疟原虫Riboprotein PfP0引发一个异常Balb / c小鼠的体液免疫反应</t我tle> <link rel="preload stylesheet" as="style" type="text/css" href="https://cdn.bibblio.org/rcm/4.28.0/bib-related-content.min.css"> <link rel="preload" href="https://static.hindawi.com/new/next_assets/2023-08-03-0017a694320dbe69a559e8120be98c/_next/static/css/b2661f2cd4bd618b.css" as="style"> <link rel="stylesheet" href="https://static.hindawi.com/new/next_assets/2023-08-03-0017a694320dbe69a559e8120be98c/_next/static/css/b2661f2cd4bd618b.css" data-n-g=""> <style id="__jsx-903e4b2e5d3241e4">div#__next{display:-webkit-box;display:-webkit-flex;display:-moz-box;display:-ms-flexbox;display:flex;min-height:100vh;-webkit-box-orient:vertical;-webkit-box-direction:normal;-webkit-flex-direction:column;-moz-box-orient:vertical;-moz-box-direction:normal;-ms-flex-direction:column;flex-direction:column}</style> </head> <body> <div id="__next"> <section class="ant-layout"> <div> <header class="ant-layout-header"> <div class="header__width-wrapper"> <div 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</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p一个n> <h2 class="articleHeader__specialIssue_title">2011年寄生虫病免疫学和细胞生物学</h2> <a href="//www.newsama.com/journals/bmri/si/824978/" class="articleHeader__specialIssue_url" target="_blank" rel="noreferrer">把这个特殊的问题</一个> </div> <strong>研究文章|开放获取</年代trong> <div class="articleHeader__meta"> <span>体积2012年|</年代p一个n> <span>文章的ID695843年|</年代p一个n> <span class="articleHeader__meta_doiLink"><a href="https://doi.org/10.1155/2012/695843" aria-label="Doi-link" target="_blank" rel="noreferrer">https://doi.org/10.1155/2012/695843</一个></span> </div> <div class="simpleShowMore"> <button class="simpleShowMore__button">显示引用</button> </div> <h1 class="articleHeader__title"><i>疟原虫</我>Riboprotein PfP0诱发Balb /异常体液免疫反应<我>c</我>老鼠</h1> <div class="articleHeader__authors"> <span class="articleHeader__authors_author"><strong>Sulabha帕沙克</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">k . Rajeshwari,<年代up>1、2</年代up></span> <span class="articleHeader__authors_author">斯瓦特Garg,<年代up>1</年代up></span> <span class="articleHeader__authors_author">Sudarsan Rajagopal,<年代up>1</年代up></span> <span class="articleHeader__authors_author">Kalpesh帕特尔,<年代up>1、3</年代up></span> <span class="articleHeader__authors_author">Bidyut Das,<年代up>4</年代up></span> <span class="articleHeader__authors_author">方法斑驳的,<年代up>5</年代up></span> <span class="articleHeader__authors_author">Balachandran文德兰花,<年代up>6</年代up></span> <span class="articleHeader__authors_author">和Shobhona沙玛<年代up>1</年代up></span> </div> <div class="simpleShowMore"> <button class="simpleShowMore__button">显示更多</button> </div> <div class="articleHeader__academicEditor"> <strong>学术编辑器:</年代trong> <span>Jorge Morales-Montor</年代p一个n> </div> <div class="articleHeader__timeline"> <div class="articleHeader__timeline_item "> <strong>收到了</年代trong> <span>05年7月2011年</年代p一个n> </div> <div class="articleHeader__timeline_item "> <strong>修改后的</年代trong> <span>2011年9月30日</年代p一个n> </div> <div class="articleHeader__timeline_item "> <strong>接受</年代trong> <span>2011年10月02</年代p一个n> </div> <div class="articleHeader__timeline_item articleHeader__timeline_item_sticky"> <strong>发表</年代trong> <span>2012年1月17日</年代p一个n> </div> </div> </div> <div class="articleBody"> <div class="xml-content"> <h4 class="header" id="abstract">文摘</h4> <p>被动免疫抗体的重组<我>恶性疟原虫</我>P0 riboprotein (rPfP0, 61 - 316个氨基酸)提供了防止疟疾。Carboxy-terminal 16个氨基酸的蛋白质(PfP0C0)是守恒的,显示69%的人类和小鼠P0身份。抗体这一领域中发现10 - 15%的系统性红斑狼疮患者。我们对体液反应的本质与rPfP0 PfP0C0通过多次免疫小鼠。我们未能提高稳定anti-PfP0C0杂种细胞从任何的21个老鼠。平均血清anti-PfP0C0效价仍低(<年代vg height="15.3375" id="M1" style="vertical-align:-1.09097pt;width:95.525002px;" version="1.1" viewbox="0 0 95.525002 15.3375" width="95.525002" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,15.3375)"> <g transform="translate(72,-59.73)"> <text transform="matrix(1,0,0,-1,-71.95,60.86)"> <tspan style="font-size: 12.50px; " x="0" y="0"> 5</t年代p一个n> <tspan style="font-size: 12.50px; " x="6.2515001" y="0"> 。</t年代p一个n> <tspan style="font-size: 12.50px; " x="9.3772497" y="0"> 1</t年代p一个n> <tspan style="font-size: 12.50px; " x="18.404415" y="0"> ±</t年代p一个n> <tspan style="font-size: 12.50px; " x="29.744637" y="0"> 1</t年代p一个n> <tspan style="font-size: 12.50px; " x="35.996136" y="0"> 。</t年代p一个n> <tspan style="font-size: 12.50px; " x="39.121887" y="0"> 3</t年代p一个n> <tspan style="font-size: 12.50px; " x="48.149052" y="0"> ×</t年代p一个n> <tspan style="font-size: 12.50px; " x="58.92664" y="0"> 1</t年代p一个n> <tspan style="font-size: 12.50px; " x="65.178139" y="0"> 0</t年代p一个n> </text> <text transform="matrix(1,0,0,-1,-0.51,66.03)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 4</t年代p一个n> </text> </g> </g> </svg>)。病理变化观察七增强后的老鼠。吸附与dinitrophenyl半抗原显示主要polyreactive anti-PfP0C0反应。这个polyreactivity分布在所有的同形像。类似polyreactive应对PfP0和PfP0C0观察疟疾患者的血清。我们的数据表明,PfP0诱发异常体液反应,这可能导致寄生虫的免疫逃避机制。</p> <span class="end-abs"></span> <h4 id="introduction">1。介绍</h4> <p>核糖体磷蛋白质P0中性是一个高度保守的蛋白质在60年代的真核生物核糖体亚基(<一个href="#B1">1</一个>]。P0,连同相关的酸性核糖体磷蛋白质P1和P2,形成pentameric蛋白质复合体(P1)<年代ub>2</年代ub>p0 - (P2)<年代ub>2</年代ub>有一个角色在组装GTPase-binding网站的大亚基的核糖体(<一个href="#B2">2</一个>- - - - - -<一个href="#B4">4</一个>]。P0是至关重要的细胞生存敲出来是致命的<我>酿酒酵母</我>和<我>鼠体内</我>(<一个href="#B5">5</一个>,<一个href="#B100">6</一个>]。它被假定有多个其他功能包括apurinic-apyrimidinic酶活动<我>黑腹果蝇</我>(<一个href="#B6">7</一个>),调节基因表达<我>果蝇</我>在人类中,细胞凋亡和致癌作用[<一个href="#B6">7</一个>- - - - - -<一个href="#B9">10</一个>]。P0已被证明是表面上的<我>疟原虫spp,刚地弓形虫</我>,<我>酿酒酵母</我>(<一个href="#B10">11</一个>)以及表面上的神经,肝和其他细胞系(<一个href="#B11">12</一个>,<一个href="#B12">13</一个>]。人类P蛋白已经被广泛的研究,因为它们与系统性红斑狼疮(SLE),一种自身免疫性疾病。大约10 - 15%的病人患有系统性红斑狼疮拥有自身抗体对守恒16 carboxy-terminal氨基酸(<一个href="#B13">14</一个>]。Clustal分析表明,这一地区的蛋白在不同物种高度保守的<一个href="#B14">15</一个>]。人类和小鼠P0,例如,仅在六个不同氨基酸和狼疮域(图是相同的<一个href="//www.newsama.com/journals/bmri/2012/695843/fig1/" target="_blank">1</一个>)。我们曾表明,87%的成年居民高传播疟疾地区的印度东部拥有抗体<我>恶性疟原虫</我>P0 (PfP0) [<一个href="#B15">16</一个>]。同样,60%的成年人居住在肯尼亚显示大量的t细胞反应PfP0蛋白(<一个href="#B16">17</一个>]。多克隆和单克隆抗体PfP0已被证明阻止疟原虫入侵红细胞<我>在体外</我>和<我>在活的有机体内</我>(<一个href="#B14">15</一个>,<一个href="#B17">18</一个>,<一个href="#B18">19</一个>]。当我们试图提高单克隆抗体(mab)对主要的PfP0片段,重组PfP0 (rPfP0 61−316个氨基酸),我们发现第一个鼠标,收到7注射(4周,3月),导致了不稳定的杂种细胞对氨基酸的蛋白质。第二只老鼠收到9注射蛋白质(4周,5月),引发了几个独立的马伯克隆,其中大部分是专门应对极端carboxy-terminal PfP0C0(300−316氨基酸,图<一个href="//www.newsama.com/journals/bmri/2012/695843/fig1/" target="_blank">1</一个>)[<一个href="#B18">19</一个>]。这个鼠标的血清反应只与rPfP0 PfP0C0,但不承认其他重叠肽来源于蛋白质(<一个href="#B200">20.</一个>]。向人类P0 carboxy-terminal PfP0C0显示,69%身份。这种优势的抗体对红斑狼疮域可能是由于老鼠的年龄(8个月),因为故障重复免疫接种后免疫耐受,或两者兼而有之。或者,它可能是一个特殊的老鼠的反应。</p> <div class="partial-carousel-wrapper"> <div class="floats-partial-section"> <div class="floats-partial-content"> <div class="partial-carousel--full-image partial-carousel-59f726cbd1f28af5905a12c8c7051bb7"> <div class="partial-carousel--single-image"> <img loading="lazy" alt="" src="https://static.hindawi.com/articles/bmri/volume-2012/695843/figures/695843.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-59f726cbd1f28af5905a12c8c7051bb7 partial-carousel-thumbnail"> <button aria-label="Slide to " class="partial-carousel-dot"><img loading="lazy" alt="" src="https://static.hindawi.com/articles/bmri/volume-2012/695843/thumbnails/695843.fig.001_th.jpg"><br><strong></strong></button> </div> </div> <div class="floats-partial-middle--nav"> <div class="partial-carousel-next-prev-59f726cbd1f28af5905a12c8c7051bb7 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p一个n> <a aria-label="View full page" class="caption-partial-url" href="//www.newsama.com/journals/bmri/2012/695843/fig1/" title="" target="_blank"></a> </div> <div class="floats-partial-caption-text"> <table> <tbody> <tr> <td>PfP0示意图表示,重组PfP0, PfP0C0 P0多重序列比对。</td> </tr> </tbody> </table> </div> </div> </div> </div> <p>PfP0自anti-PfP0抗体是一个潜在的候选疫苗被证明防止疟疾感染小鼠模型(<一个href="#B17">18</一个>,<一个href="#B18">19</一个>]。因为它的守恒性质和carboxy-terminal域对人类的同源蛋白质,它也可能表现得像一个自身抗原。确定很重要的质量和数量引起的体液反应重复免疫接种后的蛋白质。因此,我们进行了这个系统的研究中,我们试图提高对PfP0C0马伯rPfP0多次免疫接种。中央和周边水平选择流程管理B细胞的生存能力对一个特定的免疫原,而外围抗原驱动选择流程确定体液反应的类型和程度。我们推断,如果脾B细胞的反映整个B细胞反应和B细胞特异性不偏见混合形成,然后形成杂种细胞的频率应该反映PfP0不同抗原表位的免疫原性。我们还研究了血清anti-PfP0C0反应的本质。</p> <p>我们未能提高单个anti-PfP0C0杂种细胞从任何的21个老鼠用于这些后续的实验,表明第一次成功地提高杂种细胞对PfP0C0域可能是由于一个不寻常的反应中观察到,一个鼠标(结合23两项研究中使用的老鼠)。我们观察到结缔组织纤维化脾脏的免疫接种程序的第四个月,逐渐的增加与进一步的免疫接种。尸检显示病变的肝脏、心脏、肾脏和肺的老鼠。平均血清anti-PfP0C0滴定度保持低(<年代vg height="15.3375" id="M2" style="vertical-align:-1.09097pt;width:95.525002px;" version="1.1" viewbox="0 0 95.525002 15.3375" width="95.525002" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,15.3375)"> <g transform="translate(72,-59.73)"> <text transform="matrix(1,0,0,-1,-71.95,60.86)"> <tspan style="font-size: 12.50px; " x="0" y="0"> 5</t年代p一个n> <tspan style="font-size: 12.50px; " x="6.2515001" y="0"> 。</t年代p一个n> <tspan style="font-size: 12.50px; " x="9.3772497" y="0"> 1</t年代p一个n> <tspan style="font-size: 12.50px; " x="18.404415" y="0"> ±</t年代p一个n> <tspan style="font-size: 12.50px; " x="29.744637" y="0"> 1</t年代p一个n> <tspan style="font-size: 12.50px; " x="35.996136" y="0"> 。</t年代p一个n> <tspan style="font-size: 12.50px; " x="39.121887" y="0"> 3</t年代p一个n> <tspan style="font-size: 12.50px; " x="48.149052" y="0"> ×</t年代p一个n> <tspan style="font-size: 12.50px; " x="58.92664" y="0"> 1</t年代p一个n> <tspan style="font-size: 12.50px; " x="65.178139" y="0"> 0</t年代p一个n> </text> <text transform="matrix(1,0,0,-1,-0.51,66.03)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 4</t年代p一个n> </text> </g> </g> </svg>)即使10助推器。Dinitrophenyl (DNP)吸附研究表明,很大程度上是polyreactive体液反应。这polyreactivity并不局限于任何特定的免疫球蛋白同形像,而是分布在所有同形像。序列分析的七个杂种细胞获得最初的研究显示,他们来自一个克隆。我们从简单的疟疾病人血清分析确定蛋白质polyreactivity的程度。我们分析发现一个类似polyreactive应对PfP0和PfP0C0在这些血清抗原决定基。我们的数据表明,PfP0诱发小鼠的体液反应。感应的越轨,low-titre polyreactive反应可能逃避宿主的免疫系统的一种方法。</p> <h4 id="materials-and-methods">2。材料和方法</h4> <h5 id="sec2.1">2.1。老鼠</h5> <p>六个雌性Balb /<我>c</我>老鼠从当地的动物育种获得设备的塔塔理工学院基础研究,孟买,印度。老鼠在特定的无菌条件下培育和维护。所有的实验研究是根据建议进行CPCSEA(委员会控制和监督的目的动物实验)。</p> <h5 id="sec2.2">2.2。免疫接种和建立杂种细胞</h5> <p>免疫原和肽:表达和纯化的重组PfP0(氨基酸61−316)作为GST融合蛋白做了如前所述[<一个href="#B19">21</一个>]。的重组<我>大肠杆菌</我>细胞包含<我>PfP0</我>出了基因片段2 h在37°C,用IPTG诱导,收割,细胞溶解。细胞溶解产物离心机,包含融合蛋白和不溶性微粒分数是决定SDS-polyacrylamide制备凝胶。一条重组蛋白的凝胶对应MW切除,electroeluted,对PBS分离,集中。的身份证实了蛋白质免疫印迹分析描述(<一个href="#B20">22</一个>]。蚁脑匀浆,<我>恶性疟原虫</我>磷酸果糖激酶,<我>恶性疟原虫</我>烯醇酶准备描述(<一个href="#B21">23</一个>- - - - - -<一个href="#B23">25</一个>]。P0蛋白质<我>刚地弓形虫</我>(TgP0)在pGEX4T1克隆和表达GST融合蛋白。重组,全身的销售税−TgP0提取使用sarkosyl[从诱导细胞颗粒<一个href="#B24">26</一个>),纯化使用谷胱甘肽琼脂糖珠从溶解产物(通用电气医疗集团),与PBS包含150毫米生理盐水冲洗三次,并使用100毫米谷胱甘肽筛选了。蛋白质的身份被确认使用sds - page和免疫印迹(数据未显示)牛血清白蛋白耦合PfP0C0 (BSA-PfP0C0)准备如前所述<一个href="#B18">19</一个>]。</p> <p>合成肽MoP0C0 (EESEESDEDMGFGLFD) PfP0C0 (EEEEEEDGFMGFGMFD)获得Mimotopes,堪培拉,澳大利亚。牛胰岛素,ssDNA, dsDNA从σ(圣路易斯,密苏里州,美国)。</p> <p>免疫和杂种细胞建立是描述Rajeshwari et al ., 2004<一个href="#B18">19</一个>]。简单地说,50<我>μ</我>gs的蛋白质在弗氏佐剂乳化在小鼠腹腔接种。动物收到四个每周注射之后,每月注射。除了第一个用弗氏完全佐剂免疫,免疫接种工作的其他弗氏不完全佐剂。4天在融合之前,250年的老鼠了<我>μ</我>克盐水的免疫原。老鼠牺牲每个每月注射后,血清收集,脾脏被收获,脾细胞与小鼠骨髓瘤Sp2/0细胞融合。Antibody-secreting克隆选择通过ELISA (<一个href="#B25">27</一个>]。Immunogen-recognizing杂种细胞被subcloned monoclonality通过限制稀释。rPfP0免疫,老鼠放弃7月免疫接种;三个老鼠牺牲后每个月免疫。</p> <h5 id="sec2.3">2.3。人类血清样本</h5> <p>血清样本收集从简单的疟疾病人以及免疫成年人生活在高度流行区在奥里萨邦,印度。存在与否<我>恶性疟原虫</我>感染是由显微镜检查确认Giemsa-stained厚薄血液涂片或通过使用商业套装。知情同意后收集到的样本,从道德委员会获得必要的许可后,渣打银行医学院和医院,Cuttack、印度。</p> <h5 id="sec2.4">2.4。ELISA</h5> <p>抗体反应是由ELISA (<一个href="#B18">19</一个>]。短暂,Maxisorp板块(Nunc、鲁开德、丹麦)涂在一夜之间在4°C全抗原(5<我>μ</我>g / mL)或合成肽(200 ng / mL)在PBS, pH值7.2。盘子被封锁的1% BSA之前添加杂种细胞上清液或适当的稀释血清,用兔子anti-mouse Ig共轭开发辣根过氧化物酶(勃林格曼海姆,曼海姆,德国)和abt(勃林格曼海姆),和吸光度(光密度;OD)为405 nm EL808超微型板块读者(美国Biotek仪器公司、Winooski VT)。</p> <p>探测polyreactivity DNP是共轭CNBr-activated琼脂糖珠(通用电气医疗集团,小都,白金汉郡,英国)按照制造商的指示。简而言之,2,4-DNP -<我>ε</我>赖氨酸(σ)溶解在0.1 M NaHCO3 pH值8.3包含0.5 M氯化钠,加入琼脂糖珠在1毫米HCl肿胀,和孵化立式圆筒形混合器在室温下1 h。洗掉多余的配体后,活跃的网站被封锁使用0.1米Tris-HCl缓冲区,pH值8.0。的珠子用三周期0.1乙酸/醋酸钠,pH值4.0包含0.5 M氯化钠,后跟一个用0.1 Tris-HCl, pH值8包含0.5 M氯化钠。整除的血清稀释与否与孵化DNP-sepharose珠子章动器和离心机为1.5小时。上层清液稀释进一步用于ELISA。polyreactivity百分比计算下:<年代p一个ncl一个年代年代="equation" id="eq1"> <svg height="57.950001" id="M3" preserveaspectratio="xMaxYMin" style="vertical-align:-0pt;width:700.9375px;" version="1.1" viewbox="0 0 700.9375 57.950001" width="700.9375" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,57.95)"> <g transform="translate(72,-25.64)"> <text transform="matrix(1,0,0,-1,51.43,63.12)"> <tspan style="font-size: 12.50px; " x="3.47" y="28.51"> =</t年代p一个n> <tspan style="font-size: 12.50px; " x="0" y="0"> %</t年代p一个n> <tspan style="font-size: 12.50px; " x="13.50324" y="0"> p</t年代p一个n> <tspan style="font-size: 12.50px; " x="19.75474" y="0"> o</t年代p一个n> <tspan style="font-size: 12.50px; " x="26.006241" y="0"> l</t年代p一个n> <tspan style="font-size: 12.50px; " x="29.232014" y="0"> y</t年代p一个n> <tspan style="font-size: 12.50px; " x="35.483513" y="0"> r</t年代p一个n> <tspan style="font-size: 12.50px; " x="39.622005" y="0"> e</t年代p一个n> <tspan style="font-size: 12.50px; " x="45.17334" y="0"> 一个</t年代p一个n> <tspan style="font-size: 12.50px; " x="50.72467" y="0"> c</t年代p一个n> <tspan style="font-size: 12.50px; " x="56.276005" y="0"> t</t年代p一个n> <tspan style="font-size: 12.50px; " x="59.751839" y="0"> 我</t年代p一个n> <tspan style="font-size: 12.50px; " x="63.227673" y="0"> v</t年代p一个n> <tspan style="font-size: 12.50px; " x="69.479172" y="0"> 我</t年代p一个n> <tspan style="font-size: 12.50px; " x="72.955002" y="0"> t</t年代p一个n> <tspan style="font-size: 12.50px; " x="76.43084" y="0"> y</t年代p一个n> <tspan style="font-size: 12.50px; " x="16.700001" y="21.25"> O</t年代p一个n> <tspan style="font-size: 12.50px; " x="25.727165" y="21.25"> D</t年代p一个n> <tspan style="font-size: 12.50px; " x="38.917831" y="21.25"> o</t年代p一个n> <tspan style="font-size: 12.50px; " x="45.169331" y="21.25"> f</t年代p一个n> <tspan style="font-size: 12.50px; " x="53.49633" y="21.25"> u</t年代p一个n> <tspan style="font-size: 12.50px; " x="59.747829" y="21.25"> n</t年代p一个n> <tspan style="font-size: 12.50px; " x="65.999329" y="21.25"> 一个</t年代p一个n> <tspan style="font-size: 12.50px; " x="71.550659" y="21.25"> d</t年代p一个n> <tspan style="font-size: 12.50px; " x="77.802162" y="21.25"> 年代</t年代p一个n> <tspan style="font-size: 12.50px; " x="82.665825" y="21.25"> o</t年代p一个n> <tspan style="font-size: 12.50px; " x="88.917328" y="21.25"> r</t年代p一个n> <tspan style="font-size: 12.50px; " x="93.080826" y="21.25"> b</t年代p一个n> <tspan style="font-size: 12.50px; " x="99.332329" y="21.25"> e</t年代p一个n> <tspan style="font-size: 12.50px; " x="104.88366" y="21.25"> d</t年代p一个n> <tspan style="font-size: 12.50px; " x="115.31116" y="21.25"> 年代</t年代p一个n> <tspan style="font-size: 12.50px; " x="120.17483" y="21.25"> e</t年代p一个n> <tspan style="font-size: 12.50px; " x="125.72616" y="21.25"> r</t年代p一个n> <tspan style="font-size: 12.50px; " x="130.18973" y="21.25"> u</t年代p一个n> <tspan style="font-size: 12.50px; " x="136.44124" y="21.25"> 米</t年代p一个n> <tspan style="font-size: 12.50px; " x="148.94423" y="21.25"> −</t年代p一个n> <tspan style="font-size: 12.50px; " x="160.28445" y="21.25"> O</t年代p一个n> <tspan style="font-size: 12.50px; " x="169.31161" y="21.25"> D</t年代p一个n> <tspan style="font-size: 12.50px; " x="182.50229" y="21.25"> o</t年代p一个n> <tspan style="font-size: 12.50px; " x="188.75378" y="21.25"> f</t年代p一个n> <tspan style="font-size: 12.50px; " x="197.09328" y="21.25"> 一个</t年代p一个n> <tspan style="font-size: 12.50px; " x="202.64462" y="21.25"> d</t年代p一个n> <tspan style="font-size: 12.50px; " x="208.89612" y="21.25"> 年代</t年代p一个n> <tspan style="font-size: 12.50px; " x="213.75978" y="21.25"> o</t年代p一个n> <tspan style="font-size: 12.50px; " x="220.01128" y="21.25"> r</t年代p一个n> <tspan style="font-size: 12.50px; " x="224.17479" y="21.25"> b</t年代p一个n> <tspan style="font-size: 12.50px; " x="230.42628" y="21.25"> e</t年代p一个n> <tspan style="font-size: 12.50px; " x="235.97762" y="21.25"> d</t年代p一个n> <tspan style="font-size: 12.50px; " x="246.39261" y="21.25"> 年代</t年代p一个n> <tspan style="font-size: 12.50px; " x="251.25629" y="21.25"> e</t年代p一个n> <tspan style="font-size: 12.50px; " x="256.80762" y="21.25"> r</t年代p一个n> <tspan style="font-size: 12.50px; " x="261.27118" y="21.25"> u</t年代p一个n> <tspan style="font-size: 12.50px; " x="267.52267" y="21.25"> 米</t年代p一个n> </text> <g> <path d="m 68.13,37.74 260.56,0" 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,-1,133.68,25.86)"> <tspan style="font-size: 12.50px; " x="0" y="0"> O</t年代p一个n> <tspan style="font-size: 12.50px; " x="9.0271664" y="0"> D</t年代p一个n> <tspan style="font-size: 12.50px; " x="22.217831" y="0"> o</t年代p一个n> <tspan style="font-size: 12.50px; " x="28.469332" y="0"> f</t年代p一个n> <tspan style="font-size: 12.50px; " x="36.796329" y="0"> u</t年代p一个n> <tspan style="font-size: 12.50px; " x="43.047829" y="0"> n</t年代p一个n> <tspan style="font-size: 12.50px; " x="49.299328" y="0"> 一个</t年代p一个n> <tspan style="font-size: 12.50px; " x="54.850662" y="0"> d</t年代p一个n> <tspan style="font-size: 12.50px; " x="61.102161" y="0"> 年代</t年代p一个n> <tspan style="font-size: 12.50px; " x="65.965828" y="0"> o</t年代p一个n> <tspan style="font-size: 12.50px; " x="72.217331" y="0"> r</t年代p一个n> <tspan style="font-size: 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x="344.60349" y="-19.83"> 1</t年代p一个n> <tspan style="font-size: 12.50px; " x="350.85501" y="-19.83"> )</t年代p一个n> </text> </g> </g> </svg></span></p> <h5 id="sec2.5">2.5。测定RNA序列Anti-PfP0C0马伯克隆</h5> <p>Anti-PfP0C0抗体生产杂种细胞克隆(1 a4, b3、2 c11、1 e5f4 1 f6, 2 g1和2 h1)细胞溶解在试剂盒(美国表达载体,卡尔斯巴德,CA)和RNA制备根据制造商的协议。RNA的互补脱氧核糖核酸制备使用3′底漆(重或轻链恒定底漆)和MMLV逆转录酶(内)。PCR扩增的轻、重链进行使用引物中描述表<一个href="//www.newsama.com/journals/bmri/2012/695843/tab1/" target="_blank">1</一个>。用来放大PCR片段如下条件:DNA融化在91°C 1分钟,2分钟引物退火52°C,聚合酶扩展在72°C 1.5分钟30周期进行。PCR克隆产品TA pGEM-T向量系统(WI Promega,麦迪逊,美国),和结扎混合变换XL-1蓝色<我>大肠杆菌</我>细菌。阳性克隆测序使用M13F (5′d [GTAAAACGACGGCCAG] 3′)和M13R (5′d [CAGGAAACAGCTATGAC] 3′)引物。</p> <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p一个n> <a aria-label="View full page" class="caption-partial-url" href="//www.newsama.com/journals/bmri/2012/695843/tab1/" title="" target="_blank"></a> </div> <div class="floats-partial-caption-text"> 引物用于增强抗体可变区。</d我v> <a class="table-thumb-overlay" href="//www.newsama.com/journals/bmri/2012/695843/tab1" target="_blank" aria-label="View full page"></a> </div> </div> <h5 id="sec2.6">2.6。统计分析</h5> <p>成对Wilcoxan符号秩检验是用来比较和评价的统计意义unadsorbed和小鼠血清吸附OD。非参数Mann-Whitney测试是用来评估人类血清数据的统计学意义。GraphPad Instat软件被用于分析。</p> <h4 id="results-and-discussion">3所示。结果与讨论</h4> <h5 id="sec3.1">3.1。重组PfP0免疫接种失败的产量稳定Anti-PfP0C0马伯生产杂种细胞</h5> <p>我们有兴趣提高马伯重组<我>恶性疟原虫</我>核糖体蛋白P0 (PfP0)多克隆抗体这种蛋白质有抑制疟原虫入侵红细胞(<一个href="#B14">15</一个>,<一个href="#B18">19</一个>]。在先前的研究中,我们成功地提高稳定马伯反对PfP0经过多次免疫只在一个鼠标,和大多数的人反对PfP0C0 [<一个href="#B18">19</一个>]。极端的c端域以来人类P0蛋白质同源PfP0羧基端(PfP0C0;300−316个氨基酸),是主要的p蛋白质自身抗原参与红斑狼疮(<一个href="#B13">14</一个>),我们有兴趣探索的性质PfP0C0体液反应,想要确定我们会获得马伯的频率对这个领域PfP0蛋白质。全长蛋白显示了极其可怜的表达式,因此我们使用了大片段的蛋白质(rPfP0 61−316个氨基酸)免疫接种。</p> <p>我们6免疫Balb /<我>c</我>小鼠4周注射rPfP0弗氏完全佐剂,紧随其后的是每月的助推器。小鼠脾脏从3每个月注射后收获杂种细胞的准备(5日到11日免疫)的。表<一个href="//www.newsama.com/journals/bmri/2012/695843/tab2/" target="_blank">2</一个>,显示结果为5日,7日,9日和11日免疫。类似的结果剩下的时间点。从表<一个href="//www.newsama.com/journals/bmri/2012/695843/tab2/" target="_blank">2</一个>,我们未能获得任何稳定的克隆对PfP0C0,尽管一再免疫接种或老鼠的年龄。克隆筛选约1800只取得了22个稳定的克隆。大多数克隆polyreactive或停止抗体生产几天之内,未能认识到carboxy-terminal抗原决定基。因此,无论是动物的年龄还是重复与潜在的自身抗原免疫接种可以成功的原因提高杂种细胞的初步研究。</p> <div class="floats-partial-section partial-other-wrapper" data-section="tab2"> <div class="floats-partial-footer"> <div class="floats-partial-caption"> <span class="caption-text">表2</年代p一个n> <a aria-label="View full page" class="caption-partial-url" href="//www.newsama.com/journals/bmri/2012/695843/tab2/" title="" target="_blank"></a> </div> <div class="floats-partial-caption-text"> 后血清滴定度和杂种细胞获得重复免疫与各种蛋白质。</d我v> <a class="table-thumb-overlay" href="//www.newsama.com/journals/bmri/2012/695843/tab2" target="_blank" aria-label="View full page"></a> </div> </div> <p>我们无法提高稳定的杂种细胞对PfP0C0不能归咎于错误的技术,因为我们成功获得多个稳定的克隆对多种蛋白质(表<一个href="//www.newsama.com/journals/bmri/2012/695843/tab2/" target="_blank">2</一个>)。这些包括蚁脑匀浆,<我>果蝇</我>用鼠标translin熊52%同源性蛋白(<一个href="#B26">28</一个>),寄生虫蛋白质等<我>恶性疟原虫</我>果糖激酶,<我>β</我>和潜在autoantigenic蛋白质等<我>恶性疟原虫</我>烯醇酶(<一个href="#B27">29日</一个>,<一个href="#B28">30.</一个>)和TgP0。PfP0的身份和鼠标P0糖基在极端的16个氨基酸是69%(图<一个href="//www.newsama.com/journals/bmri/2012/695843/fig1/" target="_blank">1</一个>)。这同源PfP0鼠标P0独自不能缺乏杂种细胞的唯一原因,因为<我>恶性疟原虫</我>烯醇酶和TgP0显示相当大的同源性与鼠标烯醇酶和鼠标P0(75%和62.5%,分别地。),而这些都服从一代杂种细胞大量的稳定。二次抗原挑战导致代长寿的浆细胞能够分泌高亲和性抗体免疫抗原(<一个href="#B29">31日</一个>]。人们很容易推测PfP0是一个不寻常的抗原,它未能引起一个健壮的B细胞反应,因为重复免疫产生稳定的杂种细胞很少,而且都不是针对抗原的免疫原性羧基端。</p> <h5 id="sec3.2">3.2。马伯早些时候提出反对PfP0C0源自一个B细胞克隆</h5> <p>以来在我们先前的研究获得几个马伯专门针对PfP0C0从一个鼠标,我们分析了七个马伯的同形像和序列(1 a4, b3、2 c11、1 e5f4 1 f6, 2 g1和2 h1)从这个研究建立他们的亲缘早些时候,如果任何。同形像统计图分析表明,所有的马伯属于IgG1同形像。我们进行rt - pcr和放大产品的重型和轻型链这七个马伯克隆并测序(图<一个href="//www.newsama.com/journals/bmri/2012/695843/fig2/" target="_blank">2</一个>)。观察到,CDR2和CDR3上区域是一样的重链的所有七个克隆。CDR1地区的两个单基地变化1 a4和1 e5f4和3基础2 c11变化催生了一些氨基酸变化的CDR1地区3 7克隆。对于轻链,1 a4和2 c11显示某些基础的变化,而其他五克隆都是相同的。虽然1 a4 CDR3上地区是明显不同的,附近的CDR1和2区域相同。其余地区的IgG1链这些克隆是相同的(数据未显示)。因此,明显在前面获得的克隆研究起源于一个B细胞克隆。这可能是由于一个不寻常的克隆扩张,可能由于公差分解,绝对是一个异常的发病率因为后续分析未能重现我们早些时候获得对PfP0C0马伯克隆(表的结果<一个href="//www.newsama.com/journals/bmri/2012/695843/tab2/" target="_blank">2</一个>)。</p> <div class="partial-carousel-wrapper"> <div class="floats-partial-section"> <div class="floats-partial-content"> <div class="partial-carousel--full-image partial-carousel-1a7cfdda509238984b71e6cee3692d8c"> <div class="partial-carousel--single-image"> <img loading="lazy" alt="" src="https://static.hindawi.com/articles/bmri/volume-2012/695843/figures/695843.fig.002.jpg"> <br> <strong></strong> </div> </div> </div> <div class="floats-partial-middle"> <div class="floats-partial-middle--thumbs"> <div class="partial-carousel-dots-1a7cfdda509238984b71e6cee3692d8c partial-carousel-thumbnail"> <button aria-label="Slide to " class="partial-carousel-dot"><img loading="lazy" alt="" src="https://static.hindawi.com/articles/bmri/volume-2012/695843/thumbnails/695843.fig.002_th.jpg"><br><strong></strong></button> </div> </div> <div class="floats-partial-middle--nav"> <div class="partial-carousel-next-prev-1a7cfdda509238984b71e6cee3692d8c 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p一个n> <a aria-label="View full page" class="caption-partial-url" href="//www.newsama.com/journals/bmri/2012/695843/fig2/" title="" target="_blank"></a> </div> <div class="floats-partial-caption-text"> <table> <tbody> <tr> <td>序列测定anti-PfP0C0马伯在第一项研究中获得的。七马伯获得(在我们的早期研究<一个href="https://static.hindawi.com/articles/bmri/volume-2012/695843/figures/695843/">19</一个>),即1 a4, b3, 2 c11 1 e5f4 1 f6, 2 g1和2 h1测序以确定他们的亲缘。除了一些微小的变化,(红色),所有七马伯都几乎相同,这表明他们已经出现从一个B细胞克隆。</td> </tr> </tbody> </table> </div> </div> </div> </div> <h5 id="sec3.3">3.3。重组PfP0免疫导致小鼠的病理变化</h5> <p>脾收获杂种细胞代过程中,我们注意到轻微的结缔组织纤维化的脾脏免疫(表7<一个href="//www.newsama.com/journals/bmri/2012/695843/tab2/" target="_blank">2</一个>)。加强免疫后的动物开始生病。这逐渐纤维化恶化,11日免疫脾变得很难收获(图<一个href="//www.newsama.com/journals/bmri/2012/695843/fig3/" target="_blank">3</一个>)。明显的脾纤维化早期的研究没有观察到。以来,研究的目的是为了获得PfP0C0马伯,尸检病理检查也没有进行。后期分析的老鼠显示病变的所有主要器官如心脏、肺、肝脏和肾脏(表<一个href="//www.newsama.com/journals/bmri/2012/695843/tab3/" target="_blank">3</一个>)。有趣的是,大脑中没有发现异常。这些研究结果表明,重复与rPfP0导致体液免疫自身免疫反应,可能是因为之间的同源性寄生虫P0 P0和老鼠。大脑是分离血液通过血脑屏障。抗体通常不会跨越这一障碍(<一个href="#B30">32</一个>]。所有主要器官的病理变化观察排除大脑提出自身抗体可能造成的伤害。因此,我们调查了血清对PfP0C0搞笑回应。</p> <div class="floats-partial-section partial-other-wrapper" data-section="tab3"> <div class="floats-partial-footer"> <div class="floats-partial-caption"> <span class="caption-text">表3</年代p一个n> <a aria-label="View full page" class="caption-partial-url" href="//www.newsama.com/journals/bmri/2012/695843/tab3/" title="" target="_blank"></a> </div> <div class="floats-partial-caption-text"> 组织病理学结果调查重复PfP0政府重组后的老鼠。</d我v> <a class="table-thumb-overlay" href="//www.newsama.com/journals/bmri/2012/695843/tab3" target="_blank" aria-label="View full page"></a> </div> </div> <div class="partial-carousel-wrapper"> <div class="floats-partial-section"> <div class="floats-partial-content"> <div class="partial-carousel--full-image partial-carousel-2ad62dfe75e8b2c2d2fb060d50d9386e"> <div class="partial-carousel--single-image"> <img loading="lazy" alt="(一)" src="https://static.hindawi.com/articles/bmri/volume-2012/695843/figures/695843.fig.003a.jpg"> <br> <strong>(一)</年代trong> </div> <div class="partial-carousel--single-image"> <img loading="lazy" alt="(b)" src="https://static.hindawi.com/articles/bmri/volume-2012/695843/figures/695843.fig.003b.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-2ad62dfe75e8b2c2d2fb060d50d9386e partial-carousel-thumbnail"> <button aria-label="Slide to (a) " class="partial-carousel-dot"><img loading="lazy" alt="(一)" src="https://static.hindawi.com/articles/bmri/volume-2012/695843/thumbnails/695843.fig.003a_th.jpg"><br><strong>(一)</年代trong></button> <button aria-label="Slide to (b) " class="partial-carousel-dot"><img loading="lazy" alt="(b)" src="https://static.hindawi.com/articles/bmri/volume-2012/695843/thumbnails/695843.fig.003b_th.jpg"><br><strong>(b)</年代trong></button> </div> </div> <div class="floats-partial-middle--nav"> <div class="partial-carousel-next-prev-2ad62dfe75e8b2c2d2fb060d50d9386e 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p一个n> <a aria-label="View full page" class="caption-partial-url" href="//www.newsama.com/journals/bmri/2012/695843/fig3/" title="" target="_blank"></a> </div> <div class="floats-partial-caption-text"> <table> <tbody> <tr> <td>脾纤维化与重组PfP0重复免疫接种后观察。(一)控制小鼠脾脏。(b)脾鼠标后重复接种重组PfP0(4周和7个月)。箭头指向脾脏。注意减少脾脏的大小和纤维化。组织病理学分析显示的淋巴细胞和脾的广泛替代组织和结缔组织。</td> </tr> </tbody> </table> </div> </div> </div> </div> <h5 id="sec3.4">3.4。重组PfP0诱发Low-Titre,主要Polyreactive血清Anti-PfP0C0响应</h5> <p>从每个月免疫后小鼠血清收集rPfP0 anti-PfP0C0响应进行了测试。血清滴定度保持低蛋白(即使在11日管理表<一个href="//www.newsama.com/journals/bmri/2012/695843/tab2/" target="_blank">2</一个>)。相比之下,high-titre反应得到4或5免疫接种后对各种蛋白质,包括那些显示高度的同源蛋白质如老鼠<我>恶性疟原虫</我>烯醇酶,<我>果蝇</我>translin, TgP0。滴定度较低的血清,再加上不稳定polyreactive杂种细胞,建议诱导anti-PfP0C0反应是polyreactive的可能性。Polyreactive抗体较低亲和力抗体可以结合各种生物分子的自我和non-self-origin [<一个href="#B31">33</一个>,<一个href="#B32">34</一个>]。他们是正常血清成分和最初的免疫反应的重要组成部分。DNP治疗是常用的去除polyreactive抗体在动物不暴露在半抗原(<一个href="#B33">35</一个>,<一个href="#B34">36</一个>]。我们治疗血清DNP-sepharose珠子和确定anti-PfP0C0滴定度的吸附和unadsorbed血清ELISA。DNP导致治疗显著降低anti-PfP0C0血清的反应,表明PfP0免疫诱导很大程度上polyreactive anti-PfP0C0响应。图<一个href="//www.newsama.com/journals/bmri/2012/695843/fig4/" target="_blank">4(一)</一个>显示了一个典型的反应DNP吸附和unadsorbed血清样本。polyreactivity的程度仍然很高(中值32%)即使重复助推器(图<一个href="//www.newsama.com/journals/bmri/2012/695843/fig4/" target="_blank">4 (b)</一个>)。这种polyreactive反应并不局限于一个特定的同形像,但被发现在所有同形像,因为DNP治疗导致显著减少anti-PfP0C0反应在所有同形像(图<一个href="//www.newsama.com/journals/bmri/2012/695843/fig4/" target="_blank">4 (c)</一个>)。我们还检测了血清反应dsDNA, ssDNA和胰岛素。图<一个href="//www.newsama.com/journals/bmri/2012/695843/fig4/" target="_blank">4 (d)</一个>显示一个血清样本的结果。类似的结果为其他样本(数据未显示)。</p> <div class="partial-carousel-wrapper"> <div class="floats-partial-section"> <div class="floats-partial-content"> <div class="partial-carousel--full-image partial-carousel-133dae356cda499876c8f0f334ef4b08"> <div class="partial-carousel--single-image"> <img loading="lazy" alt="(一)" src="https://static.hindawi.com/articles/bmri/volume-2012/695843/figures/695843.fig.004a.jpg"> <br> <strong>(一)</年代trong> </div> <div class="partial-carousel--single-image"> <img loading="lazy" alt="(b)" src="https://static.hindawi.com/articles/bmri/volume-2012/695843/figures/695843.fig.004b.jpg"> <br> <strong>(b)</年代trong> </div> <div class="partial-carousel--single-image"> <img loading="lazy" alt="(c)" src="https://static.hindawi.com/articles/bmri/volume-2012/695843/figures/695843.fig.004c.jpg"> <br> <strong>(c)</年代trong> </div> <div class="partial-carousel--single-image"> <img loading="lazy" alt="(d)" src="https://static.hindawi.com/articles/bmri/volume-2012/695843/figures/695843.fig.004d.jpg"> <br> <strong>(d)</年代trong> </div> <div class="partial-carousel--single-image"> <img loading="lazy" alt="(e)" src="https://static.hindawi.com/articles/bmri/volume-2012/695843/figures/695843.fig.004e.jpg"> <br> <strong>(e)</年代trong> </div> </div> </div> <div class="floats-partial-middle"> <div class="floats-partial-middle--thumbs"> <div class="partial-carousel-dots-133dae356cda499876c8f0f334ef4b08 partial-carousel-thumbnail"> <button aria-label="Slide to (a) " class="partial-carousel-dot"><img loading="lazy" alt="(一)" src="https://static.hindawi.com/articles/bmri/volume-2012/695843/thumbnails/695843.fig.004a_th.jpg"><br><strong>(一)</年代trong></button> <button aria-label="Slide to (b) " class="partial-carousel-dot"><img loading="lazy" alt="(b)" src="https://static.hindawi.com/articles/bmri/volume-2012/695843/thumbnails/695843.fig.004b_th.jpg"><br><strong>(b)</年代trong></button> <button aria-label="Slide to (c) " class="partial-carousel-dot"><img loading="lazy" alt="(c)" src="https://static.hindawi.com/articles/bmri/volume-2012/695843/thumbnails/695843.fig.004c_th.jpg"><br><strong>(c)</年代trong></button> <button aria-label="Slide to (d) " class="partial-carousel-dot"><img loading="lazy" alt="(d)" src="https://static.hindawi.com/articles/bmri/volume-2012/695843/thumbnails/695843.fig.004d_th.jpg"><br><strong>(d)</年代trong></button> <button aria-label="Slide to (e) " class="partial-carousel-dot"><img loading="lazy" alt="(e)" src="https://static.hindawi.com/articles/bmri/volume-2012/695843/thumbnails/695843.fig.004e_th.jpg"><br><strong>(e)</年代trong></button> </div> </div> <div class="floats-partial-middle--nav"> <div class="partial-carousel-next-prev-133dae356cda499876c8f0f334ef4b08 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p一个n> <a aria-label="View full page" class="caption-partial-url" href="//www.newsama.com/journals/bmri/2012/695843/fig4/" title="" target="_blank"></a> </div> <div class="floats-partial-caption-text"> <table> <tbody> <tr> <td>Polyreactive血清anti-PfP0C0反应诱导后重复与rPfP0但不是BSA-PfP0C0免疫接种。(a)小鼠的血清注射重组PfP0治疗与否与DNP-sepharose珠子。Anti-PfP0C0滴定度治疗前后测定ELISA。代表的例子anti-PfP0C0 DNP的反应吸附(空圈)和unadsorbed(满圈)血清。误差线代表三个读数的SEM。(b)小鼠接种4周和7月rPfP0注射。整除的血清处理DNP-sepharose珠子polyreactive抗体吸附。酒吧图表描述多个免疫后小鼠的血清polyreactivity百分比表示。误差线代表3血清的SEM。(c)箱形图显示第25和第75百分位数,加上中间,胡须显示最小和最大的区别,圆圈代表局外人,ELISA OD反应的DNP unadsorbed (U)和吸附(A)与重组PfP0 21小鼠血清的免疫;<我>μ</我>(IgM),<我>γ</我>1 (IgG1)<我>γ</我>2 (IgG2a),<我>γ</我>2 b (IgG2b),<我>γ</我>3 (IgG3),<我>α</我>(IgA)。获得的显著值成对Wilcoxan符号秩检验表示。(d) Autoreactivity代表血清样本的牛胰岛素(封闭的圆),dsDNA(开环),和ssDNA rPfP0(封闭的三角形)的小鼠免疫。红线代表未接受免疫接种的血清的反应控制在最低稀释(1:1000)。误差线代表三个读数的SEM。与其他血清也获得类似的结果。(e)小鼠接种BSA-PfP0C0,血清治疗与否与DNP-sepharose珠子。Anti-PfP0C0滴定度治疗前后ELISA的决心。代表的例子anti-PfP0C0 DNP的反应吸附(空圈)和unadsorbed(满圈)血清。误差线代表三个读数的SEM。</td> </tr> </tbody> </table> </div> </div> </div> </div> <h5 id="sec3.5">3.5。疟疾感染也会导致Low-Titre,主要Polyreactive血清Anti-PfP0和Anti-PfP0C0响应</h5> <p>我们希望确定简单的疟疾患者的血清也显示出类似的PfP0 polyreactive反应。蛋白质是高度保守的<我>恶性疟原虫</我>。在报告的13株PlasmoDB [<一个href="#B35">37</一个>),DNA序列是相同的除了一个同义突变株(图<一个href="//www.newsama.com/journals/bmri/2012/695843/fig5/" target="_blank">5</一个>)。PfP0也大量表达表面裂殖子(<一个href="#B17">18</一个>]。虽然我们通常看到高架抗体反应PfP0疟疾免疫成人患者相比(<一个href="#B17">18</一个>),我们没有评估polyreactive组件。我们测试了从免疫血清的成年人也为anti-PfP0疟疾患者无并发症和anti-PfP0C0抗体。早些时候在协议与我们的结果,免疫的成年人,而不是病人,显示响应PfP0升高(图<一个href="//www.newsama.com/journals/bmri/2012/695843/fig6/" target="_blank">6(一)</一个>,<年代vg height="11.0625" id="M8" style="vertical-align:-0.30096pt;width:56.150002px;" version="1.1" viewbox="0 0 56.150002 11.0625" width="56.150002" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,11.0625)"> <g transform="translate(72,-63.15)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代p一个n> <tspan style="font-size: 12.50px; " x="10.890113" y="0"> <</t年代p一个n> <tspan style="font-size: 12.50px; " x="22.930502" y="0"> 0</t年代p一个n> <tspan style="font-size: 12.50px; " x="29.182001" y="0"> 。</t年代p一个n> <tspan style="font-size: 12.50px; " x="32.307751" y="0"> 0</t年代p一个n> <tspan style="font-size: 12.50px; " x="38.559254" y="0"> 1</t年代p一个n> </text> </g> </g> </svg>)。分析响应polyreactivity PfP0显示病人的血清高polyreactive(图<一个href="//www.newsama.com/journals/bmri/2012/695843/fig6/" target="_blank">6 (b)</一个>;中值44.8%)。相比之下,从免疫成年人表现出最小polyreactivity血清蛋白(<年代vg height="10.9125" id="M9" style="vertical-align:-0.17555pt;width:63.962502px;" version="1.1" viewbox="0 0 63.962502 10.9125" width="63.962502" 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p一个n> <tspan style="font-size: 12.50px; " x="10.890113" y="0"> =</t年代p一个n> <tspan style="font-size: 12.50px; " x="22.930502" y="0"> 0</t年代p一个n> <tspan style="font-size: 12.50px; " x="29.182001" y="0"> 。</t年代p一个n> <tspan style="font-size: 12.50px; " x="32.307751" y="0"> 0</t年代p一个n> <tspan style="font-size: 12.50px; " x="38.559254" y="0"> 0</t年代p一个n> <tspan style="font-size: 12.50px; " x="44.810753" y="0"> 1</t年代p一个n> </text> </g> </g> </svg>;中值13.9%)。类似的结果PfP0C0(数据没有显示)。</p> <div class="partial-carousel-wrapper"> <div class="floats-partial-section"> <div class="floats-partial-content"> <div class="partial-carousel--full-image partial-carousel-e370b86159a66e59b54fedbbe945a119"> <div class="partial-carousel--single-image"> <img loading="lazy" alt="" src="https://static.hindawi.com/articles/bmri/volume-2012/695843/figures/695843.fig.005.jpg"> <br> <strong></strong> </div> </div> </div> <div class="floats-partial-middle"> <div class="floats-partial-middle--thumbs"> <div class="partial-carousel-dots-e370b86159a66e59b54fedbbe945a119 partial-carousel-thumbnail"> <button aria-label="Slide to " class="partial-carousel-dot"><img loading="lazy" alt="" src="https://static.hindawi.com/articles/bmri/volume-2012/695843/thumbnails/695843.fig.005_th.jpg"><br><strong></strong></button> </div> </div> <div class="floats-partial-middle--nav"> <div class="partial-carousel-next-prev-e370b86159a66e59b54fedbbe945a119 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p一个n> <a aria-label="View full page" class="caption-partial-url" href="//www.newsama.com/journals/bmri/2012/695843/fig5/" title="" target="_blank"></a> </div> <div class="floats-partial-caption-text"> <table> <tbody> <tr> <td>DNA序列比对的P0<我>恶性疟原虫</我>菌株显示同义突变(黄色标记)在圣卢西亚的压力。其余的序列是相同的菌株。</td> </tr> </tbody> </table> </div> </div> </div> </div> <div class="partial-carousel-wrapper"> <div class="floats-partial-section"> <div class="floats-partial-content"> <div class="partial-carousel--full-image partial-carousel-5045ce3f7e1b5f8c5cb9333c24f25d58"> <div class="partial-carousel--single-image"> <img loading="lazy" alt="(一)" src="https://static.hindawi.com/articles/bmri/volume-2012/695843/figures/695843.fig.006a.jpg"> <br> <strong>(一)</年代trong> </div> <div class="partial-carousel--single-image"> <img loading="lazy" alt="(b)" src="https://static.hindawi.com/articles/bmri/volume-2012/695843/figures/695843.fig.006b.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-5045ce3f7e1b5f8c5cb9333c24f25d58 partial-carousel-thumbnail"> <button aria-label="Slide to (a) " class="partial-carousel-dot"><img loading="lazy" alt="(一)" src="https://static.hindawi.com/articles/bmri/volume-2012/695843/thumbnails/695843.fig.006a_th.jpg"><br><strong>(一)</年代trong></button> <button aria-label="Slide to (b) " class="partial-carousel-dot"><img loading="lazy" alt="(b)" src="https://static.hindawi.com/articles/bmri/volume-2012/695843/thumbnails/695843.fig.006b_th.jpg"><br><strong>(b)</年代trong></button> </div> </div> <div class="floats-partial-middle--nav"> <div class="partial-carousel-next-prev-5045ce3f7e1b5f8c5cb9333c24f25d58 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p一个n> <a aria-label="View full page" class="caption-partial-url" href="//www.newsama.com/journals/bmri/2012/695843/fig6/" title="" target="_blank"></a> </div> <div class="floats-partial-caption-text"> <table> <tbody> <tr> <td>Polyreactive血清anti-PfP0C0响应简单的疟疾患者中观察到,但在免疫成年人生活在高度流行地区。(一)箱形图显示第25和第75百分位数,加上中间,胡须显示最小和最大的区别,圆圈代表的离群值anti-PfP0简单的疟疾病人的血清反应(<年代vg height="11.0375" id="M10" style="vertical-align:-0.27588pt" version="1.1" viewbox="0 0 42.912498 11.0375" width="42.912498" 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,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代p一个n> <tspan style="font-size: 12.50px; " x="9.6773224" y="0"> =</t年代p一个n> <tspan style="font-size: 12.50px; " x="21.71771" y="0"> 4</t年代p一个n> <tspan style="font-size: 12.50px; " x="27.969212" y="0"> 9</t年代p一个n> </text> </g> </g> </svg>)和免疫成人(<年代vg height="10.9125" id="M11" style="vertical-align:-0.17555pt" version="1.1" viewbox="0 0 42.912498 10.9125" width="42.912498" 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p一个n> <tspan style="font-size: 12.50px; " x="9.6773224" y="0"> =</t年代p一个n> <tspan style="font-size: 12.50px; " x="21.71771" y="0"> 3</t年代p一个n> <tspan style="font-size: 12.50px; " x="27.969212" y="0"> 0</t年代p一个n> </text> </g> </g> </svg>在ELISA)决定。(b)箱形图显示第25和第75百分位数,加上中间,胡须显示最小和最大的区别,圆圈代表的离群值% polyreactivity anti-PfP0病人的血清反应和免疫的成年人。DNP-sepharose珠子的血清治疗与否,和anti-PfP0滴定度治疗前后在ELISA测定% polyreactivity决定。</td> </tr> </tbody> </table> </div> </div> </div> </div> <p>Polyreactive自身抗体已报告<我>Plasmodium-chabaudi</我>来华的老鼠(<一个href="#B36">38</一个>]。在临床上发现的自身抗体保护地区的人居住在疟疾省级行政区呈高度流行)类似于那些出现在疾病如系统性红斑狼疮、类风湿关节炎、干燥综合征、多发性肌炎、硬皮病、桥本甲状腺炎。这些可以绑定双和单链DNA,红细胞,免疫球蛋白,核糖核蛋白和烯醇酶。然而,anti-thyroglobulin抗体,autoreactive中B细胞和正常的人,在这样一个人口不增强,这表明这不是一个随机的问题对守恒的抗原非特异性多克隆激活B细胞(<一个href="#B17">18</一个>,<一个href="#B23">25</一个>,<一个href="#B37">39</一个>,<一个href="#B38">40</一个>]。不太可能相同的PfP0宿主蛋白质负责观察polyreactive响应自重复免疫与Pf烯醇酶或牛血清白蛋白耦合PfP0C0 (BSA-PfP0C0)未能诱导polyreactive响应。有趣的是,虽然具体,BSA-PfP0C0政府没有诱导高滴定度anti-PfP0C0响应(滴定度<我>~</我>2<年代vg height="14.375" id="M12" style="vertical-align:-0.3135pt;width:31.85px;" version="1.1" viewbox="0 0 31.85 14.375" width="31.85" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,14.375)"> <g transform="translate(72,-60.5)"> <text transform="matrix(1,0,0,-1,-71.95,60.86)"> <tspan style="font-size: 12.50px; " x="0" y="0"> ×</t年代p一个n> <tspan style="font-size: 12.50px; " x="8.0019197" y="0"> 1</t年代p一个n> <tspan style="font-size: 12.50px; " x="14.25342" y="0"> 0</t年代p一个n> </text> <text transform="matrix(1,0,0,-1,-51.45,66.03)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 4</t年代p一个n> </text> </g> </g> </svg>,图<一个href="//www.newsama.com/journals/bmri/2012/695843/fig4/" target="_blank">4 (e)</一个>)。然而,这种反应是autoreactive,因为血清反应鼠标P0C0,尽管十倍低浓度(滴定度~ 2<年代vg height="14.375" id="M13" style="vertical-align:-0.3135pt;width:31.85px;" version="1.1" viewbox="0 0 31.85 14.375" width="31.85" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,14.375)"> <g transform="translate(72,-60.5)"> <text transform="matrix(1,0,0,-1,-71.95,60.86)"> <tspan style="font-size: 12.50px; " x="0" y="0"> ×</t年代p一个n> <tspan style="font-size: 12.50px; " x="8.0019197" y="0"> 1</t年代p一个n> <tspan style="font-size: 12.50px; " x="14.25342" y="0"> 0</t年代p一个n> </text> <text transform="matrix(1,0,0,-1,-51.45,66.03)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 3</t年代p一个n> </text> </g> </g> </svg>数据未显示)。因此,潜在autoreactive抗原决定基耦合到载体蛋白未能产生polyreactive应答,但包含61 - 316年的重组蛋白氨基酸诱导low-titre, polyreactive响应。这表明能力诱导polyreactivity可能在于61−300地区的蛋白质。也有可能蛋白质的构象是polyreactivity感应的一个重要因素,或者rPfP0就像一个B细胞分裂素。还需要进一步的调查来确定一个特定的区域和/或蛋白质的构象结构负责诱导polyreactive响应。</p> <p>正常的人类血清含天然自身抗体可以识别自体抗原(<一个href="#B39">41</一个>]。分析人类单克隆抗体来源于正常外周血B细胞表明天然自身抗体polyreactive和表达生殖系免疫球蛋白可变区基因很少或根本没有体细胞突变(<一个href="#B40">42</一个>,<一个href="#B41">43</一个>),虽然在affinity-matured polyreactivity也被观察到抗体(<一个href="#B42">44</一个>]。平衡能力采用多种构象状态允许polyreactive抗体绑定多个结构无关抗原(<一个href="#B43">45</一个>]。Polyreactive抗体诱导的小鼠模型已报告疟疾(<一个href="#B36">38</一个>]。我们表明,免疫parasite-derived蛋白质也能导致polyreactive响应。有趣的是,我们发现人们患有疟疾也表现出PfP0 polyreactive反应。这polyreactive反应是局限于病人,因为成人免疫血清显示一个相对nonpolyreactive反应的蛋白质。之前我们已经表明,PfP0表达表面裂殖子(<一个href="#B17">18</一个>]。因此,它可能是暴露在低水平的蛋白质(如免疫的情况下会发生的地方性成年人)结果在特定反应的蛋白质,和这个特定的反应疾病预防疟疾。暴露于高剂量的蛋白质(例如,在活动期间疟疾疾病或免疫协议),另一方面,可能导致polyreactive响应。还需要进一步的调查来看看低剂量的PfP0有或没有一个强有力的辅助导致特定anti-PfP0反应。</p> <p>抗体有关键作用的控制疟疾感染。调理素作用的寄生虫抗体蛋白质表达裂殖子或感染的红细胞表面有助于它们被巨噬细胞清除和最终的破坏(<一个href="#B44">46</一个>]。疟疾寄生虫已经证明可以破坏宿主的免疫系统以多种方式包括抗原变异和抗原的多态性,干扰树突状细胞成熟,诱导细胞凋亡在内存中B和T细胞(<一个href="#B45">47</一个>- - - - - -<一个href="#B48">50</一个>]。在这里,我们表明,守恒,parasite-derived宿主蛋白诱导的体液反应。表达倾向或分泌的抗原诱导弱polyreactive体液反应可能是一个加强寄生虫生存机制。</p> <h4 id="abbreviations">缩写</h4> <table class="gloss-abbr" style="font-size:12px"> <tbody> <tr> <td align="left">PfP0:</td> <td align="left"><i>恶性疟原虫</我>P0</td> </tr> <tr> <td align="left">rPfP0:</td> <td align="left">重组PfP0</td> </tr> <tr> <td align="left">PfP0C0:</td> <td align="left">PfP0 Carboxy-terminal 16个氨基酸</td> </tr> <tr> <td align="left">系统性红斑狼疮:</td> <td align="left">系统性红斑狼疮</td> </tr> <tr> <td align="left">马伯:</td> <td align="left">单克隆抗体</td> </tr> <tr> <td align="left">DNP:</td> <td align="left">Dinitrophenyl</td> </tr> <tr> <td align="left">TgP0:</td> <td align="left"><i>刚地弓形虫</我>P0</td> </tr> <tr> <td align="left">BSA-PfP0C0:</td> <td align="left">牛血清白蛋白PfP0C0耦合。</td> </tr> </tbody> </table> <h4 id="acknowledgments">确认</h4> <p>作者欣然承认博士Pierre-Andre Cazenave的批判阅读手稿。他们也感谢Das和n金达尔博士的输入。本研究使用资金的原子能,印度政府。美国帕沙克和k . 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14"> <defs> <clippath id="a"> <path d="M10.293,13.707a1,1,0,0,1,0-1.414L14.586,8H1A1,1,0,0,1,1,6H14.586L10.293,1.707A1,1,0,0,1,11.707.293l6,6a1,1,0,0,1,.172.231h0l.01.019,0,.005.007.014.006.012,0,.008.008.018v0a1,1,0,0,1-.009.817l0,0L17.9,7.44l0,.009-.005.011-.007.013,0,.008-.008.015,0,.005-.01.016,0,0-.011.017,0,0-.012.018,0,0-.012.017,0,0L17.8,7.6l0,0-.011.014,0,.006-.01.012-.009.011-.006.007-.015.017h0l-.04.042-6,6a1,1,0,0,1-1.414,0Z" transform="translate(3 5)"></path> </clippath> </defs> <g transform="translate(-3 -5)"> <path d="M10.293,13.707a1,1,0,0,1,0-1.414L14.586,8H1A1,1,0,0,1,1,6H14.586L10.293,1.707A1,1,0,0,1,11.707.293l6,6a1,1,0,0,1,.172.231h0l.01.019,0,.005.007.014.006.012,0,.008.008.018v0a1,1,0,0,1-.009.817l0,0L17.9,7.44l0,.009-.005.011-.007.013,0,.008-.008.015,0,.005-.01.016,0,0-.011.017,0,0-.012.018,0,0-.012.017,0,0L17.8,7.6l0,0-.011.014,0,.006-.01.012-.009.011-.006.007-.015.017h0l-.04.042-6,6a1,1,0,0,1-1.414,0Z" transform="translate(3 5)" fill="currentColor"></path> </g> </svg></span></a> <div class="articleToolbarStatistics_articleToolbarStatistics__8_woN"> <div class="articleToolbarStatistics_column__R2GqD"> <div> <div> <span>的观点</年代p一个n> <div class="articleToolbarStatistics_amount__vJIDp"> 1323年</d我v> </div> <div> <span>下载</年代p一个n> <div class="articleToolbarStatistics_amount__vJIDp"> 1137年</d我v> </div> </div> </div> <div class="articleToolbarStatistics_column__R2GqD articleToolbarStatistics_dimensions__pe7pO"> <div> 引用</d我v> <span class="__dimensions_badge_embed__ articleToolbarStatistics_circle__p2dSc" data-doi="10.1155/2012/695843" data-style="small_circle"></span> </div> </div> <ul class="articleToolbarSocials_articleToolbarSocials__g02HH"> <li><a href="https://twitter.com/share?url=https://doi.org/10.1155/2012/695843&via=Hindawi" unselectable="on" title="" rel="noopener noreferrer" target="_blank"><span role="img" class="anticon"> <svg xmlns="http://www.w3.org/2000/svg" width="1em" height="1em" viewbox="126.444 2.281 589 589"> <circle 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5.1±1.3×104). Pathological changes were observed in the mice after seven boosts. Adsorption with dinitrophenyl hapten revealed that the anti-PfP0C0 response was largely polyreactive. This polyreactivity was distributed across all isotypes. Similar polyreactive responses to PfP0 and PfP0C0 were observed in sera from malaria patients. Our data suggests that PfP0 induces a deviant humoral response, and this may contribute to immune evasion mechanisms of the parasite. "> 疟原虫Riboprotein PfP0引发一个异常Balb / c小鼠的体液免疫反应</t我tle> <link rel="preload stylesheet" as="style" type="text/css" href="https://cdn.bibblio.org/rcm/4.28.0/bib-related-content.min.css"> <link rel="preload" href="https://static.hindawi.com/new/next_assets/2023-08-03-0017a694320dbe69a559e8120be98c/_next/static/css/b2661f2cd4bd618b.css" as="style"> <link rel="stylesheet" href="https://static.hindawi.com/new/next_assets/2023-08-03-0017a694320dbe69a559e8120be98c/_next/static/css/b2661f2cd4bd618b.css" data-n-g=""> <style id="__jsx-903e4b2e5d3241e4">div#__next{display:-webkit-box;display:-webkit-flex;display:-moz-box;display:-ms-flexbox;display:flex;min-height:100vh;-webkit-box-orient:vertical;-webkit-box-direction:normal;-webkit-flex-direction:column;-moz-box-orient:vertical;-moz-box-direction:normal;-ms-flex-direction:column;flex-direction:column}</style> </head> <body> <div id="__next"> <section class="ant-layout"> <div> <header class="ant-layout-header"> <div class="header__width-wrapper"> 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<div> <div> <div id="article-table-of-contents" data-ismobile="false"> <div class="TableOfContents_tableOfContents__0jAuv"> <div class="TableOfContents_tableOfContents__title__CH9Lz"> 在这一页上</d我v> <a class="TableOfContents_tableOfContents__item__JJil1" href="#abstract">文摘</一个> <a class="TableOfContents_tableOfContents__item__JJil1" href="#introduction">介绍</一个> <a class="TableOfContents_tableOfContents__item__JJil1" href="#materials-and-methods">材料和方法</一个> <a class="TableOfContents_tableOfContents__item__JJil1" href="#results-and-discussion">结果与讨论</一个> <a class="TableOfContents_tableOfContents__item__JJil1" href="#abbreviations">缩写</一个> <a class="TableOfContents_tableOfContents__item__JJil1" href="#acknowledgments">确认</一个> <a class="TableOfContents_tableOfContents__item__JJil1" href="#references">引用</一个> <a class="TableOfContents_tableOfContents__item__JJil1" href="#copyright">版权</一个> <a class="TableOfContents_tableOfContents__item__JJil1" 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p一个n> <h2 class="articleHeader__specialIssue_title">2011年寄生虫病免疫学和细胞生物学</h2> <a href="//www.newsama.com/journals/bmri/si/824978/" class="articleHeader__specialIssue_url" target="_blank" rel="noreferrer">把这个特殊的问题</一个> </div> <strong>研究文章|开放获取</年代trong> <div class="articleHeader__meta"> <span>体积2012年|</年代p一个n> <span>文章的ID695843年|</年代p一个n> <span class="articleHeader__meta_doiLink"><a href="https://doi.org/10.1155/2012/695843" aria-label="Doi-link" target="_blank" rel="noreferrer">https://doi.org/10.1155/2012/695843</一个></span> </div> <div class="simpleShowMore"> <button class="simpleShowMore__button">显示引用</button> </div> <h1 class="articleHeader__title"><i>疟原虫</我>Riboprotein PfP0诱发Balb /异常体液免疫反应<我>c</我>老鼠</h1> <div class="articleHeader__authors"> <span class="articleHeader__authors_author"><strong>Sulabha帕沙克</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">k . Rajeshwari,<年代up>1、2</年代up></span> <span class="articleHeader__authors_author">斯瓦特Garg,<年代up>1</年代up></span> <span class="articleHeader__authors_author">Sudarsan Rajagopal,<年代up>1</年代up></span> <span class="articleHeader__authors_author">Kalpesh帕特尔,<年代up>1、3</年代up></span> <span class="articleHeader__authors_author">Bidyut Das,<年代up>4</年代up></span> <span class="articleHeader__authors_author">方法斑驳的,<年代up>5</年代up></span> <span class="articleHeader__authors_author">Balachandran文德兰花,<年代up>6</年代up></span> <span class="articleHeader__authors_author">和Shobhona沙玛<年代up>1</年代up></span> </div> <div class="simpleShowMore"> <button class="simpleShowMore__button">显示更多</button> </div> <div class="articleHeader__academicEditor"> <strong>学术编辑器:</年代trong> <span>Jorge Morales-Montor</年代p一个n> </div> <div class="articleHeader__timeline"> <div class="articleHeader__timeline_item "> <strong>收到了</年代trong> <span>05年7月2011年</年代p一个n> </div> <div class="articleHeader__timeline_item "> <strong>修改后的</年代trong> <span>2011年9月30日</年代p一个n> </div> <div class="articleHeader__timeline_item "> <strong>接受</年代trong> <span>2011年10月02</年代p一个n> </div> <div class="articleHeader__timeline_item articleHeader__timeline_item_sticky"> <strong>发表</年代trong> <span>2012年1月17日</年代p一个n> </div> </div> </div> <div class="articleBody"> <div class="xml-content"> <h4 class="header" id="abstract">文摘</h4> <p>被动免疫抗体的重组<我>恶性疟原虫</我>P0 riboprotein (rPfP0, 61 - 316个氨基酸)提供了防止疟疾。Carboxy-terminal 16个氨基酸的蛋白质(PfP0C0)是守恒的,显示69%的人类和小鼠P0身份。抗体这一领域中发现10 - 15%的系统性红斑狼疮患者。我们对体液反应的本质与rPfP0 PfP0C0通过多次免疫小鼠。我们未能提高稳定anti-PfP0C0杂种细胞从任何的21个老鼠。平均血清anti-PfP0C0效价仍低(<年代vg height="15.3375" id="M1" style="vertical-align:-1.09097pt;width:95.525002px;" version="1.1" viewbox="0 0 95.525002 15.3375" width="95.525002" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,15.3375)"> <g transform="translate(72,-59.73)"> <text transform="matrix(1,0,0,-1,-71.95,60.86)"> <tspan style="font-size: 12.50px; " x="0" y="0"> 5</t年代p一个n> <tspan style="font-size: 12.50px; " x="6.2515001" y="0"> 。</t年代p一个n> <tspan style="font-size: 12.50px; " x="9.3772497" y="0"> 1</t年代p一个n> <tspan style="font-size: 12.50px; " x="18.404415" y="0"> ±</t年代p一个n> <tspan style="font-size: 12.50px; " x="29.744637" y="0"> 1</t年代p一个n> <tspan style="font-size: 12.50px; " x="35.996136" y="0"> 。</t年代p一个n> <tspan style="font-size: 12.50px; " x="39.121887" y="0"> 3</t年代p一个n> <tspan style="font-size: 12.50px; " x="48.149052" y="0"> ×</t年代p一个n> <tspan style="font-size: 12.50px; " x="58.92664" y="0"> 1</t年代p一个n> <tspan style="font-size: 12.50px; " x="65.178139" y="0"> 0</t年代p一个n> </text> <text transform="matrix(1,0,0,-1,-0.51,66.03)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 4</t年代p一个n> </text> </g> </g> </svg>)。病理变化观察七增强后的老鼠。吸附与dinitrophenyl半抗原显示主要polyreactive anti-PfP0C0反应。这个polyreactivity分布在所有的同形像。类似polyreactive应对PfP0和PfP0C0观察疟疾患者的血清。我们的数据表明,PfP0诱发异常体液反应,这可能导致寄生虫的免疫逃避机制。</p> <span class="end-abs"></span> <h4 id="introduction">1。介绍</h4> <p>核糖体磷蛋白质P0中性是一个高度保守的蛋白质在60年代的真核生物核糖体亚基(<一个href="#B1">1</一个>]。P0,连同相关的酸性核糖体磷蛋白质P1和P2,形成pentameric蛋白质复合体(P1)<年代ub>2</年代ub>p0 - (P2)<年代ub>2</年代ub>有一个角色在组装GTPase-binding网站的大亚基的核糖体(<一个href="#B2">2</一个>- - - - - -<一个href="#B4">4</一个>]。P0是至关重要的细胞生存敲出来是致命的<我>酿酒酵母</我>和<我>鼠体内</我>(<一个href="#B5">5</一个>,<一个href="#B100">6</一个>]。它被假定有多个其他功能包括apurinic-apyrimidinic酶活动<我>黑腹果蝇</我>(<一个href="#B6">7</一个>),调节基因表达<我>果蝇</我>在人类中,细胞凋亡和致癌作用[<一个href="#B6">7</一个>- - - - - -<一个href="#B9">10</一个>]。P0已被证明是表面上的<我>疟原虫spp,刚地弓形虫</我>,<我>酿酒酵母</我>(<一个href="#B10">11</一个>)以及表面上的神经,肝和其他细胞系(<一个href="#B11">12</一个>,<一个href="#B12">13</一个>]。人类P蛋白已经被广泛的研究,因为它们与系统性红斑狼疮(SLE),一种自身免疫性疾病。大约10 - 15%的病人患有系统性红斑狼疮拥有自身抗体对守恒16 carboxy-terminal氨基酸(<一个href="#B13">14</一个>]。Clustal分析表明,这一地区的蛋白在不同物种高度保守的<一个href="#B14">15</一个>]。人类和小鼠P0,例如,仅在六个不同氨基酸和狼疮域(图是相同的<一个href="//www.newsama.com/journals/bmri/2012/695843/fig1/" target="_blank">1</一个>)。我们曾表明,87%的成年居民高传播疟疾地区的印度东部拥有抗体<我>恶性疟原虫</我>P0 (PfP0) [<一个href="#B15">16</一个>]。同样,60%的成年人居住在肯尼亚显示大量的t细胞反应PfP0蛋白(<一个href="#B16">17</一个>]。多克隆和单克隆抗体PfP0已被证明阻止疟原虫入侵红细胞<我>在体外</我>和<我>在活的有机体内</我>(<一个href="#B14">15</一个>,<一个href="#B17">18</一个>,<一个href="#B18">19</一个>]。当我们试图提高单克隆抗体(mab)对主要的PfP0片段,重组PfP0 (rPfP0 61−316个氨基酸),我们发现第一个鼠标,收到7注射(4周,3月),导致了不稳定的杂种细胞对氨基酸的蛋白质。第二只老鼠收到9注射蛋白质(4周,5月),引发了几个独立的马伯克隆,其中大部分是专门应对极端carboxy-terminal PfP0C0(300−316氨基酸,图<一个href="//www.newsama.com/journals/bmri/2012/695843/fig1/" target="_blank">1</一个>)[<一个href="#B18">19</一个>]。这个鼠标的血清反应只与rPfP0 PfP0C0,但不承认其他重叠肽来源于蛋白质(<一个href="#B200">20.</一个>]。向人类P0 carboxy-terminal PfP0C0显示,69%身份。这种优势的抗体对红斑狼疮域可能是由于老鼠的年龄(8个月),因为故障重复免疫接种后免疫耐受,或两者兼而有之。或者,它可能是一个特殊的老鼠的反应。</p> <div class="partial-carousel-wrapper"> <div class="floats-partial-section"> <div class="floats-partial-content"> <div class="partial-carousel--full-image partial-carousel-59f726cbd1f28af5905a12c8c7051bb7"> <div class="partial-carousel--single-image"> <img loading="lazy" alt="" src="https://static.hindawi.com/articles/bmri/volume-2012/695843/figures/695843.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-59f726cbd1f28af5905a12c8c7051bb7 partial-carousel-thumbnail"> <button aria-label="Slide to " class="partial-carousel-dot"><img loading="lazy" alt="" src="https://static.hindawi.com/articles/bmri/volume-2012/695843/thumbnails/695843.fig.001_th.jpg"><br><strong></strong></button> </div> </div> <div class="floats-partial-middle--nav"> <div class="partial-carousel-next-prev-59f726cbd1f28af5905a12c8c7051bb7 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p一个n> <a aria-label="View full page" class="caption-partial-url" href="//www.newsama.com/journals/bmri/2012/695843/fig1/" title="" target="_blank"></a> </div> <div class="floats-partial-caption-text"> <table> <tbody> <tr> <td>PfP0示意图表示,重组PfP0, PfP0C0 P0多重序列比对。</td> </tr> </tbody> </table> </div> </div> </div> </div> <p>PfP0自anti-PfP0抗体是一个潜在的候选疫苗被证明防止疟疾感染小鼠模型(<一个href="#B17">18</一个>,<一个href="#B18">19</一个>]。因为它的守恒性质和carboxy-terminal域对人类的同源蛋白质,它也可能表现得像一个自身抗原。确定很重要的质量和数量引起的体液反应重复免疫接种后的蛋白质。因此,我们进行了这个系统的研究中,我们试图提高对PfP0C0马伯rPfP0多次免疫接种。中央和周边水平选择流程管理B细胞的生存能力对一个特定的免疫原,而外围抗原驱动选择流程确定体液反应的类型和程度。我们推断,如果脾B细胞的反映整个B细胞反应和B细胞特异性不偏见混合形成,然后形成杂种细胞的频率应该反映PfP0不同抗原表位的免疫原性。我们还研究了血清anti-PfP0C0反应的本质。</p> <p>我们未能提高单个anti-PfP0C0杂种细胞从任何的21个老鼠用于这些后续的实验,表明第一次成功地提高杂种细胞对PfP0C0域可能是由于一个不寻常的反应中观察到,一个鼠标(结合23两项研究中使用的老鼠)。我们观察到结缔组织纤维化脾脏的免疫接种程序的第四个月,逐渐的增加与进一步的免疫接种。尸检显示病变的肝脏、心脏、肾脏和肺的老鼠。平均血清anti-PfP0C0滴定度保持低(<年代vg height="15.3375" id="M2" style="vertical-align:-1.09097pt;width:95.525002px;" version="1.1" viewbox="0 0 95.525002 15.3375" width="95.525002" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,15.3375)"> <g transform="translate(72,-59.73)"> <text transform="matrix(1,0,0,-1,-71.95,60.86)"> <tspan style="font-size: 12.50px; " x="0" y="0"> 5</t年代p一个n> <tspan style="font-size: 12.50px; " x="6.2515001" y="0"> 。</t年代p一个n> <tspan style="font-size: 12.50px; " x="9.3772497" y="0"> 1</t年代p一个n> <tspan style="font-size: 12.50px; " x="18.404415" y="0"> ±</t年代p一个n> <tspan style="font-size: 12.50px; " x="29.744637" y="0"> 1</t年代p一个n> <tspan style="font-size: 12.50px; " x="35.996136" y="0"> 。</t年代p一个n> <tspan style="font-size: 12.50px; " x="39.121887" y="0"> 3</t年代p一个n> <tspan style="font-size: 12.50px; " x="48.149052" y="0"> ×</t年代p一个n> <tspan style="font-size: 12.50px; " x="58.92664" y="0"> 1</t年代p一个n> <tspan style="font-size: 12.50px; " x="65.178139" y="0"> 0</t年代p一个n> </text> <text transform="matrix(1,0,0,-1,-0.51,66.03)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 4</t年代p一个n> </text> </g> </g> </svg>)即使10助推器。Dinitrophenyl (DNP)吸附研究表明,很大程度上是polyreactive体液反应。这polyreactivity并不局限于任何特定的免疫球蛋白同形像,而是分布在所有同形像。序列分析的七个杂种细胞获得最初的研究显示,他们来自一个克隆。我们从简单的疟疾病人血清分析确定蛋白质polyreactivity的程度。我们分析发现一个类似polyreactive应对PfP0和PfP0C0在这些血清抗原决定基。我们的数据表明,PfP0诱发小鼠的体液反应。感应的越轨,low-titre polyreactive反应可能逃避宿主的免疫系统的一种方法。</p> <h4 id="materials-and-methods">2。材料和方法</h4> <h5 id="sec2.1">2.1。老鼠</h5> <p>六个雌性Balb /<我>c</我>老鼠从当地的动物育种获得设备的塔塔理工学院基础研究,孟买,印度。老鼠在特定的无菌条件下培育和维护。所有的实验研究是根据建议进行CPCSEA(委员会控制和监督的目的动物实验)。</p> <h5 id="sec2.2">2.2。免疫接种和建立杂种细胞</h5> <p>免疫原和肽:表达和纯化的重组PfP0(氨基酸61−316)作为GST融合蛋白做了如前所述[<一个href="#B19">21</一个>]。的重组<我>大肠杆菌</我>细胞包含<我>PfP0</我>出了基因片段2 h在37°C,用IPTG诱导,收割,细胞溶解。细胞溶解产物离心机,包含融合蛋白和不溶性微粒分数是决定SDS-polyacrylamide制备凝胶。一条重组蛋白的凝胶对应MW切除,electroeluted,对PBS分离,集中。的身份证实了蛋白质免疫印迹分析描述(<一个href="#B20">22</一个>]。蚁脑匀浆,<我>恶性疟原虫</我>磷酸果糖激酶,<我>恶性疟原虫</我>烯醇酶准备描述(<一个href="#B21">23</一个>- - - - - -<一个href="#B23">25</一个>]。P0蛋白质<我>刚地弓形虫</我>(TgP0)在pGEX4T1克隆和表达GST融合蛋白。重组,全身的销售税−TgP0提取使用sarkosyl[从诱导细胞颗粒<一个href="#B24">26</一个>),纯化使用谷胱甘肽琼脂糖珠从溶解产物(通用电气医疗集团),与PBS包含150毫米生理盐水冲洗三次,并使用100毫米谷胱甘肽筛选了。蛋白质的身份被确认使用sds - page和免疫印迹(数据未显示)牛血清白蛋白耦合PfP0C0 (BSA-PfP0C0)准备如前所述<一个href="#B18">19</一个>]。</p> <p>合成肽MoP0C0 (EESEESDEDMGFGLFD) PfP0C0 (EEEEEEDGFMGFGMFD)获得Mimotopes,堪培拉,澳大利亚。牛胰岛素,ssDNA, dsDNA从σ(圣路易斯,密苏里州,美国)。</p> <p>免疫和杂种细胞建立是描述Rajeshwari et al ., 2004<一个href="#B18">19</一个>]。简单地说,50<我>μ</我>gs的蛋白质在弗氏佐剂乳化在小鼠腹腔接种。动物收到四个每周注射之后,每月注射。除了第一个用弗氏完全佐剂免疫,免疫接种工作的其他弗氏不完全佐剂。4天在融合之前,250年的老鼠了<我>μ</我>克盐水的免疫原。老鼠牺牲每个每月注射后,血清收集,脾脏被收获,脾细胞与小鼠骨髓瘤Sp2/0细胞融合。Antibody-secreting克隆选择通过ELISA (<一个href="#B25">27</一个>]。Immunogen-recognizing杂种细胞被subcloned monoclonality通过限制稀释。rPfP0免疫,老鼠放弃7月免疫接种;三个老鼠牺牲后每个月免疫。</p> <h5 id="sec2.3">2.3。人类血清样本</h5> <p>血清样本收集从简单的疟疾病人以及免疫成年人生活在高度流行区在奥里萨邦,印度。存在与否<我>恶性疟原虫</我>感染是由显微镜检查确认Giemsa-stained厚薄血液涂片或通过使用商业套装。知情同意后收集到的样本,从道德委员会获得必要的许可后,渣打银行医学院和医院,Cuttack、印度。</p> <h5 id="sec2.4">2.4。ELISA</h5> <p>抗体反应是由ELISA (<一个href="#B18">19</一个>]。短暂,Maxisorp板块(Nunc、鲁开德、丹麦)涂在一夜之间在4°C全抗原(5<我>μ</我>g / mL)或合成肽(200 ng / mL)在PBS, pH值7.2。盘子被封锁的1% BSA之前添加杂种细胞上清液或适当的稀释血清,用兔子anti-mouse Ig共轭开发辣根过氧化物酶(勃林格曼海姆,曼海姆,德国)和abt(勃林格曼海姆),和吸光度(光密度;OD)为405 nm EL808超微型板块读者(美国Biotek仪器公司、Winooski VT)。</p> <p>探测polyreactivity DNP是共轭CNBr-activated琼脂糖珠(通用电气医疗集团,小都,白金汉郡,英国)按照制造商的指示。简而言之,2,4-DNP -<我>ε</我>赖氨酸(σ)溶解在0.1 M NaHCO3 pH值8.3包含0.5 M氯化钠,加入琼脂糖珠在1毫米HCl肿胀,和孵化立式圆筒形混合器在室温下1 h。洗掉多余的配体后,活跃的网站被封锁使用0.1米Tris-HCl缓冲区,pH值8.0。的珠子用三周期0.1乙酸/醋酸钠,pH值4.0包含0.5 M氯化钠,后跟一个用0.1 Tris-HCl, pH值8包含0.5 M氯化钠。整除的血清稀释与否与孵化DNP-sepharose珠子章动器和离心机为1.5小时。上层清液稀释进一步用于ELISA。polyreactivity百分比计算下:<年代p一个ncl一个年代年代="equation" id="eq1"> <svg height="57.950001" id="M3" preserveaspectratio="xMaxYMin" style="vertical-align:-0pt;width:700.9375px;" version="1.1" viewbox="0 0 700.9375 57.950001" width="700.9375" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,57.95)"> <g transform="translate(72,-25.64)"> <text transform="matrix(1,0,0,-1,51.43,63.12)"> <tspan style="font-size: 12.50px; " x="3.47" y="28.51"> =</t年代p一个n> <tspan style="font-size: 12.50px; " x="0" y="0"> %</t年代p一个n> <tspan style="font-size: 12.50px; " x="13.50324" y="0"> p</t年代p一个n> <tspan style="font-size: 12.50px; " x="19.75474" y="0"> o</t年代p一个n> <tspan style="font-size: 12.50px; " x="26.006241" y="0"> l</t年代p一个n> <tspan style="font-size: 12.50px; " x="29.232014" y="0"> y</t年代p一个n> <tspan style="font-size: 12.50px; " x="35.483513" y="0"> r</t年代p一个n> <tspan style="font-size: 12.50px; " x="39.622005" y="0"> e</t年代p一个n> <tspan style="font-size: 12.50px; " x="45.17334" y="0"> 一个</t年代p一个n> <tspan style="font-size: 12.50px; " x="50.72467" y="0"> c</t年代p一个n> <tspan style="font-size: 12.50px; " x="56.276005" y="0"> t</t年代p一个n> <tspan style="font-size: 12.50px; " x="59.751839" y="0"> 我</t年代p一个n> <tspan style="font-size: 12.50px; " x="63.227673" y="0"> v</t年代p一个n> <tspan style="font-size: 12.50px; " x="69.479172" y="0"> 我</t年代p一个n> <tspan style="font-size: 12.50px; " x="72.955002" y="0"> t</t年代p一个n> <tspan style="font-size: 12.50px; " x="76.43084" y="0"> y</t年代p一个n> <tspan style="font-size: 12.50px; " x="16.700001" y="21.25"> O</t年代p一个n> <tspan style="font-size: 12.50px; " x="25.727165" y="21.25"> D</t年代p一个n> <tspan style="font-size: 12.50px; " x="38.917831" y="21.25"> o</t年代p一个n> <tspan style="font-size: 12.50px; " x="45.169331" y="21.25"> f</t年代p一个n> <tspan style="font-size: 12.50px; " x="53.49633" y="21.25"> u</t年代p一个n> <tspan style="font-size: 12.50px; " x="59.747829" y="21.25"> n</t年代p一个n> <tspan style="font-size: 12.50px; " x="65.999329" y="21.25"> 一个</t年代p一个n> <tspan style="font-size: 12.50px; " x="71.550659" y="21.25"> d</t年代p一个n> <tspan style="font-size: 12.50px; " x="77.802162" y="21.25"> 年代</t年代p一个n> <tspan style="font-size: 12.50px; " x="82.665825" y="21.25"> o</t年代p一个n> <tspan style="font-size: 12.50px; " x="88.917328" y="21.25"> r</t年代p一个n> <tspan style="font-size: 12.50px; " x="93.080826" 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x="344.60349" y="-19.83"> 1</t年代p一个n> <tspan style="font-size: 12.50px; " x="350.85501" y="-19.83"> )</t年代p一个n> </text> </g> </g> </svg></span></p> <h5 id="sec2.5">2.5。测定RNA序列Anti-PfP0C0马伯克隆</h5> <p>Anti-PfP0C0抗体生产杂种细胞克隆(1 a4, b3、2 c11、1 e5f4 1 f6, 2 g1和2 h1)细胞溶解在试剂盒(美国表达载体,卡尔斯巴德,CA)和RNA制备根据制造商的协议。RNA的互补脱氧核糖核酸制备使用3′底漆(重或轻链恒定底漆)和MMLV逆转录酶(内)。PCR扩增的轻、重链进行使用引物中描述表<一个href="//www.newsama.com/journals/bmri/2012/695843/tab1/" target="_blank">1</一个>。用来放大PCR片段如下条件:DNA融化在91°C 1分钟,2分钟引物退火52°C,聚合酶扩展在72°C 1.5分钟30周期进行。PCR克隆产品TA pGEM-T向量系统(WI Promega,麦迪逊,美国),和结扎混合变换XL-1蓝色<我>大肠杆菌</我>细菌。阳性克隆测序使用M13F (5′d [GTAAAACGACGGCCAG] 3′)和M13R (5′d [CAGGAAACAGCTATGAC] 3′)引物。</p> <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p一个n> <a aria-label="View full page" class="caption-partial-url" href="//www.newsama.com/journals/bmri/2012/695843/tab1/" title="" target="_blank"></a> </div> <div class="floats-partial-caption-text"> 引物用于增强抗体可变区。</d我v> <a class="table-thumb-overlay" href="//www.newsama.com/journals/bmri/2012/695843/tab1" target="_blank" aria-label="View full page"></a> </div> </div> <h5 id="sec2.6">2.6。统计分析</h5> <p>成对Wilcoxan符号秩检验是用来比较和评价的统计意义unadsorbed和小鼠血清吸附OD。非参数Mann-Whitney测试是用来评估人类血清数据的统计学意义。GraphPad Instat软件被用于分析。</p> <h4 id="results-and-discussion">3所示。结果与讨论</h4> <h5 id="sec3.1">3.1。重组PfP0免疫接种失败的产量稳定Anti-PfP0C0马伯生产杂种细胞</h5> <p>我们有兴趣提高马伯重组<我>恶性疟原虫</我>核糖体蛋白P0 (PfP0)多克隆抗体这种蛋白质有抑制疟原虫入侵红细胞(<一个href="#B14">15</一个>,<一个href="#B18">19</一个>]。在先前的研究中,我们成功地提高稳定马伯反对PfP0经过多次免疫只在一个鼠标,和大多数的人反对PfP0C0 [<一个href="#B18">19</一个>]。极端的c端域以来人类P0蛋白质同源PfP0羧基端(PfP0C0;300−316个氨基酸),是主要的p蛋白质自身抗原参与红斑狼疮(<一个href="#B13">14</一个>),我们有兴趣探索的性质PfP0C0体液反应,想要确定我们会获得马伯的频率对这个领域PfP0蛋白质。全长蛋白显示了极其可怜的表达式,因此我们使用了大片段的蛋白质(rPfP0 61−316个氨基酸)免疫接种。</p> <p>我们6免疫Balb /<我>c</我>小鼠4周注射rPfP0弗氏完全佐剂,紧随其后的是每月的助推器。小鼠脾脏从3每个月注射后收获杂种细胞的准备(5日到11日免疫)的。表<一个href="//www.newsama.com/journals/bmri/2012/695843/tab2/" target="_blank">2</一个>,显示结果为5日,7日,9日和11日免疫。类似的结果剩下的时间点。从表<一个href="//www.newsama.com/journals/bmri/2012/695843/tab2/" target="_blank">2</一个>,我们未能获得任何稳定的克隆对PfP0C0,尽管一再免疫接种或老鼠的年龄。克隆筛选约1800只取得了22个稳定的克隆。大多数克隆polyreactive或停止抗体生产几天之内,未能认识到carboxy-terminal抗原决定基。因此,无论是动物的年龄还是重复与潜在的自身抗原免疫接种可以成功的原因提高杂种细胞的初步研究。</p> <div class="floats-partial-section partial-other-wrapper" data-section="tab2"> <div class="floats-partial-footer"> <div class="floats-partial-caption"> <span class="caption-text">表2</年代p一个n> <a aria-label="View full page" class="caption-partial-url" href="//www.newsama.com/journals/bmri/2012/695843/tab2/" title="" target="_blank"></a> </div> <div class="floats-partial-caption-text"> 后血清滴定度和杂种细胞获得重复免疫与各种蛋白质。</d我v> <a class="table-thumb-overlay" href="//www.newsama.com/journals/bmri/2012/695843/tab2" target="_blank" aria-label="View full page"></a> </div> </div> <p>我们无法提高稳定的杂种细胞对PfP0C0不能归咎于错误的技术,因为我们成功获得多个稳定的克隆对多种蛋白质(表<一个href="//www.newsama.com/journals/bmri/2012/695843/tab2/" target="_blank">2</一个>)。这些包括蚁脑匀浆,<我>果蝇</我>用鼠标translin熊52%同源性蛋白(<一个href="#B26">28</一个>),寄生虫蛋白质等<我>恶性疟原虫</我>果糖激酶,<我>β</我>和潜在autoantigenic蛋白质等<我>恶性疟原虫</我>烯醇酶(<一个href="#B27">29日</一个>,<一个href="#B28">30.</一个>)和TgP0。PfP0的身份和鼠标P0糖基在极端的16个氨基酸是69%(图<一个href="//www.newsama.com/journals/bmri/2012/695843/fig1/" target="_blank">1</一个>)。这同源PfP0鼠标P0独自不能缺乏杂种细胞的唯一原因,因为<我>恶性疟原虫</我>烯醇酶和TgP0显示相当大的同源性与鼠标烯醇酶和鼠标P0(75%和62.5%,分别地。),而这些都服从一代杂种细胞大量的稳定。二次抗原挑战导致代长寿的浆细胞能够分泌高亲和性抗体免疫抗原(<一个href="#B29">31日</一个>]。人们很容易推测PfP0是一个不寻常的抗原,它未能引起一个健壮的B细胞反应,因为重复免疫产生稳定的杂种细胞很少,而且都不是针对抗原的免疫原性羧基端。</p> <h5 id="sec3.2">3.2。马伯早些时候提出反对PfP0C0源自一个B细胞克隆</h5> <p>以来在我们先前的研究获得几个马伯专门针对PfP0C0从一个鼠标,我们分析了七个马伯的同形像和序列(1 a4, b3、2 c11、1 e5f4 1 f6, 2 g1和2 h1)从这个研究建立他们的亲缘早些时候,如果任何。同形像统计图分析表明,所有的马伯属于IgG1同形像。我们进行rt - pcr和放大产品的重型和轻型链这七个马伯克隆并测序(图<一个href="//www.newsama.com/journals/bmri/2012/695843/fig2/" target="_blank">2</一个>)。观察到,CDR2和CDR3上区域是一样的重链的所有七个克隆。CDR1地区的两个单基地变化1 a4和1 e5f4和3基础2 c11变化催生了一些氨基酸变化的CDR1地区3 7克隆。对于轻链,1 a4和2 c11显示某些基础的变化,而其他五克隆都是相同的。虽然1 a4 CDR3上地区是明显不同的,附近的CDR1和2区域相同。其余地区的IgG1链这些克隆是相同的(数据未显示)。因此,明显在前面获得的克隆研究起源于一个B细胞克隆。这可能是由于一个不寻常的克隆扩张,可能由于公差分解,绝对是一个异常的发病率因为后续分析未能重现我们早些时候获得对PfP0C0马伯克隆(表的结果<一个href="//www.newsama.com/journals/bmri/2012/695843/tab2/" target="_blank">2</一个>)。</p> <div class="partial-carousel-wrapper"> <div class="floats-partial-section"> <div class="floats-partial-content"> <div class="partial-carousel--full-image partial-carousel-1a7cfdda509238984b71e6cee3692d8c"> <div class="partial-carousel--single-image"> <img loading="lazy" alt="" src="https://static.hindawi.com/articles/bmri/volume-2012/695843/figures/695843.fig.002.jpg"> <br> <strong></strong> </div> </div> </div> <div class="floats-partial-middle"> <div class="floats-partial-middle--thumbs"> <div class="partial-carousel-dots-1a7cfdda509238984b71e6cee3692d8c partial-carousel-thumbnail"> <button aria-label="Slide to " class="partial-carousel-dot"><img loading="lazy" alt="" src="https://static.hindawi.com/articles/bmri/volume-2012/695843/thumbnails/695843.fig.002_th.jpg"><br><strong></strong></button> </div> </div> <div class="floats-partial-middle--nav"> <div class="partial-carousel-next-prev-1a7cfdda509238984b71e6cee3692d8c 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p一个n> <a aria-label="View full page" class="caption-partial-url" href="//www.newsama.com/journals/bmri/2012/695843/fig2/" title="" target="_blank"></a> </div> <div class="floats-partial-caption-text"> <table> <tbody> <tr> <td>序列测定anti-PfP0C0马伯在第一项研究中获得的。七马伯获得(在我们的早期研究<一个href="https://static.hindawi.com/articles/bmri/volume-2012/695843/figures/695843/">19</一个>),即1 a4, b3, 2 c11 1 e5f4 1 f6, 2 g1和2 h1测序以确定他们的亲缘。除了一些微小的变化,(红色),所有七马伯都几乎相同,这表明他们已经出现从一个B细胞克隆。</td> </tr> </tbody> </table> </div> </div> </div> </div> <h5 id="sec3.3">3.3。重组PfP0免疫导致小鼠的病理变化</h5> <p>脾收获杂种细胞代过程中,我们注意到轻微的结缔组织纤维化的脾脏免疫(表7<一个href="//www.newsama.com/journals/bmri/2012/695843/tab2/" target="_blank">2</一个>)。加强免疫后的动物开始生病。这逐渐纤维化恶化,11日免疫脾变得很难收获(图<一个href="//www.newsama.com/journals/bmri/2012/695843/fig3/" target="_blank">3</一个>)。明显的脾纤维化早期的研究没有观察到。以来,研究的目的是为了获得PfP0C0马伯,尸检病理检查也没有进行。后期分析的老鼠显示病变的所有主要器官如心脏、肺、肝脏和肾脏(表<一个href="//www.newsama.com/journals/bmri/2012/695843/tab3/" target="_blank">3</一个>)。有趣的是,大脑中没有发现异常。这些研究结果表明,重复与rPfP0导致体液免疫自身免疫反应,可能是因为之间的同源性寄生虫P0 P0和老鼠。大脑是分离血液通过血脑屏障。抗体通常不会跨越这一障碍(<一个href="#B30">32</一个>]。所有主要器官的病理变化观察排除大脑提出自身抗体可能造成的伤害。因此,我们调查了血清对PfP0C0搞笑回应。</p> <div class="floats-partial-section partial-other-wrapper" data-section="tab3"> <div class="floats-partial-footer"> <div class="floats-partial-caption"> <span class="caption-text">表3</年代p一个n> <a aria-label="View full page" class="caption-partial-url" href="//www.newsama.com/journals/bmri/2012/695843/tab3/" title="" target="_blank"></a> </div> <div class="floats-partial-caption-text"> 组织病理学结果调查重复PfP0政府重组后的老鼠。</d我v> <a class="table-thumb-overlay" href="//www.newsama.com/journals/bmri/2012/695843/tab3" target="_blank" aria-label="View full page"></a> </div> </div> <div class="partial-carousel-wrapper"> <div class="floats-partial-section"> <div class="floats-partial-content"> <div class="partial-carousel--full-image partial-carousel-2ad62dfe75e8b2c2d2fb060d50d9386e"> <div class="partial-carousel--single-image"> <img loading="lazy" alt="(一)" src="https://static.hindawi.com/articles/bmri/volume-2012/695843/figures/695843.fig.003a.jpg"> <br> <strong>(一)</年代trong> </div> <div class="partial-carousel--single-image"> <img loading="lazy" alt="(b)" src="https://static.hindawi.com/articles/bmri/volume-2012/695843/figures/695843.fig.003b.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-2ad62dfe75e8b2c2d2fb060d50d9386e partial-carousel-thumbnail"> <button aria-label="Slide to (a) " class="partial-carousel-dot"><img loading="lazy" alt="(一)" src="https://static.hindawi.com/articles/bmri/volume-2012/695843/thumbnails/695843.fig.003a_th.jpg"><br><strong>(一)</年代trong></button> <button aria-label="Slide to (b) " class="partial-carousel-dot"><img loading="lazy" alt="(b)" src="https://static.hindawi.com/articles/bmri/volume-2012/695843/thumbnails/695843.fig.003b_th.jpg"><br><strong>(b)</年代trong></button> </div> </div> <div class="floats-partial-middle--nav"> <div class="partial-carousel-next-prev-2ad62dfe75e8b2c2d2fb060d50d9386e 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p一个n> <a aria-label="View full page" class="caption-partial-url" href="//www.newsama.com/journals/bmri/2012/695843/fig3/" title="" target="_blank"></a> </div> <div class="floats-partial-caption-text"> <table> <tbody> <tr> <td>脾纤维化与重组PfP0重复免疫接种后观察。(一)控制小鼠脾脏。(b)脾鼠标后重复接种重组PfP0(4周和7个月)。箭头指向脾脏。注意减少脾脏的大小和纤维化。组织病理学分析显示的淋巴细胞和脾的广泛替代组织和结缔组织。</td> </tr> </tbody> </table> </div> </div> </div> </div> <h5 id="sec3.4">3.4。重组PfP0诱发Low-Titre,主要Polyreactive血清Anti-PfP0C0响应</h5> <p>从每个月免疫后小鼠血清收集rPfP0 anti-PfP0C0响应进行了测试。血清滴定度保持低蛋白(即使在11日管理表<一个href="//www.newsama.com/journals/bmri/2012/695843/tab2/" target="_blank">2</一个>)。相比之下,high-titre反应得到4或5免疫接种后对各种蛋白质,包括那些显示高度的同源蛋白质如老鼠<我>恶性疟原虫</我>烯醇酶,<我>果蝇</我>translin, TgP0。滴定度较低的血清,再加上不稳定polyreactive杂种细胞,建议诱导anti-PfP0C0反应是polyreactive的可能性。Polyreactive抗体较低亲和力抗体可以结合各种生物分子的自我和non-self-origin [<一个href="#B31">33</一个>,<一个href="#B32">34</一个>]。他们是正常血清成分和最初的免疫反应的重要组成部分。DNP治疗是常用的去除polyreactive抗体在动物不暴露在半抗原(<一个href="#B33">35</一个>,<一个href="#B34">36</一个>]。我们治疗血清DNP-sepharose珠子和确定anti-PfP0C0滴定度的吸附和unadsorbed血清ELISA。DNP导致治疗显著降低anti-PfP0C0血清的反应,表明PfP0免疫诱导很大程度上polyreactive anti-PfP0C0响应。图<一个href="//www.newsama.com/journals/bmri/2012/695843/fig4/" target="_blank">4(一)</一个>显示了一个典型的反应DNP吸附和unadsorbed血清样本。polyreactivity的程度仍然很高(中值32%)即使重复助推器(图<一个href="//www.newsama.com/journals/bmri/2012/695843/fig4/" target="_blank">4 (b)</一个>)。这种polyreactive反应并不局限于一个特定的同形像,但被发现在所有同形像,因为DNP治疗导致显著减少anti-PfP0C0反应在所有同形像(图<一个href="//www.newsama.com/journals/bmri/2012/695843/fig4/" target="_blank">4 (c)</一个>)。我们还检测了血清反应dsDNA, ssDNA和胰岛素。图<一个href="//www.newsama.com/journals/bmri/2012/695843/fig4/" target="_blank">4 (d)</一个>显示一个血清样本的结果。类似的结果为其他样本(数据未显示)。</p> <div class="partial-carousel-wrapper"> <div class="floats-partial-section"> <div class="floats-partial-content"> <div class="partial-carousel--full-image partial-carousel-133dae356cda499876c8f0f334ef4b08"> <div class="partial-carousel--single-image"> <img loading="lazy" alt="(一)" src="https://static.hindawi.com/articles/bmri/volume-2012/695843/figures/695843.fig.004a.jpg"> <br> <strong>(一)</年代trong> </div> <div class="partial-carousel--single-image"> <img loading="lazy" alt="(b)" src="https://static.hindawi.com/articles/bmri/volume-2012/695843/figures/695843.fig.004b.jpg"> <br> <strong>(b)</年代trong> </div> <div class="partial-carousel--single-image"> <img loading="lazy" alt="(c)" src="https://static.hindawi.com/articles/bmri/volume-2012/695843/figures/695843.fig.004c.jpg"> <br> <strong>(c)</年代trong> </div> <div class="partial-carousel--single-image"> <img loading="lazy" alt="(d)" src="https://static.hindawi.com/articles/bmri/volume-2012/695843/figures/695843.fig.004d.jpg"> <br> <strong>(d)</年代trong> </div> <div class="partial-carousel--single-image"> <img loading="lazy" alt="(e)" src="https://static.hindawi.com/articles/bmri/volume-2012/695843/figures/695843.fig.004e.jpg"> <br> <strong>(e)</年代trong> </div> </div> </div> <div class="floats-partial-middle"> <div class="floats-partial-middle--thumbs"> <div class="partial-carousel-dots-133dae356cda499876c8f0f334ef4b08 partial-carousel-thumbnail"> <button aria-label="Slide to (a) " class="partial-carousel-dot"><img loading="lazy" alt="(一)" src="https://static.hindawi.com/articles/bmri/volume-2012/695843/thumbnails/695843.fig.004a_th.jpg"><br><strong>(一)</年代trong></button> <button aria-label="Slide to (b) " class="partial-carousel-dot"><img loading="lazy" alt="(b)" src="https://static.hindawi.com/articles/bmri/volume-2012/695843/thumbnails/695843.fig.004b_th.jpg"><br><strong>(b)</年代trong></button> <button aria-label="Slide to (c) " class="partial-carousel-dot"><img loading="lazy" alt="(c)" src="https://static.hindawi.com/articles/bmri/volume-2012/695843/thumbnails/695843.fig.004c_th.jpg"><br><strong>(c)</年代trong></button> <button aria-label="Slide to (d) " class="partial-carousel-dot"><img loading="lazy" alt="(d)" src="https://static.hindawi.com/articles/bmri/volume-2012/695843/thumbnails/695843.fig.004d_th.jpg"><br><strong>(d)</年代trong></button> <button aria-label="Slide to (e) " class="partial-carousel-dot"><img loading="lazy" alt="(e)" src="https://static.hindawi.com/articles/bmri/volume-2012/695843/thumbnails/695843.fig.004e_th.jpg"><br><strong>(e)</年代trong></button> </div> </div> <div class="floats-partial-middle--nav"> <div class="partial-carousel-next-prev-133dae356cda499876c8f0f334ef4b08 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p一个n> <a aria-label="View full page" class="caption-partial-url" href="//www.newsama.com/journals/bmri/2012/695843/fig4/" title="" target="_blank"></a> </div> <div class="floats-partial-caption-text"> <table> <tbody> <tr> <td>Polyreactive血清anti-PfP0C0反应诱导后重复与rPfP0但不是BSA-PfP0C0免疫接种。(a)小鼠的血清注射重组PfP0治疗与否与DNP-sepharose珠子。Anti-PfP0C0滴定度治疗前后测定ELISA。代表的例子anti-PfP0C0 DNP的反应吸附(空圈)和unadsorbed(满圈)血清。误差线代表三个读数的SEM。(b)小鼠接种4周和7月rPfP0注射。整除的血清处理DNP-sepharose珠子polyreactive抗体吸附。酒吧图表描述多个免疫后小鼠的血清polyreactivity百分比表示。误差线代表3血清的SEM。(c)箱形图显示第25和第75百分位数,加上中间,胡须显示最小和最大的区别,圆圈代表局外人,ELISA OD反应的DNP unadsorbed (U)和吸附(A)与重组PfP0 21小鼠血清的免疫;<我>μ</我>(IgM),<我>γ</我>1 (IgG1)<我>γ</我>2 (IgG2a),<我>γ</我>2 b (IgG2b),<我>γ</我>3 (IgG3),<我>α</我>(IgA)。获得的显著值成对Wilcoxan符号秩检验表示。(d) Autoreactivity代表血清样本的牛胰岛素(封闭的圆),dsDNA(开环),和ssDNA rPfP0(封闭的三角形)的小鼠免疫。红线代表未接受免疫接种的血清的反应控制在最低稀释(1:1000)。误差线代表三个读数的SEM。与其他血清也获得类似的结果。(e)小鼠接种BSA-PfP0C0,血清治疗与否与DNP-sepharose珠子。Anti-PfP0C0滴定度治疗前后ELISA的决心。代表的例子anti-PfP0C0 DNP的反应吸附(空圈)和unadsorbed(满圈)血清。误差线代表三个读数的SEM。</td> </tr> </tbody> </table> </div> </div> </div> </div> <h5 id="sec3.5">3.5。疟疾感染也会导致Low-Titre,主要Polyreactive血清Anti-PfP0和Anti-PfP0C0响应</h5> <p>我们希望确定简单的疟疾患者的血清也显示出类似的PfP0 polyreactive反应。蛋白质是高度保守的<我>恶性疟原虫</我>。在报告的13株PlasmoDB [<一个href="#B35">37</一个>),DNA序列是相同的除了一个同义突变株(图<一个href="//www.newsama.com/journals/bmri/2012/695843/fig5/" target="_blank">5</一个>)。PfP0也大量表达表面裂殖子(<一个href="#B17">18</一个>]。虽然我们通常看到高架抗体反应PfP0疟疾免疫成人患者相比(<一个href="#B17">18</一个>),我们没有评估polyreactive组件。我们测试了从免疫血清的成年人也为anti-PfP0疟疾患者无并发症和anti-PfP0C0抗体。早些时候在协议与我们的结果,免疫的成年人,而不是病人,显示响应PfP0升高(图<一个href="//www.newsama.com/journals/bmri/2012/695843/fig6/" target="_blank">6(一)</一个>,<年代vg height="11.0625" id="M8" style="vertical-align:-0.30096pt;width:56.150002px;" version="1.1" viewbox="0 0 56.150002 11.0625" width="56.150002" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,11.0625)"> <g transform="translate(72,-63.15)"> <text transform="matrix(1,0,0,-1,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代p一个n> <tspan style="font-size: 12.50px; " x="10.890113" y="0"> <</t年代p一个n> <tspan style="font-size: 12.50px; " x="22.930502" y="0"> 0</t年代p一个n> <tspan style="font-size: 12.50px; " x="29.182001" y="0"> 。</t年代p一个n> <tspan style="font-size: 12.50px; " x="32.307751" y="0"> 0</t年代p一个n> <tspan style="font-size: 12.50px; " x="38.559254" y="0"> 1</t年代p一个n> </text> </g> </g> </svg>)。分析响应polyreactivity PfP0显示病人的血清高polyreactive(图<一个href="//www.newsama.com/journals/bmri/2012/695843/fig6/" target="_blank">6 (b)</一个>;中值44.8%)。相比之下,从免疫成年人表现出最小polyreactivity血清蛋白(<年代vg height="10.9125" id="M9" style="vertical-align:-0.17555pt;width:63.962502px;" version="1.1" viewbox="0 0 63.962502 10.9125" width="63.962502" 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p一个n> <tspan style="font-size: 12.50px; " x="10.890113" y="0"> =</t年代p一个n> <tspan style="font-size: 12.50px; " x="22.930502" y="0"> 0</t年代p一个n> <tspan style="font-size: 12.50px; " x="29.182001" y="0"> 。</t年代p一个n> <tspan style="font-size: 12.50px; " x="32.307751" y="0"> 0</t年代p一个n> <tspan style="font-size: 12.50px; " x="38.559254" y="0"> 0</t年代p一个n> <tspan style="font-size: 12.50px; " x="44.810753" y="0"> 1</t年代p一个n> </text> </g> </g> </svg>;中值13.9%)。类似的结果PfP0C0(数据没有显示)。</p> <div class="partial-carousel-wrapper"> <div class="floats-partial-section"> <div class="floats-partial-content"> <div class="partial-carousel--full-image partial-carousel-e370b86159a66e59b54fedbbe945a119"> <div class="partial-carousel--single-image"> <img loading="lazy" alt="" src="https://static.hindawi.com/articles/bmri/volume-2012/695843/figures/695843.fig.005.jpg"> <br> <strong></strong> </div> </div> </div> <div class="floats-partial-middle"> <div class="floats-partial-middle--thumbs"> <div class="partial-carousel-dots-e370b86159a66e59b54fedbbe945a119 partial-carousel-thumbnail"> <button aria-label="Slide to " class="partial-carousel-dot"><img loading="lazy" alt="" src="https://static.hindawi.com/articles/bmri/volume-2012/695843/thumbnails/695843.fig.005_th.jpg"><br><strong></strong></button> </div> </div> <div class="floats-partial-middle--nav"> <div class="partial-carousel-next-prev-e370b86159a66e59b54fedbbe945a119 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p一个n> <a aria-label="View full page" class="caption-partial-url" href="//www.newsama.com/journals/bmri/2012/695843/fig5/" title="" target="_blank"></a> </div> <div class="floats-partial-caption-text"> <table> <tbody> <tr> <td>DNA序列比对的P0<我>恶性疟原虫</我>菌株显示同义突变(黄色标记)在圣卢西亚的压力。其余的序列是相同的菌株。</td> </tr> </tbody> </table> </div> </div> </div> </div> <div class="partial-carousel-wrapper"> <div class="floats-partial-section"> <div class="floats-partial-content"> <div class="partial-carousel--full-image partial-carousel-5045ce3f7e1b5f8c5cb9333c24f25d58"> <div class="partial-carousel--single-image"> <img loading="lazy" alt="(一)" src="https://static.hindawi.com/articles/bmri/volume-2012/695843/figures/695843.fig.006a.jpg"> <br> <strong>(一)</年代trong> </div> <div class="partial-carousel--single-image"> <img loading="lazy" alt="(b)" src="https://static.hindawi.com/articles/bmri/volume-2012/695843/figures/695843.fig.006b.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-5045ce3f7e1b5f8c5cb9333c24f25d58 partial-carousel-thumbnail"> <button aria-label="Slide to (a) " class="partial-carousel-dot"><img loading="lazy" alt="(一)" src="https://static.hindawi.com/articles/bmri/volume-2012/695843/thumbnails/695843.fig.006a_th.jpg"><br><strong>(一)</年代trong></button> <button aria-label="Slide to (b) " class="partial-carousel-dot"><img loading="lazy" alt="(b)" src="https://static.hindawi.com/articles/bmri/volume-2012/695843/thumbnails/695843.fig.006b_th.jpg"><br><strong>(b)</年代trong></button> </div> </div> <div class="floats-partial-middle--nav"> <div class="partial-carousel-next-prev-5045ce3f7e1b5f8c5cb9333c24f25d58 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p一个n> <a aria-label="View full page" class="caption-partial-url" href="//www.newsama.com/journals/bmri/2012/695843/fig6/" title="" target="_blank"></a> </div> <div class="floats-partial-caption-text"> <table> <tbody> <tr> <td>Polyreactive血清anti-PfP0C0响应简单的疟疾患者中观察到,但在免疫成年人生活在高度流行地区。(一)箱形图显示第25和第75百分位数,加上中间,胡须显示最小和最大的区别,圆圈代表的离群值anti-PfP0简单的疟疾病人的血清反应(<年代vg height="11.0375" id="M10" style="vertical-align:-0.27588pt" version="1.1" viewbox="0 0 42.912498 11.0375" width="42.912498" 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,-71.95,63.5)"> <tspan style="font-size: 12.50px; " x="0" y="0"> </t年代p一个n> <tspan style="font-size: 12.50px; " x="9.6773224" y="0"> =</t年代p一个n> <tspan style="font-size: 12.50px; " x="21.71771" y="0"> 4</t年代p一个n> <tspan style="font-size: 12.50px; " x="27.969212" y="0"> 9</t年代p一个n> </text> </g> </g> </svg>)和免疫成人(<年代vg height="10.9125" id="M11" style="vertical-align:-0.17555pt" version="1.1" viewbox="0 0 42.912498 10.9125" width="42.912498" 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p一个n> <tspan style="font-size: 12.50px; " x="9.6773224" y="0"> =</t年代p一个n> <tspan style="font-size: 12.50px; " x="21.71771" y="0"> 3</t年代p一个n> <tspan style="font-size: 12.50px; " x="27.969212" y="0"> 0</t年代p一个n> </text> </g> </g> </svg>在ELISA)决定。(b)箱形图显示第25和第75百分位数,加上中间,胡须显示最小和最大的区别,圆圈代表的离群值% polyreactivity anti-PfP0病人的血清反应和免疫的成年人。DNP-sepharose珠子的血清治疗与否,和anti-PfP0滴定度治疗前后在ELISA测定% polyreactivity决定。</td> </tr> </tbody> </table> </div> </div> </div> </div> <p>Polyreactive自身抗体已报告<我>Plasmodium-chabaudi</我>来华的老鼠(<一个href="#B36">38</一个>]。在临床上发现的自身抗体保护地区的人居住在疟疾省级行政区呈高度流行)类似于那些出现在疾病如系统性红斑狼疮、类风湿关节炎、干燥综合征、多发性肌炎、硬皮病、桥本甲状腺炎。这些可以绑定双和单链DNA,红细胞,免疫球蛋白,核糖核蛋白和烯醇酶。然而,anti-thyroglobulin抗体,autoreactive中B细胞和正常的人,在这样一个人口不增强,这表明这不是一个随机的问题对守恒的抗原非特异性多克隆激活B细胞(<一个href="#B17">18</一个>,<一个href="#B23">25</一个>,<一个href="#B37">39</一个>,<一个href="#B38">40</一个>]。不太可能相同的PfP0宿主蛋白质负责观察polyreactive响应自重复免疫与Pf烯醇酶或牛血清白蛋白耦合PfP0C0 (BSA-PfP0C0)未能诱导polyreactive响应。有趣的是,虽然具体,BSA-PfP0C0政府没有诱导高滴定度anti-PfP0C0响应(滴定度<我>~</我>2<年代vg height="14.375" id="M12" style="vertical-align:-0.3135pt;width:31.85px;" version="1.1" viewbox="0 0 31.85 14.375" width="31.85" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,14.375)"> <g transform="translate(72,-60.5)"> <text transform="matrix(1,0,0,-1,-71.95,60.86)"> <tspan style="font-size: 12.50px; " x="0" y="0"> ×</t年代p一个n> <tspan style="font-size: 12.50px; " x="8.0019197" y="0"> 1</t年代p一个n> <tspan style="font-size: 12.50px; " x="14.25342" y="0"> 0</t年代p一个n> </text> <text transform="matrix(1,0,0,-1,-51.45,66.03)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 4</t年代p一个n> </text> </g> </g> </svg>,图<一个href="//www.newsama.com/journals/bmri/2012/695843/fig4/" target="_blank">4 (e)</一个>)。然而,这种反应是autoreactive,因为血清反应鼠标P0C0,尽管十倍低浓度(滴定度~ 2<年代vg height="14.375" id="M13" style="vertical-align:-0.3135pt;width:31.85px;" version="1.1" viewbox="0 0 31.85 14.375" width="31.85" xmlns="http://www.w3.org/2000/svg"> <g transform="matrix(1.25,0,0,-1.25,0,14.375)"> <g transform="translate(72,-60.5)"> <text transform="matrix(1,0,0,-1,-71.95,60.86)"> <tspan style="font-size: 12.50px; " x="0" y="0"> ×</t年代p一个n> <tspan style="font-size: 12.50px; " x="8.0019197" y="0"> 1</t年代p一个n> <tspan style="font-size: 12.50px; " x="14.25342" y="0"> 0</t年代p一个n> </text> <text transform="matrix(1,0,0,-1,-51.45,66.03)"> <tspan style="font-size: 8.75px; " x="0" y="0"> 3</t年代p一个n> </text> </g> </g> </svg>数据未显示)。因此,潜在autoreactive抗原决定基耦合到载体蛋白未能产生polyreactive应答,但包含61 - 316年的重组蛋白氨基酸诱导low-titre, polyreactive响应。这表明能力诱导polyreactivity可能在于61−300地区的蛋白质。也有可能蛋白质的构象是polyreactivity感应的一个重要因素,或者rPfP0就像一个B细胞分裂素。还需要进一步的调查来确定一个特定的区域和/或蛋白质的构象结构负责诱导polyreactive响应。</p> <p>正常的人类血清含天然自身抗体可以识别自体抗原(<一个href="#B39">41</一个>]。分析人类单克隆抗体来源于正常外周血B细胞表明天然自身抗体polyreactive和表达生殖系免疫球蛋白可变区基因很少或根本没有体细胞突变(<一个href="#B40">42</一个>,<一个href="#B41">43</一个>),虽然在affinity-matured polyreactivity也被观察到抗体(<一个href="#B42">44</一个>]。平衡能力采用多种构象状态允许polyreactive抗体绑定多个结构无关抗原(<一个href="#B43">45</一个>]。Polyreactive抗体诱导的小鼠模型已报告疟疾(<一个href="#B36">38</一个>]。我们表明,免疫parasite-derived蛋白质也能导致polyreactive响应。有趣的是,我们发现人们患有疟疾也表现出PfP0 polyreactive反应。这polyreactive反应是局限于病人,因为成人免疫血清显示一个相对nonpolyreactive反应的蛋白质。之前我们已经表明,PfP0表达表面裂殖子(<一个href="#B17">18</一个>]。因此,它可能是暴露在低水平的蛋白质(如免疫的情况下会发生的地方性成年人)结果在特定反应的蛋白质,和这个特定的反应疾病预防疟疾。暴露于高剂量的蛋白质(例如,在活动期间疟疾疾病或免疫协议),另一方面,可能导致polyreactive响应。还需要进一步的调查来看看低剂量的PfP0有或没有一个强有力的辅助导致特定anti-PfP0反应。</p> <p>抗体有关键作用的控制疟疾感染。调理素作用的寄生虫抗体蛋白质表达裂殖子或感染的红细胞表面有助于它们被巨噬细胞清除和最终的破坏(<一个href="#B44">46</一个>]。疟疾寄生虫已经证明可以破坏宿主的免疫系统以多种方式包括抗原变异和抗原的多态性,干扰树突状细胞成熟,诱导细胞凋亡在内存中B和T细胞(<一个href="#B45">47</一个>- - - - - -<一个href="#B48">50</一个>]。在这里,我们表明,守恒,parasite-derived宿主蛋白诱导的体液反应。表达倾向或分泌的抗原诱导弱polyreactive体液反应可能是一个加强寄生虫生存机制。</p> <h4 id="abbreviations">缩写</h4> <table class="gloss-abbr" style="font-size:12px"> <tbody> <tr> <td align="left">PfP0:</td> <td align="left"><i>恶性疟原虫</我>P0</td> </tr> <tr> <td align="left">rPfP0:</td> <td align="left">重组PfP0</td> </tr> <tr> <td align="left">PfP0C0:</td> <td align="left">PfP0 Carboxy-terminal 16个氨基酸</td> </tr> <tr> <td align="left">系统性红斑狼疮:</td> <td align="left">系统性红斑狼疮</td> </tr> <tr> <td align="left">马伯:</td> <td align="left">单克隆抗体</td> </tr> <tr> <td align="left">DNP:</td> <td align="left">Dinitrophenyl</td> </tr> <tr> <td align="left">TgP0:</td> <td align="left"><i>刚地弓形虫</我>P0</td> </tr> <tr> <td align="left">BSA-PfP0C0:</td> <td align="left">牛血清白蛋白PfP0C0耦合。</td> </tr> </tbody> </table> <h4 id="acknowledgments">确认</h4> <p>作者欣然承认博士Pierre-Andre Cazenave的批判阅读手稿。他们也感谢Das和n金达尔博士的输入。本研究使用资金的原子能,印度政府。美国帕沙克和k . 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fill-rule="evenodd" clip-rule="evenodd" d="M14.7071 1.29289C14.5196 1.10536 14.2652 1 14 1H6C4.34315 1 3 2.34315 3 4V20C3 21.6569 4.34315 23 6 23H18C19.6569 23 21 21.6569 21 20V8C21 7.73478 20.8946 7.48043 20.7071 7.29289L14.7071 1.29289ZM6 3H13.5858L19 8.41421V20C19 20.5523 18.5523 21 18 21H6C5.44772 21 5 20.5523 5 20V4C5 3.44772 5.44772 3 6 3Z" fill="currentColor"></path> </svg></span><span>下载引用</年代p一个n></span><span role="img" class="anticon ButtonGroup_buttonGroupWrapperIcon__CFikg"> <svg width="1em" height="1em" viewbox="0 0 20 22"> <defs> <clippath> <path fill-rule="evenodd" clip-rule="evenodd" d="M3,22a3,3,0,0,1-3-3V16a1,1,0,0,1,2,0v3a1,1,0,0,0,1,1H17a1,1,0,0,0,1-1V16a1,1,0,1,1,2,0v3a3,3,0,0,1-3,3Zm6.288-6.3-4-4a1,1,0,0,1,1.414-1.414L9,12.586V1a1,1,0,0,1,2,0V12.586l2.293-2.293a1,1,0,0,1,1.414,1.414l-4,4a1,1,0,0,1-1.423,0Z" fill="currentColor"></path> </clippath> </defs> <g> <path fill-rule="evenodd" clip-rule="evenodd" d="M3,22a3,3,0,0,1-3-3V16a1,1,0,0,1,2,0v3a1,1,0,0,0,1,1H17a1,1,0,0,0,1-1V16a1,1,0,1,1,2,0v3a3,3,0,0,1-3,3Zm6.288-6.3-4-4a1,1,0,0,1,1.414-1.414L9,12.586V1a1,1,0,0,1,2,0V12.586l2.293-2.293a1,1,0,0,1,1.414,1.414l-4,4a1,1,0,0,1-1.423,0Z" fill="currentColor"></path> </g> </svg></span></a> <div class="ant-collapse ant-collapse-icon-position-end articleToolbarOtherFormats_otherFormatsCollapse__VHaOL"> <div class="ant-collapse-item"> <div class="ant-collapse-header" aria-expanded="false" aria-disabled="false" role="button" tabindex="0"> <div class="ant-collapse-expand-icon"> <span role="img" class="anticon ant-collapse-arrow"> <svg width="1em" height="1em" viewbox="0 0 32 32" fill="none"> <path fill-rule="evenodd" clip-rule="evenodd" d="M17.773 23.453l11.2-11.265a1.918 1.918 0 000-2.641 1.75 1.75 0 00-2.542 0l-9.929 10.101-9.933-10.1a1.75 1.75 0 00-2.542 0 1.919 1.919 0 000 2.64L15.23 23.453c.352.365.811.547 1.271.547.46 0 .92-.182 1.271-.547z" fill="currentColor"></path> </svg></span> </div> <span class="ant-collapse-header-text"><span><span role="img" class="anticon articleToolbarOtherFormats_atofDownloadIcon__YRM5T"> <svg width="1em" height="1em" viewbox="0 0 20 22"> <defs> <clippath> <path fill-rule="evenodd" clip-rule="evenodd" d="M3,22a3,3,0,0,1-3-3V16a1,1,0,0,1,2,0v3a1,1,0,0,0,1,1H17a1,1,0,0,0,1-1V16a1,1,0,1,1,2,0v3a3,3,0,0,1-3,3Zm6.288-6.3-4-4a1,1,0,0,1,1.414-1.414L9,12.586V1a1,1,0,0,1,2,0V12.586l2.293-2.293a1,1,0,0,1,1.414,1.414l-4,4a1,1,0,0,1-1.423,0Z" fill="currentColor"></path> </clippath> </defs> <g> <path fill-rule="evenodd" clip-rule="evenodd" d="M3,22a3,3,0,0,1-3-3V16a1,1,0,0,1,2,0v3a1,1,0,0,0,1,1H17a1,1,0,0,0,1-1V16a1,1,0,1,1,2,0v3a3,3,0,0,1-3,3Zm6.288-6.3-4-4a1,1,0,0,1,1.414-1.414L9,12.586V1a1,1,0,0,1,2,0V12.586l2.293-2.293a1,1,0,0,1,1.414,1.414l-4,4a1,1,0,0,1-1.423,0Z" fill="currentColor"></path> </g> </svg></span><span>下载其他格式</年代p一个n></span></span> </div> </div> </div> <a href="//www.newsama.com/reprints/695843/confirm" class="ButtonGroup_buttonGroupWrapper__Rqhy0" role="button" type="ghost" aria-label="Order printed copies" tabindex="0" unselectable="on" target="_blank"><span class="ButtonGroup_leftGroup__FJAmS"><span role="img" class="anticon ButtonGroup_buttonGroupWrapperIcon__CFikg"> <svg width="1em" height="1em" viewbox="0 0 24 24" fill="none" xmlns="http://www.w3.org/2000/svg"> <path fill-rule="evenodd" clip-rule="evenodd" d="M7.41667 1H18.6667C19.1269 1 19.5 1.44772 19.5 2V22C19.5 22.5523 19.1269 23 18.6667 23H7.41667C5.80584 23 4.5 21.433 4.5 19.5V4.5C4.5 2.567 5.80584 1 7.41667 1ZM6.16667 16.3368V4.5C6.16667 3.67157 6.72631 3 7.41667 3H17.8333V16H7.41667C6.96933 16 6.54552 16.1208 6.16667 16.3368ZM17.8333 18H7.41667C6.72631 18 6.16667 18.6716 6.16667 19.5C6.16667 20.3284 6.72631 21 7.41667 21H17.8333V18Z" fill="currentColor"></path> </svg></span><span>订单打印副本</年代p一个n></span><span role="img" class="anticon ButtonGroup_buttonGroupWrapperIcon__CFikg"> <svg width="1em" height="1em" viewbox="0 0 18 14"> <defs> <clippath id="a"> <path d="M10.293,13.707a1,1,0,0,1,0-1.414L14.586,8H1A1,1,0,0,1,1,6H14.586L10.293,1.707A1,1,0,0,1,11.707.293l6,6a1,1,0,0,1,.172.231h0l.01.019,0,.005.007.014.006.012,0,.008.008.018v0a1,1,0,0,1-.009.817l0,0L17.9,7.44l0,.009-.005.011-.007.013,0,.008-.008.015,0,.005-.01.016,0,0-.011.017,0,0-.012.018,0,0-.012.017,0,0L17.8,7.6l0,0-.011.014,0,.006-.01.012-.009.011-.006.007-.015.017h0l-.04.042-6,6a1,1,0,0,1-1.414,0Z" transform="translate(3 5)"></path> </clippath> </defs> <g transform="translate(-3 -5)"> <path d="M10.293,13.707a1,1,0,0,1,0-1.414L14.586,8H1A1,1,0,0,1,1,6H14.586L10.293,1.707A1,1,0,0,1,11.707.293l6,6a1,1,0,0,1,.172.231h0l.01.019,0,.005.007.014.006.012,0,.008.008.018v0a1,1,0,0,1-.009.817l0,0L17.9,7.44l0,.009-.005.011-.007.013,0,.008-.008.015,0,.005-.01.016,0,0-.011.017,0,0-.012.018,0,0-.012.017,0,0L17.8,7.6l0,0-.011.014,0,.006-.01.012-.009.011-.006.007-.015.017h0l-.04.042-6,6a1,1,0,0,1-1.414,0Z" transform="translate(3 5)" fill="currentColor"></path> </g> </svg></span></a> <div class="articleToolbarStatistics_articleToolbarStatistics__8_woN"> <div class="articleToolbarStatistics_column__R2GqD"> <div> <div> <span>的观点</年代p一个n> <div class="articleToolbarStatistics_amount__vJIDp"> 1323年</d我v> </div> <div> <span>下载</年代p一个n> <div class="articleToolbarStatistics_amount__vJIDp"> 1137年</d我v> </div> </div> </div> <div class="articleToolbarStatistics_column__R2GqD articleToolbarStatistics_dimensions__pe7pO"> <div> 引用</d我v> <span class="__dimensions_badge_embed__ articleToolbarStatistics_circle__p2dSc" data-doi="10.1155/2012/695843" data-style="small_circle"></span> </div> </div> <ul class="articleToolbarSocials_articleToolbarSocials__g02HH"> <li><a href="https://twitter.com/share?url=https://doi.org/10.1155/2012/695843&via=Hindawi" unselectable="on" title="" rel="noopener noreferrer" target="_blank"><span role="img" class="anticon"> <svg xmlns="http://www.w3.org/2000/svg" width="1em" height="1em" viewbox="126.444 2.281 589 589"> <circle 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