵化项目都进行了1小时在37°C,和每一步后井与Elisa洗两次洗缓冲区(EWB)(20毫米TrisHCl pH值7.3,130毫米氯化钠,0.05%渐变20)和三羟甲基氨基甲烷缓冲液一次盐水(TBS)(20毫米TrisHCl pH值7.3,0.5 M氯化钠)。在室温下井孵化了45分钟和0.4毫克毫升<年代up>−1</年代up>30毫米O-phenylenediamine盐酸盐溶于柠檬酸,70毫米<年代vg height="14.6" id="M3" style="vertical-align:-3.13504pt;width:61.525002px;" version="1.1" viewbox="0 0 61.525002 14.6" width="61.525002" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,14.6)"> <g transform="translate(72,-60.32)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> N</t年代pan> <tspan style="font-size: 12.50px; " x="8.8021116" y="0"> 一个</t年代pan> </text> <text transform="matrix(1,0,0,-1,-57.6,60.37)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 2</t年代pan> </text> <text transform="matrix(1,0,0,-1,-52.72,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> H</t年代pan> <tspan style="font-size: 12.50px; " x="9.0271664" y="0"> P</t年代pan> <tspan style="font-size: 12.50px; " x="15.991337" y="0"> O</t年代pan> </text> <text transform="matrix(1,0,0,-1,-27.7,60.37)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 4</t年代pan> </text> </g> </g> </svg>,0.8毫米<年代vg height="14.6" id="M4" style="vertical-align:-3.13504pt;width:34.875px;" version="1.1" viewbox="0 0 34.875 14.6" width="34.875" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,14.6)"> <g transform="translate(72,-60.32)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> H</t年代pan> </text> <text transform="matrix(1,0,0,-1,-62.92,60.37)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 2</t年代pan> </text> <text transform="matrix(1,0,0,-1,-58.05,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> O</t年代pan> </text> <text transform="matrix(1,0,0,-1,-49.02,60.37)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 2</t年代pan> </text> </g> </g> </svg>。吸光度是阅读在492 nm,阻塞后颜色发展受阻0.8硫酸。</gydF4y2Bap> <p>每个血清测试对β-淀粉样蛋白的合成肽1 - 11(β-淀粉样蛋白的合成肽23-29被用作负控制)。血清效价的定义为最高稀释的吸光度值等于双重背景值的获得对一个无关紧要的抗原。</gydF4y2Bap> <h5 id="sec2.5">2.5。计算模型</gydF4y2Bah5> <p>的<gydF4y2Bai>在网上</gydF4y2Bai>实验是由免疫系统的计算模型(<一个href="#B12">12</一个>使用二进制字符串来表示)<gydF4y2Bai>结合位点</gydF4y2Bai>细胞和分子(即。,lymphocytes receptors, BCRs, TCRs, Major Histocompatibility Complexes MHC, antigen peptides and epitopes, immunocomplexes IC, etc.).</p> <p>基于主体建模的模型是基于(ABM)范式,在所有实体都分别代表<一个href="#B13">13</一个>,<一个href="#B14">14</一个>在元胞自动机模型(<一个href="#B17">15</一个>]。它包括淋巴细胞谱系的主要类,也就是说,辅助T淋巴细胞,细胞毒性T淋巴细胞、B淋巴细胞,antibody-producer浆细胞和自然杀伤细胞(NK)和一些骨髓血统,巨噬细胞(M<年代vg height="13.425" id="M5" style="vertical-align:-2.29482pt;width:10.2px;" version="1.1" viewbox="0 0 10.2 13.425" width="10.2" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,13.425)"> <g transform="translate(72,-61.26)"> <text transform="matrix(1,0,0,-1,-71.95,63.6)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> </text> </g> </g> </svg>)和树突状细胞(DC)。这些实体合作后一组算法(或逻辑规则)进行免疫识别和响应的不同阶段一个通用的病原体。特别是,模型考虑吞噬作用,抗原,细胞因子释放,细胞激活不活跃或无能状态活跃状态,细胞毒性,抗体分泌。模型模拟的简化形式的先天免疫和适应性免疫的更复杂的形式,包括体液和细胞毒性免疫反应(<一个href="#B15">16</一个>]。</gydF4y2Bap> <p>在模型中,一个人类淋巴结(或它的一部分)映射到三维椭球笛卡尔网格。初级淋巴器官胸腺和骨髓相距建模:胸腺(<一个href="#B18">17</一个>是隐式地代表的积极和消极的选择之前不成熟的胸腺细胞进入淋巴系统,而骨髓生成已经成熟的B淋巴细胞。因此,只有免疫活性的淋巴细胞在初级淋巴器官建模。</gydF4y2Bap> <p>该计算模型可以被看作是一组工作的假设或理论,其中大部分被视为建立免疫机制。在细节,模型包括:伯内特的克隆选择理论(<一个href="#B16">18</一个>];Jerne [idiotypic网络理论<一个href="#B19">19</一个>];克隆删除(即理论。,thymus education of T lymphocytes, [<一个href="#B20">20.</一个>]);抗体的hypermutation [<一个href="#B21">21</一个>];的危险理论Matzinger [<一个href="#B22">22</一个>];复制衰老T细胞,或海弗利克极限(即。,细胞分裂数的限制,(<一个href="#B23">23</一个>]);t细胞无力(<一个href="#B24">24</一个>];Ag-dose-induced公差在B细胞(<一个href="#B25">25</一个>]。这些特性可以选择性地开启或关闭,允许一般免疫假说的调查。此外,其他特定生物学过程可以被添加到模型以相对较少的努力。例如,定制的基本模型被用来模拟不同的现象从病毒感染(如艾滋病、EBV [<一个href="#B26">26</一个>,<一个href="#B27">27</一个>])I型超敏反应(<一个href="#B28">28</一个>)和癌症(<一个href="#B29">29日</一个>,<一个href="#B30">30.</一个>]。</gydF4y2Bap> <p>一个模拟时间步相当于八小时。细胞之间的相互作用决定他们的功能行为(表<一个href="//www.newsama.com/journals/cmmm/2012/842329/tab1/" target="_blank">1</一个>)。交互是编码为概率规则定义的每个单元实体从一个状态过渡到另一个地方。每个交互都需要涉及细胞实体处于特定状态的一组可能的状态(例如,天真,活跃,休息,复制)是依赖于细胞类型。一旦这些条件都满足,交互是由一个概率,直接相关的有效水平的配体和受体之间的绑定。</gydF4y2Bap> <div class="floats-partial-section partial-other-wrapper" data-section="tab1"> <div class="floats-partial-footer"> <div class="floats-partial-caption"> <span class="caption-text">表1</年代pan> <a aria-label="View full page" class="caption-partial-url" href="//www.newsama.com/journals/cmmm/2012/842329/tab1/" title="" target="_blank"></a> </div> <div class="floats-partial-caption-text"> 生物规则编码细胞之间或细胞和分子之间的相互作用和其他特定的免疫系统的机制。每个条目的列表对应一种算法实现一个特定的免疫细胞的活动。</gydF4y2Badiv> <a class="table-thumb-overlay" href="//www.newsama.com/journals/cmmm/2012/842329/tab1" target="_blank" aria-label="View full page"></a> </div> </div> <p>字符串使用0和1来表示特异性受体和其它分子特异性结合等元素(参见图<一个href="//www.newsama.com/journals/cmmm/2012/842329/fig1/" target="_blank">1</一个>)。这个字符串的长度被指定为一个参数<年代vg height="11.0375" id="M12" style="vertical-align:-0.13794pt;width:9.1750002px;" version="1.1" viewbox="0 0 9.1750002 11.0375" width="9.1750002" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,11.0375)"> <g transform="translate(72,-63.17)"> <text transform="matrix(1,0,0,-1,-71.95,63.36)"> <tspan style="font-size: 12.50px; " x="0" y="0"> ℓ</t年代pan> </text> </g> </g> </svg>。两个长字符串互补(或一个完美的匹配)如果每个0在另一对应于一个1,相反。更普遍的是,一个<年代vg height="7.1374998" id="M13" style="vertical-align:-0.10033pt;width:11.225px;" version="1.1" viewbox="0 0 11.225 7.1374998" width="11.225" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,7.1375)"> <g transform="translate(72,-66.29)"> <text transform="matrix(1,0,0,-1,-71.95,66.44)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> </text> </g> </g> </svg>位匹配的定义是一对完全的地方<年代vg height="7.1374998" id="M14" style="vertical-align:-0.10033pt;width:11.225px;" version="1.1" viewbox="0 0 11.225 7.1374998" width="11.225" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,7.1375)"> <g transform="translate(72,-66.29)"> <text transform="matrix(1,0,0,-1,-71.95,66.44)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> </text> </g> </g> </svg>位相辅相成。因此,为了计算结合概率,我们首先定义函数<年代vg height="13.5625" id="M15" style="vertical-align:-2.21957pt;width:41.25px;" version="1.1" viewbox="0 0 41.25 13.5625" width="41.25" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,13.5625)"> <g transform="translate(72,-61.15)"> <text transform="matrix(1,0,0,-1,-71.95,63.41)"> <tspan style="font-size: 12.50px; " x="0" y="0"> ℎ</t年代pan> <tspan style="font-size: 12.50px; " x="7.214231" y="0"> (</t年代pan> <tspan style="font-size: 12.50px; " x="11.37773" y="0"> </t年代pan> <tspan style="font-size: 12.50px; " x="17.654236" y="0"> ,</t年代pan> <tspan style="font-size: 12.50px; " x="22.855484" y="0"> </t年代pan> <tspan style="font-size: 12.50px; " x="28.731894" y="0"> )</t年代pan> </text> </g> </g> </svg>给我们两个字符串之间的匹配的比特数<年代vg height="7.1750002" id="M16" style="vertical-align:-0.1254pt;width:7.9749999px;" version="1.1" viewbox="0 0 7.9749999 7.1750002" width="7.9749999" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,7.175)"> <g transform="translate(72,-66.26)"> <text transform="matrix(1,0,0,-1,-71.95,66.44)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> </text> </g> </g> </svg>和<年代vg height="10.7375" id="M17" style="vertical-align:-0.13794pt;width:7.4749999px;" version="1.1" viewbox="0 0 7.4749999 10.7375" width="7.4749999" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,10.7375)"> <g transform="translate(72,-63.41)"> <text transform="matrix(1,0,0,-1,-71.95,63.6)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> </text> </g> </g> </svg>(即。,the Hamming distance in the space of the bit-strings). Then, we define the function<年代vg height="13.45" id="M18" style="vertical-align:-2.21957pt;width:30.450001px;" version="1.1" viewbox="0 0 30.450001 13.45" width="30.450001" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,13.45)"> <g transform="translate(72,-61.24)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> <tspan style="font-size: 12.50px; " x="7.0391889" y="0"> (</t年代pan> <tspan style="font-size: 12.50px; " x="11.202688" y="0"> </t年代pan> <tspan style="font-size: 12.50px; " x="20.079819" y="0"> )</t年代pan> </text> </g> </g> </svg>的亲和力<年代vg height="7.1374998" id="M19" style="vertical-align:-0.10033pt;width:11.225px;" version="1.1" viewbox="0 0 11.225 7.1374998" width="11.225" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,7.1375)"> <g transform="translate(72,-66.29)"> <text transform="matrix(1,0,0,-1,-71.95,66.44)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> </text> </g> </g> </svg>一些比赛。以确保完美的比赛战胜不完美的,我们组<年代vg height="13.625" id="M20" style="vertical-align:-2.21957pt;width:28.4px;" version="1.1" viewbox="0 0 28.4 13.625" width="28.4" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,13.625)"> <g transform="translate(72,-61.1)"> <text transform="matrix(1,0,0,-1,-71.95,63.36)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> <tspan style="font-size: 12.50px; " x="7.0391889" y="0"> (</t年代pan> <tspan style="font-size: 12.50px; " x="11.202688" y="0"> ℓ</t年代pan> <tspan style="font-size: 12.50px; " x="18.441925" y="0"> )</t年代pan> </text> </g> </g> </svg>高价值和<年代vg height="13.45" id="M21" style="vertical-align:-2.21957pt;width:30.450001px;" version="1.1" viewbox="0 0 30.450001 13.45" width="30.450001" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,13.45)"> <g transform="translate(72,-61.24)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> <tspan style="font-size: 12.50px; " x="7.0391889" y="0"> (</t年代pan> <tspan style="font-size: 12.50px; " x="11.202688" y="0"> </t年代pan> <tspan style="font-size: 12.50px; " x="20.079819" y="0"> )</t年代pan> </text> </g> </g> </svg>(与<年代vg height="11.2375" id="M22" style="vertical-align:-0.30096pt;width:39.662498px;" version="1.1" viewbox="0 0 39.662498 11.2375" width="39.662498" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,11.2375)"> <g transform="translate(72,-63.01)"> <text transform="matrix(1,0,0,-1,-71.95,63.36)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> <tspan style="font-size: 12.50px; " x="12.340461" y="0"> <</t年代pan> <tspan style="font-size: 12.50px; " x="24.38085" y="0"> ℓ</t年代pan> </text> </g> </g> </svg>)降低值。指定的向量<年代vg height="7.1750002" id="M23" style="vertical-align:-0.1254pt;width:8.9375px;" version="1.1" viewbox="0 0 8.9375 7.1750002" width="8.9375" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,7.175)"> <g transform="translate(72,-66.26)"> <text transform="matrix(1,0,0,-1,-71.95,66.44)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> </text> </g> </g> </svg>,一个方法是直接指定它只需列出它的组件。另一种方法使用附加参数的参数<年代vg height="12.3" id="M24" style="vertical-align:-4.23843pt;width:11.225px;" version="1.1" viewbox="0 0 11.225 12.3" width="11.225" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,12.3)"> <g transform="translate(72,-62.16)"> <text transform="matrix(1,0,0,-1,-71.95,66.44)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> </text> <g> <path d="m -71.95,63.45 8.88,0" style="fill:none;stroke:#000000;stroke-width:0.82499999;stroke-linecap:butt;stroke-linejoin:miter;stroke-miterlimit:10;stroke-opacity:1;stroke-dasharray:none"></path> </g> </g> </g> </svg>,即允许最小匹配,<年代vg height="16" id="M25" style="vertical-align:-4.2635pt;width:57.674999px;" version="1.1" viewbox="0 0 57.674999 16" width="57.674999" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,16)"> <g transform="translate(72,-59.2)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> </text> <g> <path d="m -71.95,60.48 6.28,0" style="fill:none;stroke:#000000;stroke-width:0.82499999;stroke-linecap:butt;stroke-linejoin:miter;stroke-miterlimit:10;stroke-opacity:1;stroke-dasharray:none"></path> </g> <text transform="matrix(1,0,0,-1,-62.2,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> =</t年代pan> <tspan style="font-size: 12.50px; " x="12.027886" y="0"> </t年代pan> <tspan style="font-size: 12.50px; " x="19.079578" y="0"> (</t年代pan> <tspan style="font-size: 12.50px; " x="23.243076" y="0"> </t年代pan> </text> <g> <path d="m -38.95,60.51 8.88,0" style="fill:none;stroke:#000000;stroke-width:0.82499999;stroke-linecap:butt;stroke-linejoin:miter;stroke-miterlimit:10;stroke-opacity:1;stroke-dasharray:none"></path> </g> <text transform="matrix(1,0,0,-1,-30.07,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> )</t年代pan> </text> </g> </g> </svg>,最低级别的亲和力,和<年代vg height="14.5875" id="M26" style="vertical-align:-3.22282pt;width:14.15px;" version="1.1" viewbox="0 0 14.15 14.5875" width="14.15" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,14.5875)"> <g transform="translate(72,-60.33)"> <text transform="matrix(1,0,0,-1,-71.95,63.6)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> </text> <text transform="matrix(1,0,0,-1,-66.16,60.47)"> <tspan style="font-size: 8.75px; " x="0" y="0"> </t年代pan> </text> </g> </g> </svg>参数指定增加亲和力与一个更匹配,以以下方式计算:(i)使用参数<年代vg height="12.3" id="M27" style="vertical-align:-4.23843pt;width:11.225px;" version="1.1" viewbox="0 0 11.225 12.3" width="11.225" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,12.3)"> <g transform="translate(72,-62.16)"> <text transform="matrix(1,0,0,-1,-71.95,66.44)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> </text> <g> <path d="m -71.95,63.45 8.88,0" style="fill:none;stroke:#000000;stroke-width:0.82499999;stroke-linecap:butt;stroke-linejoin:miter;stroke-miterlimit:10;stroke-opacity:1;stroke-dasharray:none"></path> </g> </g> </g> </svg>,设置<年代vg height="16" id="M28" style="vertical-align:-4.2635pt;width:57.674999px;" version="1.1" viewbox="0 0 57.674999 16" width="57.674999" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,16)"> <g transform="translate(72,-59.2)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> <tspan style="font-size: 12.50px; " x="7.0391889" y="0"> (</t年代pan> <tspan style="font-size: 12.50px; " x="11.202688" y="0"> </t年代pan> </text> <g> <path d="m -60.73,60.51 8.87,0" style="fill:none;stroke:#000000;stroke-width:0.82499999;stroke-linecap:butt;stroke-linejoin:miter;stroke-miterlimit:10;stroke-opacity:1;stroke-dasharray:none"></path> </g> <text transform="matrix(1,0,0,-1,-51.86,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> )</t年代pan> <tspan style="font-size: 12.50px; " x="7.6268301" y="0"> =</t年代pan> <tspan style="font-size: 12.50px; " x="19.667219" y="0"> </t年代pan> </text> <g> <path d="m -32.18,60.48 6.27,0" style="fill:none;stroke:#000000;stroke-width:0.82499999;stroke-linecap:butt;stroke-linejoin:miter;stroke-miterlimit:10;stroke-opacity:1;stroke-dasharray:none"></path> </g> </g> </g> </svg>而对于<年代vg height="13.75" id="M29" style="vertical-align:-4.23843pt;width:41.700001px;" version="1.1" viewbox="0 0 41.700001 13.75" width="41.700001" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,13.75)"> <g transform="translate(72,-61)"> <text transform="matrix(1,0,0,-1,-71.95,65.27)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> <tspan style="font-size: 12.50px; " x="12.340461" y="0"> <</t年代pan> <tspan style="font-size: 12.50px; " x="24.38085" y="0"> </t年代pan> </text> <g> <path d="m -47.56,62.29 8.88,0" style="fill:none;stroke:#000000;stroke-width:0.82499999;stroke-linecap:butt;stroke-linejoin:miter;stroke-miterlimit:10;stroke-opacity:1;stroke-dasharray:none"></path> </g> </g> </g> </svg>集<年代vg height="13.45" id="M30" style="vertical-align:-2.21957pt;width:30.450001px;" version="1.1" viewbox="0 0 30.450001 13.45" width="30.450001" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,13.45)"> <g transform="translate(72,-61.24)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> <tspan style="font-size: 12.50px; " x="7.0391889" y="0"> (</t年代pan> <tspan style="font-size: 12.50px; " x="11.202688" y="0"> </t年代pan> <tspan style="font-size: 12.50px; " x="20.079819" y="0"> )</t年代pan> </text> </g> </g> </svg>0(这提供了一个水平低于绑定不能发生);(2)强度的增加匹配增加一点将克隆数的比值的倒数与匹配<年代vg height="11.325" id="M31" style="vertical-align:-0.51414pt;width:36.6875px;" version="1.1" viewbox="0 0 36.6875 11.325" width="36.6875" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,11.325)"> <g transform="translate(72,-62.94)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> <tspan style="font-size: 12.50px; " x="11.652796" y="0"> +</t年代pan> <tspan style="font-size: 12.50px; " x="22.993017" y="0"> 1</t年代pan> </text> </g> </g> </svg>和<年代vg height="7.1374998" id="M32" style="vertical-align:-0.10033pt;width:11.225px;" version="1.1" viewbox="0 0 11.225 7.1374998" width="11.225" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,7.1375)"> <g transform="translate(72,-66.29)"> <text transform="matrix(1,0,0,-1,-71.95,66.44)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> </text> </g> </g> </svg>乘以参数<年代vg height="14.5875" id="M33" style="vertical-align:-3.22282pt;width:14.15px;" version="1.1" viewbox="0 0 14.15 14.5875" width="14.15" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,14.5875)"> <g transform="translate(72,-60.33)"> <text transform="matrix(1,0,0,-1,-71.95,63.6)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> </text> <text transform="matrix(1,0,0,-1,-66.16,60.47)"> <tspan style="font-size: 8.75px; " x="0" y="0"> </t年代pan> </text> </g> </g> </svg>。在公式,<年代pan class="equation" id="eq1"> <svg height="45.787498" id="M34" preserveaspectratio="xMaxYMin" style="vertical-align:-0pt;width:700.9375px;" version="1.1" viewbox="0 0 700.9375 45.787498" width="700.9375" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,45.7875)"> <g transform="translate(72,-35.37)"> <text transform="matrix(1,0,0,-1,157.85,58.78)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> <tspan style="font-size: 12.50px; " x="9.1271896" y="0"> (</t年代pan> <tspan style="font-size: 12.50px; " x="13.290689" y="0"> </t年代pan> <tspan style="font-size: 12.50px; " x="24.955988" y="0"> +</t年代pan> <tspan style="font-size: 12.50px; " x="36.296207" y="0"> 1</t年代pan> <tspan style="font-size: 12.50px; " x="42.54771" y="0"> )</t年代pan> </text> <g> <path d="m 157.85,53.68 46.71,0" style="fill:none;stroke:#000000;stroke-width:0.82499999;stroke-linecap:butt;stroke-linejoin:miter;stroke-miterlimit:10;stroke-opacity:1;stroke-dasharray:none"></path> </g> <text transform="matrix(1,0,0,-1,168.04,41.81)"> <tspan style="font-size: 12.50px; " x="41.189999" y="-8.75"> =</t年代pan> <tspan style="font-size: 12.50px; " x="54.43" y="-19.32"> </t年代pan> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> <tspan style="font-size: 12.50px; " x="9.1271896" y="0"> (</t年代pan> <tspan style="font-size: 12.50px; " x="13.290689" y="0"> </t年代pan> <tspan style="font-size: 12.50px; " x="22.167818" y="0"> )</t年代pan> </text> <text transform="matrix(1,0,0,-1,228.26,58.01)"> <tspan style="font-size: 8.75px; " x="0" y="0"> </t年代pan> </text> <text transform="matrix(1,0,0,-1,235.77,58.62)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> </text> <text transform="matrix(1,0,0,-1,244.28,64.78)"> <tspan style="font-size: 8.75px; " x="0" y="0"> ℓ</t年代pan> <tspan style="font-size: 8.75px; " x="-0.56999999" y="6.98"> </t年代pan> </text> <text transform="matrix(1,0,0,-1,252.01,58.62)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> </text> <g> <path d="m 222.47,53.68 35.39,0" style="fill:none;stroke:#000000;stroke-width:0.82499999;stroke-linecap:butt;stroke-linejoin:miter;stroke-miterlimit:10;stroke-opacity:1;stroke-dasharray:none"></path> </g> <text transform="matrix(1,0,0,-1,223.93,37.47)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> </text> <text transform="matrix(1,0,0,-1,237.63,44.16)"> <tspan style="font-size: 8.75px; " x="0" y="0"> ℓ</t年代pan> <tspan style="font-size: 8.75px; " x="-5.7600002" y="7.7600002"> </t年代pan> <tspan style="font-size: 8.75px; " x="0.45392001" y="7.7600002"> +</t年代pan> <tspan style="font-size: 8.75px; " x="6.4490399" y="7.7600002"> 1</t年代pan> </text> <text transform="matrix(1,0,0,-1,250.54,37.47)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> <tspan style="font-size: 12.50px; " x="8.5100002" y="-13.09"> 。</t年代pan> <tspan style="font-size: 12.50px; " x="223.58" y="-13.09"> (</t年代pan> <tspan style="font-size: 12.50px; " x="227.7435" y="-13.09"> 1</t年代pan> <tspan style="font-size: 12.50px; " x="233.995" y="-13.09"> )</t年代pan> </text> </g> </g> </svg></span>这允许设置的低端价值<年代vg height="13.45" id="M35" style="vertical-align:-2.21957pt;width:30.450001px;" version="1.1" viewbox="0 0 30.450001 13.45" width="30.450001" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,13.45)"> <g transform="translate(72,-61.24)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> <tspan style="font-size: 12.50px; " x="7.0391889" y="0"> (</t年代pan> <tspan style="font-size: 12.50px; " x="11.202688" y="0"> </t年代pan> <tspan style="font-size: 12.50px; " x="20.079819" y="0"> )</t年代pan> </text> </g> </g> </svg>和陡度的增加匹配碎片的数量递增。它通常比提供更方便<年代vg height="7.1750002" id="M36" style="vertical-align:-0.1254pt;width:8.9375px;" version="1.1" viewbox="0 0 8.9375 7.1750002" width="8.9375" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,7.175)"> <g transform="translate(72,-66.26)"> <text transform="matrix(1,0,0,-1,-71.95,66.44)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> </text> </g> </g> </svg>向量直接。一般来说,建议设置<年代vg height="12.3" id="M37" style="vertical-align:-4.23843pt;width:11.225px;" version="1.1" viewbox="0 0 11.225 12.3" width="11.225" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,12.3)"> <g transform="translate(72,-62.16)"> <text transform="matrix(1,0,0,-1,-71.95,66.44)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> </text> <g> <path d="m -71.95,63.45 8.88,0" style="fill:none;stroke:#000000;stroke-width:0.82499999;stroke-linecap:butt;stroke-linejoin:miter;stroke-miterlimit:10;stroke-opacity:1;stroke-dasharray:none"></path> </g> </g> </g> </svg>有点接近<年代vg height="11.0375" id="M38" style="vertical-align:-0.13794pt;width:9.1750002px;" version="1.1" viewbox="0 0 9.1750002 11.0375" width="9.1750002" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,11.0375)"> <g transform="translate(72,-63.17)"> <text transform="matrix(1,0,0,-1,-71.95,63.36)"> <tspan style="font-size: 12.50px; " x="0" y="0"> ℓ</t年代pan> </text> </g> </g> </svg>位为了限制允许的范围匹配几位,所以抗体的数量在给定的抗原反应仍是可控的。</gydF4y2Bap> <div class="partial-carousel-wrapper"> <div class="floats-partial-section"> <div class="floats-partial-content"> <div class="partial-carousel--full-image partial-carousel-2953a7cf3e52d14a771df2b95d2b5c13"> <div class="partial-carousel--single-image"> <img loading="lazy" alt="" src="https://static.hindawi.com/articles/cmmm/volume-2012/842329/figures/842329.fig.001.jpg"> <br> <strong></strong> </div> </div> </div> <div class="floats-partial-middle"> <div class="floats-partial-middle--thumbs"> <div class="partial-carousel-dots-2953a7cf3e52d14a771df2b95d2b5c13 partial-carousel-thumbnail"> <button aria-label="Slide to " class="partial-carousel-dot"><img loading="lazy" alt="" src="https://static.hindawi.com/articles/cmmm/volume-2012/842329/thumbnails/842329.fig.001_th.jpg"><br><strong></strong></button> </div> </div> <div class="floats-partial-middle--nav"> <div class="partial-carousel-next-prev-2953a7cf3e52d14a771df2b95d2b5c13 partial-carousel-next-prev"> <button aria-label="Previous" class="carousel-prev"></button> <button aria-label="Next" class="carousel-next"></button> </div> </div> </div> <div class="floats-partial-footer"> <div class="floats-partial-caption"> <span class="caption-text">图1</年代pan> <a aria-label="View full page" class="caption-partial-url" href="//www.newsama.com/journals/cmmm/2012/842329/fig1/" title="" target="_blank"></a> </div> <div class="floats-partial-caption-text"> <table> <tbody> <tr> <td>分子亲和力计算基于汉明距离的二进制字符串代表结合位点的实体进行交互。图中T淋巴细胞受体结合的MHC-peptide复杂抗原呈递细胞。</tgydF4y2Bad> </tr> </tbody> </table> </div> </div> </div> </div> <p>与许多免疫模型不同的是,现在不仅模拟了细胞水平细胞间的相互作用也是胞内抗原的过程中,吸收和表示。胞质和内吞作用的通路建模。在模型中,内源性抗原是分散,结合MHC类我为介绍分子ctl的细胞表面受体,而外源性抗原是退化成更小的部分(即。肽),然后绑定到MHC II级分子这个受体(表表示的<一个href="//www.newsama.com/journals/cmmm/2012/842329/tab1/" target="_blank">1</一个>)。MHC分子之间的亲和力和抗原肽以稍微不同的方式计算比细胞受体和抗原决定之间。首先,计算半数以上位串匹配;其次,没有最小匹配。两个一半字符串之间的关联值的匹配<年代vg height="7.1374998" id="M39" style="vertical-align:-0.10033pt;width:11.225px;" version="1.1" viewbox="0 0 11.225 7.1374998" width="11.225" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,7.1375)"> <g transform="translate(72,-66.29)"> <text transform="matrix(1,0,0,-1,-71.95,66.44)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> </text> </g> </g> </svg>,<年代vg height="13.0625" id="M40" style="vertical-align:-1.76814pt;width:134.66251px;" version="1.1" viewbox="0 0 134.66251 13.0625" width="134.66251" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,13.0625)"> <g transform="translate(72,-61.55)"> <text transform="matrix(1,0,0,-1,-71.95,63.36)"> <tspan style="font-size: 12.50px; " x="0" y="0"> f</t年代pan> <tspan style="font-size: 12.50px; " x="3.7634029" y="0"> o</t年代pan> <tspan style="font-size: 12.50px; " x="10.014903" y="0"> r</t年代pan> <tspan style="font-size: 12.50px; " x="18.341902" y="0"> 一个</t年代pan> <tspan style="font-size: 12.50px; " x="23.893232" y="0"> l</t年代pan> <tspan style="font-size: 12.50px; " x="27.369066" y="0"> l</t年代pan> <tspan style="font-size: 12.50px; " x="35.0084" y="0"> </t年代pan> <tspan style="font-size: 12.50px; " x="47.361362" y="0"> =</t年代pan> <tspan style="font-size: 12.50px; " x="59.401752" y="0"> 0</t年代pan> <tspan style="font-size: 12.50px; " x="65.653252" y="0"> ,</t年代pan> <tspan style="font-size: 12.50px; " x="70.8545" y="0"> …</t年代pan> <tspan style="font-size: 12.50px; " x="85.445503" y="0"> ,</t年代pan> <tspan style="font-size: 12.50px; " x="90.659256" y="0"> ℓ</t年代pan> <tspan style="font-size: 12.50px; " x="97.898491" y="0"> /</t年代pan> <tspan style="font-size: 12.50px; " x="101.37432" y="0"> 2</t年代pan> </text> </g> </g> </svg>,被定义为<年代pan class="equation" id="eq2"> <svg height="34.112499" id="M41" preserveaspectratio="xMaxYMin" style="vertical-align:-0pt;width:700.9375px;" version="1.1" viewbox="0 0 700.9375 34.112499" width="700.9375" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,34.1125)"> <g transform="translate(72,-44.71)"> <text transform="matrix(1,0,0,-1,162.87,53.52)"> <tspan style="font-size: 12.50px; " x="41.779999" y="4.9200001"> </t年代pan> <tspan style="font-size: 12.50px; " x="50.34" y="-7.25"> 1</t年代pan> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> <tspan style="font-size: 12.50px; " x="9.0521717" y="0"> (</t年代pan> <tspan style="font-size: 12.50px; " x="13.215671" y="0"> </t年代pan> <tspan style="font-size: 12.50px; " x="22.0928" y="0"> )</t年代pan> <tspan style="font-size: 12.50px; " x="29.732134" y="0"> =</t年代pan> </text> <g> <path d="m 213.21,56.64 6.25,0" style="fill:none;stroke:#000000;stroke-width:0.82499999;stroke-linecap:butt;stroke-linejoin:miter;stroke-miterlimit:10;stroke-opacity:1;stroke-dasharray:none"></path> </g> <text transform="matrix(1,0,0,-1,213.21,44.76)"> <tspan style="font-size: 12.50px; " x="0" y="0"> 2</t年代pan> <tspan style="font-size: 12.50px; " x="7.4400001" y="-3.8399999"> </t年代pan> </text> <text transform="matrix(1,0,0,-1,228.25,65.94)"> <tspan style="font-size: 8.75px; " x="0" y="0"> ℓ</t年代pan> <tspan style="font-size: 8.75px; " x="5.0674081" y="0"> /</t年代pan> <tspan style="font-size: 8.75px; " x="7.500464" y="0"> 2</t年代pan> <tspan style="font-size: 8.75px; " x="11.876464" y="0"> −</t年代pan> <tspan style="font-size: 8.75px; " x="17.871584" y="0"> </t年代pan> </text> <text transform="matrix(1,0,0,-1,252.84,53.52)"> <tspan style="font-size: 12.50px; " x="0" y="0"> 。</t年代pan> <tspan style="font-size: 12.50px; " x="221.28" y="-1.71"> (</t年代pan> <tspan style="font-size: 12.50px; " x="225.4435" y="-1.71"> 2</t年代pan> <tspan style="font-size: 12.50px; " x="231.69499" y="-1.71"> )</t年代pan> </text> </g> </g> </svg></span>这个函数<年代vg height="13.55" id="M42" style="vertical-align:-2.29482pt;width:30.35px;" version="1.1" viewbox="0 0 30.35 13.55" width="30.35" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,13.55)"> <g transform="translate(72,-61.16)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> <tspan style="font-size: 12.50px; " x="6.9641709" y="0"> (</t年代pan> <tspan style="font-size: 12.50px; " x="11.12767" y="0"> </t年代pan> <tspan style="font-size: 12.50px; " x="20.004801" y="0"> )</t年代pan> </text> </g> </g> </svg>代表的概率匹配的肽<年代vg height="7.1374998" id="M43" style="vertical-align:-0.10033pt;width:11.225px;" version="1.1" viewbox="0 0 11.225 7.1374998" width="11.225" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,7.1375)"> <g transform="translate(72,-66.29)"> <text transform="matrix(1,0,0,-1,-71.95,66.44)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> </text> </g> </g> </svg>MHC分子的结合,提出了与后续的细胞表面细胞识别。</gydF4y2Bap> <p>而像细胞分别代表(即宏观实体。,they are considered as agents), low-molecular, weight molecules, such as interleukins or chemokines, are represented in terms of their concentration. The corresponding dynamics is modeled by the following parabolic partial differential equation that describes a uniform diffusion process with the addition of a degradation term that takes into account the finite half-life of molecules:<年代pan class="equation" id="eq3"> <svg height="30.737499" id="M44" preserveaspectratio="xMaxYMin" style="vertical-align:-0pt;width:700.9375px;" version="1.1" viewbox="0 0 700.9375 30.737499" width="700.9375" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,30.7375)"> <g transform="translate(72,-47.41)"> <text transform="matrix(1,0,0,-1,142.27,63.6)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> <tspan style="font-size: 12.50px; " x="6.3765302" y="0"> </t年代pan> </text> <g> <path d="m 142.27,59.47 12.2,0" style="fill:none;stroke:#000000;stroke-width:0.82499999;stroke-linecap:butt;stroke-linejoin:miter;stroke-miterlimit:10;stroke-opacity:1;stroke-dasharray:none"></path> </g> <text transform="matrix(1,0,0,-1,143.22,47.59)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> <tspan style="font-size: 12.50px; " x="6.3765302" y="0"> </t年代pan> <tspan style="font-size: 12.50px; " x="15.92" y="-8.7600002"> =</t年代pan> <tspan style="font-size: 12.50px; " x="27.947886" y="-8.7600002"> </t年代pan> <tspan style="font-size: 12.50px; " x="38.012802" y="-8.7600002"> ∇</t年代pan> </text> <text transform="matrix(1,0,0,-1,190.38,61.35)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 2</t年代pan> </text> <text transform="matrix(1,0,0,-1,195.26,56.35)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> <tspan style="font-size: 12.50px; " x="7.9519081" y="0"> −</t年代pan> <tspan style="font-size: 12.50px; " x="19.304632" y="0"> </t年代pan> <tspan style="font-size: 12.50px; " x="26.068754" y="0"> </t年代pan> <tspan style="font-size: 12.50px; " x="34.033165" y="0"> +</t年代pan> <tspan style="font-size: 12.50px; " x="45.373386" y="0"> </t年代pan> <tspan style="font-size: 12.50px; " x="52.962708" y="0"> (</t年代pan> <tspan style="font-size: 12.50px; " x="57.126205" y="0"> </t年代pan> <tspan style="font-size: 12.50px; " x="64.002853" y="0"> ,</t年代pan> <tspan style="font-size: 12.50px; " x="69.204102" y="0"> </t年代pan> <tspan style="font-size: 12.50px; " x="73.117546" y="0"> )</t年代pan> <tspan style="font-size: 12.50px; " x="79.369041" y="0"> ,</t年代pan> <tspan style="font-size: 12.50px; " x="278.85999" y="-0.23"> (</t年代pan> <tspan style="font-size: 12.50px; " x="283.0235" y="-0.23"> 3</t年代pan> <tspan style="font-size: 12.50px; " x="289.27499" y="-0.23"> )</t年代pan> </text> </g> </g> </svg></span>在哪里<年代vg height="13.45" id="M45" style="vertical-align:-2.21957pt;width:62.887501px;" version="1.1" viewbox="0 0 62.887501 13.45" width="62.887501" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,13.45)"> <g transform="translate(72,-61.24)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> <tspan style="font-size: 12.50px; " x="8.6520758" y="0"> =</t年代pan> <tspan style="font-size: 12.50px; " x="20.692465" y="0"> </t年代pan> <tspan style="font-size: 12.50px; " x="25.88121" y="0"> (</t年代pan> <tspan style="font-size: 12.50px; " x="30.044708" y="0"> </t年代pan> <tspan style="font-size: 12.50px; " x="36.92136" y="0"> ,</t年代pan> <tspan style="font-size: 12.50px; " x="42.135109" y="0"> </t年代pan> <tspan style="font-size: 12.50px; " x="46.04855" y="0"> )</t年代pan> </text> </g> </g> </svg>趋化因子的浓度,<年代vg height="13.45" id="M46" style="vertical-align:-2.21957pt;width:37.412498px;" version="1.1" viewbox="0 0 37.412498 13.45" width="37.412498" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,13.45)"> <g transform="translate(72,-61.24)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> <tspan style="font-size: 12.50px; " x="5.5013199" y="0"> (</t年代pan> <tspan style="font-size: 12.50px; " x="9.6648188" y="0"> </t年代pan> <tspan style="font-size: 12.50px; " x="16.54147" y="0"> ,</t年代pan> <tspan style="font-size: 12.50px; " x="21.742718" y="0"> </t年代pan> <tspan style="font-size: 12.50px; " x="25.656157" y="0"> )</t年代pan> </text> </g> </g> </svg>源项,<年代vg height="10.325" id="M47" style="vertical-align:-0.0pt;width:12.7px;" version="1.1" viewbox="0 0 12.7 10.325" width="12.7" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,10.325)"> <g transform="translate(72,-63.74)"> <text transform="matrix(1,0,0,-1,-71.95,63.79)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> </text> </g> </g> </svg>是扩散系数,<年代vg height="11.05" id="M48" style="vertical-align:-0.20064pt;width:68.099998px;" version="1.1" viewbox="0 0 68.099998 11.05" width="68.099998" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,11.05)"> <g transform="translate(72,-63.16)"> <text transform="matrix(1,0,0,-1,-71.95,63.41)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> <tspan style="font-size: 12.50px; " x="10.227454" y="0"> =</t年代pan> <tspan style="font-size: 12.50px; " x="22.267843" y="0"> l</t年代pan> <tspan style="font-size: 12.50px; " x="25.743677" y="0"> n</t年代pan> <tspan style="font-size: 12.50px; " x="38.246677" y="0"> 2</t年代pan> <tspan style="font-size: 12.50px; " x="44.498177" y="0"> /</t年代pan> <tspan style="font-size: 12.50px; " x="47.97401" y="0"> </t年代pan> </text> </g> </g> </svg>在哪里<年代vg height="6.8874998" id="M49" style="vertical-align:-0.0627pt;width:8.125px;" version="1.1" viewbox="0 0 8.125 6.8874998" width="8.125" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,6.8875)"> <g transform="translate(72,-66.49)"> <text transform="matrix(1,0,0,-1,-71.95,66.6)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> </text> </g> </g> </svg>半衰期。我们假设<年代vg height="16.637501" id="M50" style="vertical-align:-2.29482pt;width:93.487503px;" version="1.1" viewbox="0 0 93.487503 16.637501" width="93.487503" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,16.6375)"> <g transform="translate(72,-58.69)"> <text transform="matrix(1,0,0,-1,-71.95,61.03)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> <tspan style="font-size: 12.50px; " x="13.340701" y="0"> =</t年代pan> <tspan style="font-size: 12.50px; " x="25.38109" y="0"> 3</t年代pan> <tspan style="font-size: 12.50px; " x="31.632589" y="0"> 0</t年代pan> <tspan style="font-size: 12.50px; " x="37.88409" y="0"> 0</t年代pan> <tspan style="font-size: 12.50px; " x="44.13559" y="0"> 0</t年代pan> <tspan style="font-size: 12.50px; " x="52.47509" y="0"> </t年代pan> <tspan style="font-size: 12.50px; " x="60.089417" y="0"> 米</t年代pan> </text> <text transform="matrix(1,0,0,-1,-2.13,66.03)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 2</t年代pan> </text> </g> </g> </svg>/分钟,<年代vg height="10.9125" id="M51" style="vertical-align:-0.17555pt;width:37.9375px;" version="1.1" viewbox="0 0 37.9375 10.9125" width="37.9375" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,10.9125)"> <g transform="translate(72,-63.27)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> <tspan style="font-size: 12.50px; " x="9.8648672" y="0"> =</t年代pan> <tspan style="font-size: 12.50px; " x="21.905256" y="0"> 3</t年代pan> </text> </g> </g> </svg>小时的趋化因子(<一个href="#B31">31日</一个>,<一个href="#B32">32</一个>]。不同的细胞迁移也考虑在内。TH细胞平均速度最快的11<年代vg height="10.175" id="M52" style="vertical-align:-2.29482pt;width:21.799999px;" version="1.1" viewbox="0 0 21.799999 10.175" width="21.799999" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,10.175)"> <g transform="translate(72,-63.86)"> <text transform="matrix(1,0,0,-1,-71.95,66.2)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> <tspan style="font-size: 12.50px; " x="7.6018238" y="0"> 米</t年代pan> </text> </g> </g> </svg>/分钟,其次是与6 B细胞<年代vg height="10.175" id="M53" style="vertical-align:-2.29482pt;width:21.799999px;" version="1.1" viewbox="0 0 21.799999 10.175" width="21.799999" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,10.175)"> <g transform="translate(72,-63.86)"> <text transform="matrix(1,0,0,-1,-71.95,66.2)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> <tspan style="font-size: 12.50px; " x="7.6018238" y="0"> 米</t年代pan> </text> </g> </g> </svg>/分钟和直流速度3<年代vg height="10.175" id="M54" style="vertical-align:-2.29482pt;width:21.799999px;" version="1.1" viewbox="0 0 21.799999 10.175" width="21.799999" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,10.175)"> <g transform="translate(72,-63.86)"> <text transform="matrix(1,0,0,-1,-71.95,66.2)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> <tspan style="font-size: 12.50px; " x="7.6018238" y="0"> 米</t年代pan> </text> </g> </g> </svg>/分钟(<一个href="#B32">32</一个>]。</gydF4y2Bap> <p>表中列出的规则<一个href="//www.newsama.com/journals/cmmm/2012/842329/tab1/" target="_blank">1</一个>为每个时间步执行。的随机执行这些规则,如蒙特卡罗方法,产生一个逻辑因果/影响序列的事件免疫应答和免疫记忆的发展。这一系列事件的起点是注射抗原(启动)。</gydF4y2Bap> <p>系统旨在维护全球人口的稳定状态下的细胞(<gydF4y2Bai>体内平衡</gydF4y2Bai>)如果没有感染。这是通过建模生/死过程均值回归过程的类型:<年代pan class="equation" id="eq4"> <svg height="37.237499" id="M55" preserveaspectratio="xMaxYMin" style="vertical-align:-0pt;width:700.9375px;" version="1.1" viewbox="0 0 700.9375 37.237499" width="700.9375" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,37.2375)"> <g transform="translate(72,-42.21)"> <text transform="matrix(1,0,0,-1,114.46,63.47)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> <tspan style="font-size: 12.50px; " x="6.6515961" y="0"> </t年代pan> </text> <text transform="matrix(1,0,0,-1,127.99,60.34)"> <tspan style="font-size: 8.75px; " x="0" y="0"> </t年代pan> </text> <text transform="matrix(1,0,0,-1,133.29,63.48)"> <tspan style="font-size: 12.50px; " x="0" y="0"> (</t年代pan> <tspan style="font-size: 12.50px; " x="4.1700001" y="0.0099999998"> </t年代pan> <tspan style="font-size: 12.50px; " x="8.0834389" y="0.0099999998"> )</t年代pan> </text> <g> <path d="m 114.46,57.36 31.07,0" style="fill:none;stroke:#000000;stroke-width:0.82499999;stroke-linecap:butt;stroke-linejoin:miter;stroke-miterlimit:10;stroke-opacity:1;stroke-dasharray:none"></path> </g> <text transform="matrix(1,0,0,-1,124.72,45.48)"> <tspan style="font-size: 12.50px; " x="25.48" y="-8.75"> =</t年代pan> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> <tspan style="font-size: 12.50px; " x="6.6515961" y="0"> </t年代pan> <tspan style="font-size: 12.50px; " x="38.720001" y="-17.93"> l</t年代pan> <tspan style="font-size: 12.50px; " x="42.195835" y="-17.93"> o</t年代pan> <tspan style="font-size: 12.50px; " x="48.447334" y="-17.93"> g</t年代pan> </text> <text transform="matrix(1,0,0,-1,179.42,60.25)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 2</t年代pan> </text> <g> <path d="m 163.44,57.36 20.85,0" style="fill:none;stroke:#000000;stroke-width:0.82499999;stroke-linecap:butt;stroke-linejoin:miter;stroke-miterlimit:10;stroke-opacity:1;stroke-dasharray:none"></path> </g> <text transform="matrix(1,0,0,-1,169.49,45.48)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> </text> <text transform="matrix(1,0,0,-1,175.02,42.36)"> <tspan style="font-size: 8.75px; " x="0" y="0"> </t年代pan> </text> <text transform="matrix(1,0,0,-1,187.57,51.72)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> <tspan style="font-size: 12.50px; " x="5.8499999" y="-2.51"> </t年代pan> </text> <text transform="matrix(1,0,0,-1,200.3,51.11)"> <tspan style="font-size: 8.75px; " x="0" y="0"> </t年代pan> </text> <text transform="matrix(1,0,0,-1,205.6,54.24)"> <tspan style="font-size: 12.50px; " x="0" y="0"> (</t年代pan> <tspan style="font-size: 12.50px; " x="4.1634989" y="0"> 0</t年代pan> <tspan style="font-size: 12.50px; " x="10.414999" y="0"> )</t年代pan> <tspan style="font-size: 12.50px; " x="17.354164" y="0"> −</t年代pan> <tspan style="font-size: 12.50px; " x="28.694386" y="0"> </t年代pan> </text> <text transform="matrix(1,0,0,-1,241.18,51.11)"> <tspan style="font-size: 8.75px; " x="0" y="0"> </t年代pan> </text> <text transform="matrix(1,0,0,-1,246.48,54.24)"> <tspan style="font-size: 12.50px; " x="12.24" y="2.52"> </t年代pan> <tspan style="font-size: 12.50px; " x="0" y="0"> (</t年代pan> <tspan style="font-size: 12.50px; " x="4.1634989" y="0"> </t年代pan> <tspan style="font-size: 12.50px; " x="8.0769377" y="0"> )</t年代pan> <tspan style="font-size: 12.50px; " x="20.870001" y="0.0099999998"> +</t年代pan> <tspan style="font-size: 12.50px; " x="32.21022" y="0.0099999998"> </t年代pan> <tspan style="font-size: 12.50px; " x="41.637482" y="0.0099999998"> (</t年代pan> <tspan style="font-size: 12.50px; " x="45.800983" y="0.0099999998"> </t年代pan> <tspan style="font-size: 12.50px; " x="49.71442" y="0.0099999998"> )</t年代pan> <tspan style="font-size: 12.50px; " x="55.953419" y="0.0099999998"> ,</t年代pan> <tspan style="font-size: 12.50px; " x="227.64" y="0.25999999"> (</t年代pan> <tspan style="font-size: 12.50px; " x="231.8035" y="0.25999999"> 4</t年代pan> <tspan style="font-size: 12.50px; " x="238.05499" y="0.25999999"> )</t年代pan> </text> </g> </g> </svg></span>在哪里<年代vg height="14.7125" id="M56" style="vertical-align:-3.2316pt;width:28.049999px;" version="1.1" viewbox="0 0 28.049999 14.7125" width="28.049999" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,14.7125)"> <g transform="translate(72,-60.23)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> </text> <text transform="matrix(1,0,0,-1,-65.07,60.37)"> <tspan style="font-size: 8.75px; " x="0" y="0"> </t年代pan> </text> <text transform="matrix(1,0,0,-1,-61.85,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> (</t年代pan> <tspan style="font-size: 12.50px; " x="4.1634989" y="0"> </t年代pan> <tspan style="font-size: 12.50px; " x="8.0769377" y="0"> )</t年代pan> </text> </g> </g> </svg>是人口<年代vg height="9.9250002" id="M57" style="vertical-align:-0.13794pt;width:4.9875002px;" version="1.1" viewbox="0 0 4.9875002 9.9250002" width="4.9875002" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,9.925)"> <g transform="translate(72,-64.06)"> <text transform="matrix(1,0,0,-1,-71.95,64.25)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> </text> </g> </g> </svg>在时间<年代vg height="9.9250002" id="M58" style="vertical-align:-0.13794pt;width:4.9875002px;" version="1.1" viewbox="0 0 4.9875002 9.9250002" width="4.9875002" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,9.925)"> <g transform="translate(72,-64.06)"> <text transform="matrix(1,0,0,-1,-71.95,64.25)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> </text> </g> </g> </svg>,<年代vg height="10.8375" id="M59" style="vertical-align:-3.2316pt;width:11.0625px;" version="1.1" viewbox="0 0 11.0625 10.8375" width="11.0625" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,10.8375)"> <g transform="translate(72,-63.33)"> <text transform="matrix(1,0,0,-1,-71.95,66.6)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> </text> <text transform="matrix(1,0,0,-1,-66.42,63.47)"> <tspan style="font-size: 8.75px; " x="0" y="0"> </t年代pan> </text> </g> </g> </svg>是特定的半衰期参数,<年代vg height="13.45" id="M60" style="vertical-align:-2.21957pt;width:24.6px;" version="1.1" viewbox="0 0 24.6 13.45" width="24.6" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,13.45)"> <g transform="translate(72,-61.24)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> <tspan style="font-size: 12.50px; " x="7.3267579" y="0"> (</t年代pan> <tspan style="font-size: 12.50px; " x="11.490257" y="0"> </t年代pan> <tspan style="font-size: 12.50px; " x="15.403696" y="0"> )</t年代pan> </text> </g> </g> </svg>是一个高斯随机噪声。</gydF4y2Bap> <p>最初的系统是天真的没有<年代vg height="10.325" id="M61" style="vertical-align:-0.0pt;width:11.225px;" version="1.1" viewbox="0 0 11.225 10.325" width="11.225" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,10.325)"> <g transform="translate(72,-63.74)"> <text transform="matrix(1,0,0,-1,-71.95,63.79)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> </text> </g> </g> </svg>和<年代vg height="10.325" id="M62" style="vertical-align:-0.0pt;width:11.625px;" version="1.1" viewbox="0 0 11.625 10.325" width="11.625" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,10.325)"> <g transform="translate(72,-63.74)"> <text transform="matrix(1,0,0,-1,-71.95,63.79)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> </text> </g> </g> </svg>记忆细胞和浆细胞和抗体。模拟的各个步骤的免疫反应取决于实际上是注射,例如,重组病毒或细菌。</gydF4y2Bap> <p>模型包含许多参数的值已经确定如下。这些参数可以分为三类:(i)未知的值或自由参数,后设置一个调优过程始于一个初始迭代评估他们的价值观和提高模拟结果的小修改参数;(2)参数对应于系统的初始条件,确定问题接受调查;(3)参数的值是众所周知的,可以从免疫学文学。</gydF4y2Bap> <p>给定初始条件由模拟量确定细胞填充空间的数量根据已知白细胞公式,模型运行在体内平衡的亚稳状态确定。在缺乏抗原刺激,周围的人群的免疫细胞随机波动平均值。在一个抗原挑战由注入一定量的病原体,系统远离亚稳状态识别侮辱分子和免疫反应可能或不包括山体液和细胞毒性的部署炮兵。一旦抗原被清除,系统回到前一个平衡状态是不一样的,因为它包含一个转变系统特异性免疫记忆。此内存允许更快和更强的反应以后遇到相同(或相似)的病原体。</gydF4y2Bap> <p>图<一个href="//www.newsama.com/journals/cmmm/2012/842329/fig2/" target="_blank">2</一个>显示了该动力学作为一个典型的例子免疫实验包括在注射一天零,大约十周后通用疫苗免疫原性的物质。启动的结果是抗原清除在大约四天(爆发)抗体引起峰值在第二和第三周(左下侧板)。不同的特异性(即。,binary strings) of the antibodies elicited are shown in the same figure. The figure also shows the corresponding antibody-producing plasma cells (bottom-right panel) and the immunocomplexes titer (up-right panel) consisting of antigen clotted with antibodies.</p> <div class="partial-carousel-wrapper"> <div class="floats-partial-section"> <div class="floats-partial-content"> <div class="partial-carousel--full-image partial-carousel-ade25a322a8e5ff5f6193d4d07a055bd"> <div class="partial-carousel--single-image"> <img loading="lazy" alt="(一)gydF4y2Ba" src="https://static.hindawi.com/articles/cmmm/volume-2012/842329/figures/842329.fig.002a.jpg"> <br> <strong>(一)</年代trong> </div> <div class="partial-carousel--single-image"> <img loading="lazy" alt="(b)gydF4y2Ba" src="https://static.hindawi.com/articles/cmmm/volume-2012/842329/figures/842329.fig.002b.jpg"> <br> <strong>(b)</年代trong> </div> <div class="partial-carousel--single-image"> <img loading="lazy" alt="(c)gydF4y2Ba" src="https://static.hindawi.com/articles/cmmm/volume-2012/842329/figures/842329.fig.002c.jpg"> <br> <strong>(c)</年代trong> </div> <div class="partial-carousel--single-image"> <img loading="lazy" alt="(d)gydF4y2Ba" src="https://static.hindawi.com/articles/cmmm/volume-2012/842329/figures/842329.fig.002d.jpg"> <br> <strong>(d)</年代trong> </div> </div> </div> <div class="floats-partial-middle"> <div class="floats-partial-middle--thumbs"> <div class="partial-carousel-dots-ade25a322a8e5ff5f6193d4d07a055bd partial-carousel-thumbnail"> <button aria-label="Slide to (a) " class="partial-carousel-dot"><img loading="lazy" alt="(一)gydF4y2Ba" src="https://static.hindawi.com/articles/cmmm/volume-2012/842329/thumbnails/842329.fig.002a_th.jpg"><br><strong>(一)</年代trong></button> <button aria-label="Slide to (b) " class="partial-carousel-dot"><img loading="lazy" alt="(b)gydF4y2Ba" src="https://static.hindawi.com/articles/cmmm/volume-2012/842329/thumbnails/842329.fig.002b_th.jpg"><br><strong>(b)</年代trong></button> <button aria-label="Slide to (c) " class="partial-carousel-dot"><img loading="lazy" alt="(c)gydF4y2Ba" src="https://static.hindawi.com/articles/cmmm/volume-2012/842329/thumbnails/842329.fig.002c_th.jpg"><br><strong>(c)</年代trong></button> <button aria-label="Slide to (d) " class="partial-carousel-dot"><img loading="lazy" alt="(d)gydF4y2Ba" src="https://static.hindawi.com/articles/cmmm/volume-2012/842329/thumbnails/842329.fig.002d_th.jpg"><br><strong>(d)</年代trong></button> </div> </div> <div class="floats-partial-middle--nav"> <div class="partial-carousel-next-prev-ade25a322a8e5ff5f6193d4d07a055bd partial-carousel-next-prev"> <button aria-label="Previous" class="carousel-prev"></button> <button aria-label="Next" class="carousel-next"></button> </div> </div> </div> <div class="floats-partial-footer"> <div class="floats-partial-caption"> <span class="caption-text">图2</年代pan> <a aria-label="View full page" class="caption-partial-url" href="//www.newsama.com/journals/cmmm/2012/842329/fig2/" title="" target="_blank"></a> </div> <div class="floats-partial-caption-text"> <table> <tbody> <tr> <td>虚拟实验是进行启动在一天零,后来在一定时间间隔。在这种情况下,增加大约十周后已经完成。在浆细胞产生的抗体是派生通过扩大B细胞的克隆、注射抗原被清除和immunocomplexes形成。二次免疫反应提高比反应更强,更快的启动,因为免疫记忆(没有显示)。</tgydF4y2Bad> </tr> </tbody> </table> </div> </div> </div> </div> <p>而注射的免疫原性物质是主要负责免疫反应,次要的但不那么重要的因素是时间。事实上,如上预期,问题调查是最优时机提高抗体滴度较高。直觉,预计一个窗口的最优因为太近刺激不引起强烈的记忆,因为它简单地添加,'(和争夺资源),而过度延迟增加可能无法醒来的记忆,因为它已经消失了。计算机模拟允许轻松地扩大搜索最优,这将是昂贵和费时的动物模型。</gydF4y2Bap> <h4 id="validating-the-model-against-the-experimental-dataset">3所示。验证该模型对实验数据集</gydF4y2Bah4> <p>模拟器在使用之前,需要根据具体的实验数据进行验证和描述的部分<一个href="#sec2">2</一个>。有趣的是,匹配实验数据并不简单。事实上,第一组模拟不产生合理的符合的数据表明该模型缺乏一些具体机制。</gydF4y2Bap> <p>特别是模型未能正确再现动态间隙抗原和抗体扩张(不用说,这两个问题是连接)当我们获得比实验观察到的利率。指出我们讨论确定一个疫苗交付机制缺失的计算模型,可以解释观察到的差异。因此,为了解决这个矛盾,我们实现了两个机制:(i)来实现所谓的“得宝效应”,也就是说,逐渐释放的疫苗,以覆盖抗原暴露的很长一段时间,和(2)一种机制占immunocomplexes离解实际上提供了一个进一步博览会长时间注射疫苗。</gydF4y2Bap> <p>修改后的模型将这两个影响有效地增加了目标坚持实验数据。因为仓库效应导致轻微的差别,我们展示以下实施immunocomplexes离解的影响仿真结果。注意,抗原抗体复合物分离的整体预期效果是较长的博览会抗原和更好的亲和力成熟以来弱粘结剂分离率更高。具体来说,immunocomplexes的不稳定性(ICs)支持re-ingestion免疫原性肽的抗原呈递细胞(apc)和表示特定的淋巴细胞,谁,在他们一边,选择高亲和力的人。参见图<一个href="//www.newsama.com/journals/cmmm/2012/842329/fig3/" target="_blank">3</一个>比较抗体反应在三种不同情况下:没有与集成电路IC分离,分离后但没有直接摄入和演示与集成电路IC的巨噬细胞和离解但没有竞争机制集成电路消除的巨噬细胞。我们可以看到,如果没有IC离解,抗体滴度较低相比更高的抗原抗体的情况下不稳定而直接摄入的影响和IC的演讲后巨噬细胞并不占相同的重大影响但表明M IC摄入<年代vg height="13.425" id="M63" style="vertical-align:-2.29482pt;width:10.2px;" version="1.1" viewbox="0 0 10.2 13.425" width="10.2" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,13.425)"> <g transform="translate(72,-61.26)"> <text transform="matrix(1,0,0,-1,-71.95,63.6)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> </text> </g> </g> </svg>实际上代表了一种次优的情况相比,“整洁”IC离解,因为浪费的抗体绑定到抗原复合物中有效地丢弃巨噬细胞摄取。</gydF4y2Bap> <div class="partial-carousel-wrapper"> <div class="floats-partial-section"> <div class="floats-partial-content"> <div class="partial-carousel--full-image partial-carousel-64e4e43af9133799495f79d4c7115592"> <div class="partial-carousel--single-image"> <img loading="lazy" alt="" src="https://static.hindawi.com/articles/cmmm/volume-2012/842329/figures/842329.fig.003.jpg"> <br> <strong></strong> </div> </div> </div> <div class="floats-partial-middle"> <div class="floats-partial-middle--thumbs"> <div class="partial-carousel-dots-64e4e43af9133799495f79d4c7115592 partial-carousel-thumbnail"> <button aria-label="Slide to " class="partial-carousel-dot"><img loading="lazy" alt="" src="https://static.hindawi.com/articles/cmmm/volume-2012/842329/thumbnails/842329.fig.003_th.jpg"><br><strong></strong></button> </div> </div> <div class="floats-partial-middle--nav"> <div class="partial-carousel-next-prev-64e4e43af9133799495f79d4c7115592 partial-carousel-next-prev"> <button aria-label="Previous" class="carousel-prev"></button> <button aria-label="Next" class="carousel-next"></button> </div> </div> </div> <div class="floats-partial-footer"> <div class="floats-partial-caption"> <span class="caption-text">图3</年代pan> <a aria-label="View full page" class="caption-partial-url" href="//www.newsama.com/journals/cmmm/2012/842329/fig3/" title="" target="_blank"></a> </div> <div class="floats-partial-caption-text"> <table> <tbody> <tr> <td>离解immunocomplexes和连续吞噬作用和演示的装甲运兵车抗原分子增加疫苗持久性因此增加免疫反应的大小。</tgydF4y2Bad> </tr> </tbody> </table> </div> </div> </div> </div> <p>这些修改模拟器显示浓度与观察到的真实数据。图<一个href="//www.newsama.com/journals/cmmm/2012/842329/fig4/" target="_blank">4</一个>显示符合小鼠数据计算平均四只老鼠实验。误差的标准差免疫球蛋白抗体接受疫苗启动一天零,六个月后。图中的实线<一个href="//www.newsama.com/journals/cmmm/2012/842329/fig3/" target="_blank">3</一个>展示一个好的协议模拟老鼠的实验数据。</gydF4y2Bap> <div class="partial-carousel-wrapper"> <div class="floats-partial-section"> <div class="floats-partial-content"> <div class="partial-carousel--full-image partial-carousel-47d19d9b36cc80e3ba81872ec8a14bca"> <div class="partial-carousel--single-image"> <img loading="lazy" alt="" src="https://static.hindawi.com/articles/cmmm/volume-2012/842329/figures/842329.fig.004.jpg"> <br> <strong></strong> </div> </div> </div> <div class="floats-partial-middle"> <div class="floats-partial-middle--thumbs"> <div class="partial-carousel-dots-47d19d9b36cc80e3ba81872ec8a14bca partial-carousel-thumbnail"> <button aria-label="Slide to " class="partial-carousel-dot"><img loading="lazy" alt="" src="https://static.hindawi.com/articles/cmmm/volume-2012/842329/thumbnails/842329.fig.004_th.jpg"><br><strong></strong></button> </div> </div> <div class="floats-partial-middle--nav"> <div class="partial-carousel-next-prev-47d19d9b36cc80e3ba81872ec8a14bca partial-carousel-next-prev"> <button aria-label="Previous" class="carousel-prev"></button> <button aria-label="Next" class="carousel-next"></button> </div> </div> </div> <div class="floats-partial-footer"> <div class="floats-partial-caption"> <span class="caption-text">图4</年代pan> <a aria-label="View full page" class="caption-partial-url" href="//www.newsama.com/journals/cmmm/2012/842329/fig4/" title="" target="_blank"></a> </div> <div class="floats-partial-caption-text"> <table> <tbody> <tr> <td>与小鼠数据:抗体(免疫球蛋白)滴度平均相对标准偏差的四只老鼠实验。老鼠收到'注入在天0和提高六个月后。</tgydF4y2Bad> </tr> </tbody> </table> </div> </div> </div> </div> <p>这个数据集允许微调模拟器的参数。进一步的实验已经进行事后调查启动—提高时间距离之间的关系和免疫反应的大小测量免疫球蛋白抗体滴度。这是显示在接下来的部分。</gydF4y2Bap> <h4 id="results">4所示。结果</gydF4y2Bah4> <p>为了研究interdose延迟之间的关系和免疫反应,我们表现的一组虚拟实验通过运行仿真不同的初始条件。特别是,我们注入时间步的抗原<年代vg height="14.6" id="M64" style="vertical-align:-3.13504pt;width:38.3125px;" version="1.1" viewbox="0 0 38.3125 14.6" width="38.3125" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,14.6)"> <g transform="translate(72,-60.32)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> </text> <text transform="matrix(1,0,0,-1,-68.04,60.37)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 1</t年代pan> </text> <text transform="matrix(1,0,0,-1,-59.69,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> =</t年代pan> <tspan style="font-size: 12.50px; " x="12.027886" y="0"> 0</t年代pan> </text> </g> </g> </svg>并先后在<年代vg height="12.8875" id="M65" style="vertical-align:-3.13504pt;width:11.1125px;" version="1.1" viewbox="0 0 11.1125 12.8875" width="11.1125" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,12.8875)"> <g transform="translate(72,-61.69)"> <text transform="matrix(1,0,0,-1,-71.95,64.86)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> </text> <text transform="matrix(1,0,0,-1,-68.04,61.74)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 2</t年代pan> </text> </g> </g> </svg>。我们进行了模拟<年代vg height="10.325" id="M66" style="vertical-align:-0.0pt;width:11.225px;" version="1.1" viewbox="0 0 11.225 10.325" width="11.225" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,10.325)"> <g transform="translate(72,-63.74)"> <text transform="matrix(1,0,0,-1,-71.95,63.79)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> </text> </g> </g> </svg>时间步骤,相应的约<年代vg height="10.9125" id="M67" style="vertical-align:-0.17555pt;width:20.875px;" version="1.1" viewbox="0 0 20.875 10.9125" width="20.875" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,10.9125)"> <g transform="translate(72,-63.27)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> <tspan style="font-size: 12.50px; " x="6.8766499" y="0"> /</t年代pan> <tspan style="font-size: 12.50px; " x="10.352484" y="0"> 3</t年代pan> </text> </g> </g> </svg>天的真实的生活。延迟<年代vg height="14.575" id="M68" style="vertical-align:-3.21404pt;width:70.412498px;" version="1.1" viewbox="0 0 70.412498 14.575" width="70.412498" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,14.575)"> <g transform="translate(72,-60.34)"> <text transform="matrix(1,0,0,-1,-71.95,63.6)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> </text> <text transform="matrix(1,0,0,-1,-66.16,60.47)"> <tspan style="font-size: 8.75px; " x="0" y="0"> </t年代pan> </text> <text transform="matrix(1,0,0,-1,-59.45,63.6)"> <tspan style="font-size: 12.50px; " x="0" y="0"> =</t年代pan> <tspan style="font-size: 12.50px; " x="12.027886" y="0"> </t年代pan> </text> <text transform="matrix(1,0,0,-1,-43.5,60.47)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 2</t年代pan> </text> <text transform="matrix(1,0,0,-1,-35.85,63.6)"> <tspan style="font-size: 12.50px; " x="0" y="0"> −</t年代pan> <tspan style="font-size: 12.50px; " x="11.340221" y="0"> </t年代pan> </text> <text transform="matrix(1,0,0,-1,-20.59,60.47)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 1</t年代pan> </text> </g> </g> </svg>是实验的自由变量,而结果是产生的抗体量的差异'和提高疫苗接种。更具体地说,我们的电话<年代vg height="13.45" id="M69" style="vertical-align:-2.21957pt;width:30.612499px;" version="1.1" viewbox="0 0 30.612499 13.45" width="30.612499" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,13.45)"> <g transform="translate(72,-61.24)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> <tspan style="font-size: 12.50px; " x="6.2765059" y="0"> </t年代pan> <tspan style="font-size: 12.50px; " x="12.152916" y="0"> (</t年代pan> <tspan style="font-size: 12.50px; " x="16.316416" y="0"> </t年代pan> <tspan style="font-size: 12.50px; " x="20.229855" y="0"> )</t年代pan> </text> </g> </g> </svg>抗体滴度<年代vg height="9.125" id="M70" style="vertical-align:-0.11285pt;width:5.0124998px;" version="1.1" viewbox="0 0 5.0124998 9.125" width="5.0124998" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,9.125)"> <g transform="translate(72,-64.7)"> <text transform="matrix(1,0,0,-1,-71.95,64.86)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> </text> </g> </g> </svg>,<年代vg height="14.6625" id="M71" style="vertical-align:-3.13504pt;width:202.8625px;" version="1.1" viewbox="0 0 202.8625 14.6625" width="202.8625" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,14.6625)"> <g transform="translate(72,-60.27)"> <text transform="matrix(1,0,0,-1,-71.95,63.45)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> </text> <text transform="matrix(1,0,0,-1,-63.07,60.32)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 1</t年代pan> </text> <text transform="matrix(1,0,0,-1,-54.73,63.45)"> <tspan style="font-size: 12.50px; " x="0" y="0"> =</t年代pan> <tspan style="font-size: 12.50px; " x="12.040389" y="0"> 米</t年代pan> <tspan style="font-size: 12.50px; " x="21.767723" y="0"> 一个</t年代pan> <tspan style="font-size: 12.50px; " x="27.319056" y="0"> x</t年代pan> <tspan style="font-size: 12.50px; " x="39.822056" y="0"> {</t年代pan> <tspan style="font-size: 12.50px; " x="45.823494" y="0"> </t年代pan> <tspan style="font-size: 12.50px; " x="52.100002" y="0"> </t年代pan> <tspan style="font-size: 12.50px; " x="57.97641" y="0"> (</t年代pan> <tspan style="font-size: 12.50px; " x="62.139912" y="0"> </t年代pan> <tspan style="font-size: 12.50px; " x="66.053352" y="0"> )</t年代pan> <tspan style="font-size: 12.50px; " x="73.680176" y="0"> ∶</t年代pan> <tspan style="font-size: 12.50px; " x="83.545044" y="0"> </t年代pan> </text> <text transform="matrix(1,0,0,-1,32.74,60.32)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 1</t年代pan> </text> <text transform="matrix(1,0,0,-1,41.09,63.45)"> <tspan style="font-size: 12.50px; " x="0" y="0"> ∈</t年代pan> <tspan style="font-size: 12.50px; " x="12.027886" y="0"> (</t年代pan> <tspan style="font-size: 12.50px; " x="16.191385" y="0"> </t年代pan> </text> <text transform="matrix(1,0,0,-1,61.2,60.32)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 1</t年代pan> </text> <text transform="matrix(1,0,0,-1,66.07,63.45)"> <tspan style="font-size: 12.50px; " x="0" y="0"> ,</t年代pan> <tspan style="font-size: 12.50px; " x="5.2012482" y="0"> </t年代pan> </text> <text transform="matrix(1,0,0,-1,75.2,60.32)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 2</t年代pan> </text> <text transform="matrix(1,0,0,-1,80.07,63.45)"> <tspan style="font-size: 12.50px; " x="0" y="0"> )</t年代pan> <tspan style="font-size: 12.50px; " x="4.1634989" y="0"> }</t年代pan> </text> </g> </g> </svg>的最大水平<年代vg height="10.7375" id="M72" style="vertical-align:-0.13794pt;width:15.3125px;" version="1.1" viewbox="0 0 15.3125 10.7375" width="15.3125" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,10.7375)"> <g transform="translate(72,-63.41)"> <text transform="matrix(1,0,0,-1,-71.95,63.6)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> <tspan style="font-size: 12.50px; " x="6.2765059" y="0"> </t年代pan> </text> </g> </g> </svg>相对于注射抗原<年代vg height="13.05" id="M73" style="vertical-align:-3.25793pt;width:11.1125px;" version="1.1" viewbox="0 0 11.1125 13.05" width="11.1125" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,13.05)"> <g transform="translate(72,-61.56)"> <text transform="matrix(1,0,0,-1,-71.95,64.86)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> </text> <text transform="matrix(1,0,0,-1,-68.04,61.74)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 0</t年代pan> </text> </g> </g> </svg>(即。,the prime injection), and analogously<年代vg height="14.6625" id="M74" style="vertical-align:-3.13504pt;width:194.375px;" version="1.1" viewbox="0 0 194.375 14.6625" width="194.375" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,14.6625)"> <g transform="translate(72,-60.27)"> <text transform="matrix(1,0,0,-1,-71.95,63.45)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> </text> <text transform="matrix(1,0,0,-1,-63.07,60.32)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 2</t年代pan> </text> <text transform="matrix(1,0,0,-1,-54.73,63.45)"> <tspan style="font-size: 12.50px; " x="0" y="0"> =</t年代pan> <tspan style="font-size: 12.50px; " x="12.040389" y="0"> 米</t年代pan> <tspan style="font-size: 12.50px; " x="21.767723" y="0"> 一个</t年代pan> <tspan style="font-size: 12.50px; " x="27.319056" y="0"> x</t年代pan> <tspan style="font-size: 12.50px; " x="39.822056" y="0"> {</t年代pan> <tspan style="font-size: 12.50px; " x="45.823494" y="0"> </t年代pan> <tspan style="font-size: 12.50px; " x="52.100002" y="0"> </t年代pan> <tspan style="font-size: 12.50px; " x="57.97641" y="0"> (</t年代pan> <tspan style="font-size: 12.50px; " x="62.139912" y="0"> </t年代pan> <tspan style="font-size: 12.50px; " x="66.053352" y="0"> )</t年代pan> <tspan style="font-size: 12.50px; " x="73.680176" y="0"> ∶</t年代pan> <tspan style="font-size: 12.50px; " x="83.545044" y="0"> </t年代pan> <tspan style="font-size: 12.50px; " x="90.934319" y="0"> ∈</t年代pan> <tspan style="font-size: 12.50px; " x="102.97471" y="0"> (</t年代pan> <tspan style="font-size: 12.50px; " x="107.13821" y="0"> </t年代pan> </text> <text transform="matrix(1,0,0,-1,56.33,60.32)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 2</t年代pan> </text> <text transform="matrix(1,0,0,-1,61.2,63.45)"> <tspan style="font-size: 12.50px; " x="0" y="0"> ,</t年代pan> <tspan style="font-size: 12.50px; " x="5.2012482" y="0"> </t年代pan> <tspan style="font-size: 12.50px; " x="12.077898" y="0"> ]</t年代pan> <tspan style="font-size: 12.50px; " x="16.241398" y="0"> }</t年代pan> </text> </g> </g> </svg>最大的免疫球蛋白水平相对于注射抗原的抗体<年代vg height="12.8875" id="M75" style="vertical-align:-3.13504pt;width:11.1125px;" version="1.1" viewbox="0 0 11.1125 12.8875" width="11.1125" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,12.8875)"> <g transform="translate(72,-61.69)"> <text transform="matrix(1,0,0,-1,-71.95,64.86)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> </text> <text transform="matrix(1,0,0,-1,-68.04,61.74)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 2</t年代pan> </text> </g> </g> </svg>(即。,the boost injection). We can assume that<年代vg height="13.55" id="M76" style="vertical-align:-3.13504pt;width:53.887501px;" version="1.1" viewbox="0 0 53.887501 13.55" width="53.887501" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,13.55)"> <g transform="translate(72,-61.16)"> <text transform="matrix(1,0,0,-1,-71.95,64.34)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> </text> <text transform="matrix(1,0,0,-1,-63.07,61.21)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 1</t年代pan> </text> <text transform="matrix(1,0,0,-1,-54.73,64.34)"> <tspan style="font-size: 12.50px; " x="0" y="0"> ≤</t年代pan> <tspan style="font-size: 12.50px; " x="12.040389" y="0"> </t年代pan> </text> <text transform="matrix(1,0,0,-1,-33.81,61.21)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 2</t年代pan> </text> </g> </g> </svg>自注射抗原注射是相同的两个,因此,免疫记忆是第二个免疫反应更快,比第一(<一个href="#B33">33</一个>,<一个href="#B34">34</一个>]。</gydF4y2Bap> <p>我们称之为<年代vg height="14.6875" id="M77" style="vertical-align:-3.2316pt;width:94.087502px;" version="1.1" viewbox="0 0 94.087502 14.6875" width="94.087502" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,14.6875)"> <g transform="translate(72,-60.25)"> <text transform="matrix(1,0,0,-1,-71.95,63.52)"> <tspan style="font-size: 12.50px; " x="0" y="0"> Δ</t年代pan> </text> <text transform="matrix(1,0,0,-1,-62.92,60.4)"> <tspan style="font-size: 8.75px; " x="0" y="0"> </t年代pan> <tspan style="font-size: 8.75px; " x="4.3935041" y="0"> </t年代pan> </text> <text transform="matrix(1,0,0,-1,-50.44,63.52)"> <tspan style="font-size: 12.50px; " x="0" y="0"> =</t年代pan> <tspan style="font-size: 12.50px; " x="12.027886" y="0"> </t年代pan> </text> <text transform="matrix(1,0,0,-1,-29.53,60.4)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 2</t年代pan> </text> <text transform="matrix(1,0,0,-1,-21.88,63.52)"> <tspan style="font-size: 12.50px; " x="0" y="0"> −</t年代pan> <tspan style="font-size: 12.50px; " x="11.340221" y="0"> </t年代pan> </text> <text transform="matrix(1,0,0,-1,-1.66,60.4)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 1</t年代pan> </text> </g> </g> </svg>抗体滴度的高峰值的差异在两个反应。自<年代vg height="12.8875" id="M78" style="vertical-align:-3.13504pt;width:11.1125px;" version="1.1" viewbox="0 0 11.1125 12.8875" width="11.1125" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,12.8875)"> <g transform="translate(72,-61.69)"> <text transform="matrix(1,0,0,-1,-71.95,64.86)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> </text> <text transform="matrix(1,0,0,-1,-68.04,61.74)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 1</t年代pan> </text> </g> </g> </svg>是固定的,<年代vg height="14.6" id="M79" style="vertical-align:-3.13504pt;width:38.3125px;" version="1.1" viewbox="0 0 38.3125 14.6" width="38.3125" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,14.6)"> <g transform="translate(72,-60.32)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> </text> <text transform="matrix(1,0,0,-1,-68.04,60.37)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 1</t年代pan> </text> <text transform="matrix(1,0,0,-1,-59.69,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> =</t年代pan> <tspan style="font-size: 12.50px; " x="12.027886" y="0"> 0</t年代pan> </text> </g> </g> </svg>和<年代vg height="10.925" id="M80" style="vertical-align:-3.13504pt;width:17.3125px;" version="1.1" viewbox="0 0 17.3125 10.925" width="17.3125" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,10.925)"> <g transform="translate(72,-63.26)"> <text transform="matrix(1,0,0,-1,-71.95,66.44)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> </text> <text transform="matrix(1,0,0,-1,-63.07,63.31)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 1</t年代pan> </text> </g> </g> </svg>和<年代vg height="10.925" id="M81" style="vertical-align:-3.13504pt;width:17.3125px;" version="1.1" viewbox="0 0 17.3125 10.925" width="17.3125" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,10.925)"> <g transform="translate(72,-63.26)"> <text transform="matrix(1,0,0,-1,-71.95,66.44)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> </text> <text transform="matrix(1,0,0,-1,-63.07,63.31)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 2</t年代pan> </text> </g> </g> </svg>依赖于时间的第二次注射<年代vg height="12.8875" id="M82" style="vertical-align:-3.13504pt;width:11.1125px;" version="1.1" viewbox="0 0 11.1125 12.8875" width="11.1125" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,12.8875)"> <g transform="translate(72,-61.69)"> <text transform="matrix(1,0,0,-1,-71.95,64.86)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> </text> <text transform="matrix(1,0,0,-1,-68.04,61.74)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 2</t年代pan> </text> </g> </g> </svg>我们有,<年代vg height="14.575" id="M83" style="vertical-align:-3.21404pt;width:41.775002px;" version="1.1" viewbox="0 0 41.775002 14.575" width="41.775002" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,14.575)"> <g transform="translate(72,-60.34)"> <text transform="matrix(1,0,0,-1,-71.95,63.6)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> </text> <text transform="matrix(1,0,0,-1,-66.16,60.47)"> <tspan style="font-size: 8.75px; " x="0" y="0"> </t年代pan> </text> <text transform="matrix(1,0,0,-1,-59.45,63.6)"> <tspan style="font-size: 12.50px; " x="0" y="0"> =</t年代pan> <tspan style="font-size: 12.50px; " x="12.027886" y="0"> </t年代pan> </text> <text transform="matrix(1,0,0,-1,-43.5,60.47)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 2</t年代pan> </text> </g> </g> </svg>,<年代vg height="14.6" id="M84" style="vertical-align:-3.13504pt;width:75.287498px;" version="1.1" viewbox="0 0 75.287498 14.6" width="75.287498" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,14.6)"> <g transform="translate(72,-60.32)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> </text> <text transform="matrix(1,0,0,-1,-63.07,60.37)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 2</t年代pan> </text> <text transform="matrix(1,0,0,-1,-54.73,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> ≡</t年代pan> <tspan style="font-size: 12.50px; " x="12.040389" y="0"> </t年代pan> </text> <text transform="matrix(1,0,0,-1,-33.81,60.37)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 2</t年代pan> </text> <text transform="matrix(1,0,0,-1,-28.94,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> (</t年代pan> <tspan style="font-size: 12.50px; " x="4.1634989" y="0"> </t年代pan> </text> <text transform="matrix(1,0,0,-1,-20.86,60.37)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 2</t年代pan> </text> <text transform="matrix(1,0,0,-1,-15.99,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> )</t年代pan> </text> </g> </g> </svg>和<年代vg height="14.7125" id="M85" style="vertical-align:-3.2316pt;width:85.987503px;" version="1.1" viewbox="0 0 85.987503 14.7125" width="85.987503" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,14.7125)"> <g transform="translate(72,-60.23)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> Δ</t年代pan> </text> <text transform="matrix(1,0,0,-1,-62.92,60.37)"> <tspan style="font-size: 8.75px; " x="0" y="0"> </t年代pan> <tspan style="font-size: 8.75px; " x="4.3935041" y="0"> </t年代pan> </text> <text transform="matrix(1,0,0,-1,-50.44,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> ≡</t年代pan> <tspan style="font-size: 12.50px; " x="12.027886" y="0"> Δ</t年代pan> </text> <text transform="matrix(1,0,0,-1,-29.38,60.37)"> <tspan style="font-size: 8.75px; " x="0" y="0"> </t年代pan> <tspan style="font-size: 8.75px; " x="4.3935041" y="0"> </t年代pan> </text> <text transform="matrix(1,0,0,-1,-20.37,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> (</t年代pan> <tspan style="font-size: 12.50px; " x="4.1634989" y="0"> </t年代pan> </text> <text transform="matrix(1,0,0,-1,-12.3,60.37)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 2</t年代pan> </text> <text transform="matrix(1,0,0,-1,-7.42,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> )</t年代pan> </text> </g> </g> </svg>。</gydF4y2Bap> <p>在图<一个href="//www.newsama.com/journals/cmmm/2012/842329/fig5/" target="_blank">5</一个>,我们显示箱线图比较<年代vg height="14.6" id="M86" style="vertical-align:-3.13504pt;width:35.537498px;" version="1.1" viewbox="0 0 35.537498 14.6" width="35.537498" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,14.6)"> <g transform="translate(72,-60.32)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> </text> <text transform="matrix(1,0,0,-1,-63.07,60.37)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 1</t年代pan> </text> <text transform="matrix(1,0,0,-1,-58.2,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> (</t年代pan> <tspan style="font-size: 12.50px; " x="4.1634989" y="0"> 0</t年代pan> <tspan style="font-size: 12.50px; " x="10.414999" y="0"> )</t年代pan> </text> </g> </g> </svg>和<年代vg height="14.6" id="M87" style="vertical-align:-3.13504pt;width:38.712502px;" version="1.1" viewbox="0 0 38.712502 14.6" width="38.712502" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,14.6)"> <g transform="translate(72,-60.32)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> </text> <text transform="matrix(1,0,0,-1,-63.07,60.37)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 2</t年代pan> </text> <text transform="matrix(1,0,0,-1,-58.2,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> (</t年代pan> <tspan style="font-size: 12.50px; " x="4.1634989" y="0"> </t年代pan> </text> <text transform="matrix(1,0,0,-1,-50.12,60.37)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 2</t年代pan> </text> <text transform="matrix(1,0,0,-1,-45.25,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> )</t年代pan> </text> </g> </g> </svg>为不同的值<年代vg height="14.575" id="M88" style="vertical-align:-3.21404pt;width:41.775002px;" version="1.1" viewbox="0 0 41.775002 14.575" width="41.775002" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,14.575)"> <g transform="translate(72,-60.34)"> <text transform="matrix(1,0,0,-1,-71.95,63.6)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> </text> <text transform="matrix(1,0,0,-1,-66.16,60.47)"> <tspan style="font-size: 8.75px; " x="0" y="0"> </t年代pan> </text> <text transform="matrix(1,0,0,-1,-59.45,63.6)"> <tspan style="font-size: 12.50px; " x="0" y="0"> =</t年代pan> <tspan style="font-size: 12.50px; " x="12.027886" y="0"> </t年代pan> </text> <text transform="matrix(1,0,0,-1,-43.5,60.47)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 2</t年代pan> </text> </g> </g> </svg>。这是计算平均超过20 10微升体积的模拟。较低的面板的图表明,除了大型的随机波动,<年代vg height="14.6" id="M89" style="vertical-align:-3.13504pt;width:90.962502px;" version="1.1" viewbox="0 0 90.962502 14.6" width="90.962502" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,14.6)"> <g transform="translate(72,-60.32)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> </text> <text transform="matrix(1,0,0,-1,-63.07,60.37)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 1</t年代pan> </text> <text transform="matrix(1,0,0,-1,-58.2,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> (</t年代pan> <tspan style="font-size: 12.50px; " x="4.1634989" y="0"> </t年代pan> </text> <text transform="matrix(1,0,0,-1,-50.12,60.37)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 2</t年代pan> </text> <text transform="matrix(1,0,0,-1,-45.25,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> )</t年代pan> <tspan style="font-size: 12.50px; " x="7.6268301" y="0"> =</t年代pan> <tspan style="font-size: 12.50px; " x="19.667219" y="0"> c</t年代pan> <tspan style="font-size: 12.50px; " x="25.218552" y="0"> o</t年代pan> <tspan style="font-size: 12.50px; " x="31.470051" y="0"> n</t年代pan> <tspan style="font-size: 12.50px; " x="37.72155" y="0"> 年代</t年代pan> <tspan style="font-size: 12.50px; " x="42.497696" y="0"> t</t年代pan> </text> </g> </g> </svg>,也就是说,它是独立的<年代vg height="12.8875" id="M90" style="vertical-align:-3.13504pt;width:11.1125px;" version="1.1" viewbox="0 0 11.1125 12.8875" width="11.1125" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,12.8875)"> <g transform="translate(72,-61.69)"> <text transform="matrix(1,0,0,-1,-71.95,64.86)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> </text> <text transform="matrix(1,0,0,-1,-68.04,61.74)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 2</t年代pan> </text> </g> </g> </svg>,而上部面板显示<年代vg height="14.6" id="M91" style="vertical-align:-3.13504pt;width:38.712502px;" version="1.1" viewbox="0 0 38.712502 14.6" width="38.712502" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,14.6)"> <g transform="translate(72,-60.32)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> </text> <text transform="matrix(1,0,0,-1,-63.07,60.37)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 2</t年代pan> </text> <text transform="matrix(1,0,0,-1,-58.2,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> (</t年代pan> <tspan style="font-size: 12.50px; " x="4.1634989" y="0"> </t年代pan> </text> <text transform="matrix(1,0,0,-1,-50.12,60.37)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 2</t年代pan> </text> <text transform="matrix(1,0,0,-1,-45.25,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> )</t年代pan> </text> </g> </g> </svg>告诉,总的来说,存在一个最佳的时机的提高大于45天。</gydF4y2Bap> <div class="partial-carousel-wrapper"> <div class="floats-partial-section"> <div class="floats-partial-content"> <div class="partial-carousel--full-image partial-carousel-43dee7d4b3f27ceae3671a985a25c910"> <div class="partial-carousel--single-image"> <img loading="lazy" alt="(一)gydF4y2Ba" src="https://static.hindawi.com/articles/cmmm/volume-2012/842329/figures/842329.fig.005a.jpg"> <br> <strong>(一)</年代trong> </div> <div class="partial-carousel--single-image"> <img loading="lazy" alt="(b)gydF4y2Ba" src="https://static.hindawi.com/articles/cmmm/volume-2012/842329/figures/842329.fig.005b.jpg"> <br> <strong>(b)</年代trong> </div> </div> </div> <div class="floats-partial-middle"> <div class="floats-partial-middle--thumbs"> <div class="partial-carousel-dots-43dee7d4b3f27ceae3671a985a25c910 partial-carousel-thumbnail"> <button aria-label="Slide to (a) " class="partial-carousel-dot"><img loading="lazy" alt="(一)gydF4y2Ba" src="https://static.hindawi.com/articles/cmmm/volume-2012/842329/thumbnails/842329.fig.005a_th.jpg"><br><strong>(一)</年代trong></button> <button aria-label="Slide to (b) " class="partial-carousel-dot"><img loading="lazy" alt="(b)gydF4y2Ba" src="https://static.hindawi.com/articles/cmmm/volume-2012/842329/thumbnails/842329.fig.005b_th.jpg"><br><strong>(b)</年代trong></button> </div> </div> <div class="floats-partial-middle--nav"> <div class="partial-carousel-next-prev-43dee7d4b3f27ceae3671a985a25c910 partial-carousel-next-prev"> <button aria-label="Previous" class="carousel-prev"></button> <button aria-label="Next" class="carousel-next"></button> </div> </div> </div> <div class="floats-partial-footer"> <div class="floats-partial-caption"> <span class="caption-text">图5</年代pan> <a aria-label="View full page" class="caption-partial-url" href="//www.newsama.com/journals/cmmm/2012/842329/fig5/" title="" target="_blank"></a> </div> <div class="floats-partial-caption-text"> <table> <tbody> <tr> <td>较低的面板显示<年代vg height="10.925" id="M92" style="vertical-align:-3.13504pt" version="1.1" viewbox="0 0 17.3125 10.925" width="17.3125" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,10.925)"> <g transform="translate(72,-63.26)"> <text transform="matrix(1,0,0,-1,-71.95,66.44)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> </text> <text transform="matrix(1,0,0,-1,-63.07,63.31)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 1</t年代pan> </text> </g> </g> </svg>是非常独立的<年代vg height="12.8875" id="M93" style="vertical-align:-3.13504pt" version="1.1" viewbox="0 0 11.1125 12.8875" width="11.1125" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,12.8875)"> <g transform="translate(72,-61.69)"> <text transform="matrix(1,0,0,-1,-71.95,64.86)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> </text> <text transform="matrix(1,0,0,-1,-68.04,61.74)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 2</t年代pan> </text> </g> </g> </svg>而上部面板显示<年代vg height="10.925" id="M94" style="vertical-align:-3.13504pt" version="1.1" viewbox="0 0 17.3125 10.925" width="17.3125" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,10.925)"> <g transform="translate(72,-63.26)"> <text transform="matrix(1,0,0,-1,-71.95,66.44)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> </text> <text transform="matrix(1,0,0,-1,-63.07,63.31)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 2</t年代pan> </text> </g> </g> </svg>告诉,总的来说,存在一个最佳的时机的提高大于45天。</tgydF4y2Bad> </tr> </tbody> </table> </div> </div> </div> </div> <p>相同的信息显示在图<一个href="//www.newsama.com/journals/cmmm/2012/842329/fig6/" target="_blank">6</一个>这情节<年代vg height="14.7125" id="M95" style="vertical-align:-3.2316pt;width:44.362499px;" version="1.1" viewbox="0 0 44.362499 14.7125" width="44.362499" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,14.7125)"> <g transform="translate(72,-60.23)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> Δ</t年代pan> </text> <text transform="matrix(1,0,0,-1,-62.92,60.37)"> <tspan style="font-size: 8.75px; " x="0" y="0"> </t年代pan> <tspan style="font-size: 8.75px; " x="4.3935041" y="0"> </t年代pan> </text> <text transform="matrix(1,0,0,-1,-53.92,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> (</t年代pan> <tspan style="font-size: 12.50px; " x="4.1634989" y="0"> </t年代pan> </text> <text transform="matrix(1,0,0,-1,-43.97,60.37)"> <tspan style="font-size: 8.75px; " x="0" y="0"> </t年代pan> </text> <text transform="matrix(1,0,0,-1,-40.73,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> )</t年代pan> </text> </g> </g> </svg>的函数<年代vg height="14.575" id="M96" style="vertical-align:-3.21404pt;width:41.775002px;" version="1.1" viewbox="0 0 41.775002 14.575" width="41.775002" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,14.575)"> <g transform="translate(72,-60.34)"> <text transform="matrix(1,0,0,-1,-71.95,63.6)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> </text> <text transform="matrix(1,0,0,-1,-66.16,60.47)"> <tspan style="font-size: 8.75px; " x="0" y="0"> </t年代pan> </text> <text transform="matrix(1,0,0,-1,-59.45,63.6)"> <tspan style="font-size: 12.50px; " x="0" y="0"> =</t年代pan> <tspan style="font-size: 12.50px; " x="12.027886" y="0"> </t年代pan> </text> <text transform="matrix(1,0,0,-1,-43.5,60.47)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 2</t年代pan> </text> </g> </g> </svg>。特别是,间隔几周总理和提高需要获得一个最优的体液反应,假设和实验研究报告。的确,当刺激后的第一个月',次要的山峰之间的区别和主反应,这是一个衡量的效率提高,相当低。提高效率增加当第二个剂量后45到90天',而进一步推迟提高并不能提高二级抗体高峰。</gydF4y2Bap> <div class="partial-carousel-wrapper"> <div class="floats-partial-section"> <div class="floats-partial-content"> <div class="partial-carousel--full-image partial-carousel-3919258fae6ce0dc9d4f52ce51ec8e7f"> <div class="partial-carousel--single-image"> <img loading="lazy" alt="" src="https://static.hindawi.com/articles/cmmm/volume-2012/842329/figures/842329.fig.006.jpg"> <br> <strong></strong> </div> </div> </div> <div class="floats-partial-middle"> <div class="floats-partial-middle--thumbs"> <div class="partial-carousel-dots-3919258fae6ce0dc9d4f52ce51ec8e7f partial-carousel-thumbnail"> <button aria-label="Slide to " class="partial-carousel-dot"><img loading="lazy" alt="" src="https://static.hindawi.com/articles/cmmm/volume-2012/842329/thumbnails/842329.fig.006_th.jpg"><br><strong></strong></button> </div> </div> <div class="floats-partial-middle--nav"> <div class="partial-carousel-next-prev-3919258fae6ce0dc9d4f52ce51ec8e7f partial-carousel-next-prev"> <button aria-label="Previous" class="carousel-prev"></button> <button aria-label="Next" class="carousel-next"></button> </div> </div> </div> <div class="floats-partial-footer"> <div class="floats-partial-caption"> <span class="caption-text">图6</年代pan> <a aria-label="View full page" class="caption-partial-url" href="//www.newsama.com/journals/cmmm/2012/842329/fig6/" title="" target="_blank"></a> </div> <div class="floats-partial-caption-text"> <table> <tbody> <tr> <td>当提升后的第一个月',我们测量的效率提高,<年代vg height="14.7125" id="M97" style="vertical-align:-3.2316pt" version="1.1" viewbox="0 0 44.362499 14.7125" width="44.362499" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,14.7125)"> <g transform="translate(72,-60.23)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> Δ</t年代pan> </text> <text transform="matrix(1,0,0,-1,-62.92,60.37)"> <tspan style="font-size: 8.75px; " x="0" y="0"> </t年代pan> <tspan style="font-size: 8.75px; " x="4.3935041" y="0"> </t年代pan> </text> <text transform="matrix(1,0,0,-1,-53.92,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> (</t年代pan> <tspan style="font-size: 12.50px; " x="4.1634989" y="0"> </t年代pan> </text> <text transform="matrix(1,0,0,-1,-43.97,60.37)"> <tspan style="font-size: 8.75px; " x="0" y="0"> </t年代pan> </text> <text transform="matrix(1,0,0,-1,-40.73,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> )</t年代pan> </text> </g> </g> </svg>很低而增加当第二个剂量后45到90天'。</tgydF4y2Bad> </tr> </tbody> </table> </div> </div> </div> </div> <h4 id="discussion">5。讨论</gydF4y2Bah4> <p>优化启动—提高方案是开发新型疫苗的关键。的最佳时间是什么推动是一项基本问题仍未得到回答(<一个href="#B4">4</一个>]。有人建议,间隔至少2 - 3个月'和提高需要获得最佳反应,记忆T细胞增殖潜力不高形式,直到几周后第一次免疫,和记忆<年代vg height="10.325" id="M98" style="vertical-align:-0.0pt;width:11.625px;" version="1.1" viewbox="0 0 11.625 10.325" width="11.625" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,10.325)"> <g transform="translate(72,-63.74)"> <text transform="matrix(1,0,0,-1,-71.95,63.79)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代pan> </text> </g> </g> </svg>细胞的生发中心反应,需要几个月的时间来开发<一个href="#B4">4</一个>]。</gydF4y2Bap> <p>免疫程序设计经验,然后提炼的基础上观察到的免疫反应和保护。在某些情况下,不同的国家,实现相同的疫苗纳入国家免疫程序使用不同的时间表<一个href="#B35">35</一个>,<一个href="#B36">36</一个>]。</gydF4y2Bap> <p>美国免疫实践咨询委员会(ACIP)每年发布一个推荐免疫程序许可的疫苗,以反映当前的建议(<一个href="#B37">37</一个>,<一个href="#B38">38</一个>]。为个人的疫苗接种计划已被推迟,赶上日程和最小剂量之间的间隔是表示(<一个href="#B37">37</一个>]。对于大多数目前使用的疫苗,最低推荐剂量间隔1和2,为了孩子,是4周,但是,对于一些疫苗至少8周的间隔,建议3个月或6个月(<一个href="#B37">37</一个>]。</gydF4y2Bap> <p>疫苗的临床前实验原型,另一方面,常常使用剂量间隔时间短,获得快速增长抗体滴度高于保护值。疫苗接种的β-淀粉样蛋白在阿尔茨海默病小鼠模型,一个时间表已经使用各种原型疫苗包括剂量在第0天,2周,4周,月度剂量。当多个剂量管理在短时间内,了解每一个剂量的贡献峰值抗体效价可以几乎不可能。</gydF4y2Bap> <p>在这项研究中,我们分析了影响'之间的间隔,提高注射抗体反应的免疫系统的计算模型。</gydF4y2Bap> <p>我们已经表明,在计算模型中一个间隔之间的几周总理和提高是必要的获得最优反应,推测和报道真实的免疫反应。特别是,在模拟,给出提高后的第一个月,二级的山峰之间的区别和主反应,我们测量的效率提高,很低。提高效率增加当第二个剂量后45到90天',而进一步推迟提高并不能提高二级抗体(模拟峰值提高管理后300天'如图<一个href="//www.newsama.com/journals/cmmm/2012/842329/fig6/" target="_blank">6</一个>)。</gydF4y2Bap> <p>因此,计算模型显示真正的免疫反应的定性特征,它可以是非常有用的理解哪个组件的免疫系统负责观察的时间提高疗效的差异<gydF4y2Bai>在活的有机体内</gydF4y2Bai>。有趣的是,提高的功效不平行辅助T细胞和B细胞的数量。在模型中,T细胞和B细胞数量的增加'后,细胞被激活和复制。细胞数量下降,细胞死亡的结果。因此,一天15 T、B细胞多于90天。有趣的是,还记忆T细胞在15 - 45的时间更丰富点比以后点,显示在之后的时间点获得更好的记忆反应是不相关的更高的记忆T细胞的数量。相反,促进最佳时间点,生成的人群'特别是,激活细胞,细胞复制,而且记忆细胞,都感染了。存在的T细胞和B细胞后的系统在后期时间点'细胞与之前有很大的不同。这里强调是很重要的,在模型中,记忆细胞是细胞,激活抗原,其平均寿命增加。进一步接触抗原导致进一步增加寿命。 Thus, memory cells are not all equal in their proliferative potential, and the memory of the system matures over time, as cells with high proliferative capacity are generated. This model, therefore, demonstrates that cell populations dynamics, and a simple assumption, namely the fact that a “survival signal” is received by memory cells at each encounter with antigen, are sufficient to reproduce the need for an optimal delay between prime and boost, observed<i>体内。</gydF4y2Bai></p> <p>另一方面,不同疫苗已知不同的需求对剂量之间的最小间隔。模拟在本研究报告指“通用疫苗,”和获得的时间尺度,这是很现实的,反正不指一个特定的疫苗,虽然参数设置为适合数据获得当时蛋白质抗原,即病毒样颗粒(1 - 11)E2(6)。计算模型可以探索不同的角色功能的主要响应刺激的最佳时间点,提高效率,在设定的时间点。</gydF4y2Bap> <p>深入分析整个系统的动力学目前正在确定哪些免疫组件负责观察到的行为,将适时公布。此外,疫苗特异性肽的数量很可能会扮演不同的角色的追求最优,因此他们必须被纳入计算机模型。</gydF4y2Bap> <h4 id="author’s-contribution">作者的贡献</gydF4y2Bah4> <p>p . De Berardinis和a . Prisco同样导致了这项研究。</gydF4y2Bap> <h4 id="acknowledgments">确认</gydF4y2Bah4> <p>答:Prisco承认支持FIRB-Merit RBNE08LN4P_002。p . 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Prinja和m .拉其普特人”引入第二剂麻疹在印度国家免疫计划:根除了一大步,”<gydF4y2Bai>人类疫苗</gydF4y2Bai>,7卷,不。10日,1109 - 1111年,2011页。</gydF4y2Bap>视图:<gydF4y2Ba!-- --> <a href="https://scholar.google.com/scholar_lookup?title=Introduction%20of%20a%20second%20dose%20of%20measles%20in%20national%20immunization%20program%20in%20India%3A%20a%20major%20step%20towards%20eradication&author=R.%20Verma&author=P.%20Khanna&author=M.%20Bairwa&author=S.%20Chawla&author=S.%20Prinja&author=M.%20Rajput&publication_year=2011" target="_blank" rel="noreferrer">谷歌学术搜索</一个> </div></li> <li class="ArticleReferences_articleReference__ouEuh" id="B37"> <div class="referenceContent"> <p class="referenceText">疾病控制和预防中心”推荐免疫程序人员0到18岁years-United州,2012年,“<gydF4y2Bai>发病率和死亡率每周报告</gydF4y2Bai>,卷61,不。5,页1 - 4,2012。</gydF4y2Bap>视图:<gydF4y2Ba!-- --> <a href="https://scholar.google.com/scholar_lookup?title=Recommended%20immunization%20schedules%20for%20persons%20aged%200%20through%2018%20years%E2%80%94United%20States%2C%202012&author=%20Centers%20for%20Disease%20Control&author=Prevention&publication_year=2012" target="_blank" rel="noreferrer">谷歌学术搜索</一个> </div></li> <li class="ArticleReferences_articleReference__ouEuh" id="B38"> <div class="referenceContent"> <p class="referenceText">j .助产学“推荐成人免疫schedule&United州,2012年,“<gydF4y2Bai>疾病控制和预防中心。女性健康</gydF4y2Bai>卷,57号2、188 - 195年,2012页。</gydF4y2Bap>视图:<gydF4y2Ba!-- --> <a href="https://scholar.google.com/scholar_lookup?title=Recommended%20adult%20immunization%20schedule%26United%20States%2C%202012&author=J.%20Midwifery&publication_year=2012" target="_blank" rel="noreferrer">谷歌学术搜索</一个> </div></li> </ol> </div> <h4 class="copyright-title" id="copyright">版权</gydF4y2Bah4> <div class="copyright-body"> 版权©2012 F。马匹等。这是一个开放的分布式下文章<一个rel="license" 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