本文選題：丙型肝炎病毒 + 抗體親和力　； 參考：《大連醫(yī)科大學(xué)》2016年博士論文

【摘要】：背景:丙型肝炎病毒(Hepatitis C Virus,HCV)是輸血后以及散發(fā)性肝炎的主要病原,是世界性的公共衛(wèi)生難題。全世界約有1億7千萬HCV血清學(xué)陽性的患者,面臨著轉(zhuǎn)變成肝硬化、肝癌的風(fēng)險。盡管HCV能刺激機體產(chǎn)生有效的免疫反應(yīng),但80%的HCV感染者會進(jìn)展成慢性丙肝患者,只有20%患者能有效清除病毒,自行恢復(fù)且不留任何后遺癥。大多數(shù)HCV慢性感染患者體內(nèi)能產(chǎn)生針對不同HCV病毒蛋白的抗體,而且在患者血清中能檢測到這些抗體的存在。顯然,HCV感染的宿主免疫反應(yīng)的類型和強度可能對其預(yù)后用著重要作用。HCV抗體檢測對HCV診斷有重要價值,中和抗體能直接作用于HCV病毒,但一般認(rèn)為通常在HCV感染者中所檢測到的抗體是針對HCr43蛋白(HCV非結(jié)構(gòu)區(qū)NS3及核心區(qū)的編碼產(chǎn)物)、c100-3抗原(HCV非結(jié)構(gòu)區(qū)NS3、NS4的編碼產(chǎn)物)的抗體,為非中和抗體,因此,不能通過檢測HCV抗體準(zhǔn)確判定HCV感染者的免疫狀態(tài)。我們在對乙型肝炎anti-HBc親和力與HBV感染的聯(lián)系中發(fā)現(xiàn)同為非中和抗體,但anti-HBc親和力與HBV感染的預(yù)后關(guān)系密切;也有研究證明抗體親和力高低能準(zhǔn)確反映巨細(xì)胞病毒感染的活動狀況。測定HCV抗體親和力有可能較為準(zhǔn)確的反映HCV感染者的免疫狀況,對判定HCV感染的現(xiàn)狀和結(jié)局提供有價值的信息。抗體的總活性取決于抗體蛋白的含量及其與抗原間的結(jié)合活性(親和力)。而目前臨床實驗室hcv抗體的檢測只檢測抗體的總活性,并未涉及抗體蛋白的含量和抗體親和力的檢測,本研究將hcv抗體總活性解析成抗體蛋白量和抗體親和力,試圖利用常規(guī)的hcv抗體總活性的檢測系統(tǒng),參照乙型肝炎anti-hbc親和力的檢測原理來建立hcv抗體親和力的檢測方法,并探討丙型肝炎病毒抗體親和力、總活性及物質(zhì)量與病毒載量、機體損傷程度以及疾病不同階段變化的動力學(xué)聯(lián)系。近十年對hla和hcv感染持續(xù)性及清除的研究非常多,機體對病毒表位的免疫反應(yīng)取決于抗原遞呈細(xì)胞加工和遞呈抗原表位的能力,以及免疫細(xì)胞識別這些抗原表位的能力,而這些功能是由hla分子遺傳決定的,因而推測hla類型可影響hcv感染結(jié)局。hla-i類等位基因與hcv感染的自限性轉(zhuǎn)歸之間存在很強的相關(guān)性,例如hla-i類等位基因a3、b27和cw*01均與病毒清除相關(guān),而b8則與病毒的持續(xù)性感染相關(guān)。ns3區(qū)域的一個表位對hla-dr具有高度親和性,提示hla-Ⅱ類分子也與病毒清除有關(guān)。某些hla-Ⅱ類等位基因也與hcv感染的結(jié)局相關(guān),與病毒清除最為高度相關(guān)的hla-Ⅱ類等位基因是dqb1*0301基因和drb1*1101。然而,這些研究結(jié)果并不完全一致,甚至相互矛盾。目的:采用抗體多維數(shù)據(jù)分析,建立hcv抗體親和力的檢測方法,并探討丙型肝炎病毒抗體親和力、物質(zhì)量及總活性動力學(xué)變化及其與病毒量、機體損傷程度以及疾病不同階段的聯(lián)系。hcv感染患者h(yuǎn)la-a,hla-b,hla-drb1基因型別與疾病過程的聯(lián)系以及其作用機制。方法:1、采用重組乙型肝炎疫苗反復(fù)三次皮下注射免疫兔子,第一次注射一周后采集兔子血清,獲得低親和力抗體動物血清;第三次注射兩周后采集兔子血清,獲得高親和力抗體動物血清,倍比稀釋血清,采用雙抗原夾心酶聯(lián)免疫吸附實驗測定anti-hbs。隨機收集臨床診斷為hcv感染患者血清106例,采用化學(xué)發(fā)光微粒子免疫檢測法測定hcv抗體,pcr-熒光探針法檢測hcv-rna,同時檢測alt、ast、alb等臨床常用檢測指標(biāo)。根據(jù)alt、ast水平以及hcv-rna水平各分三組,比較分析組間抗體親和力、抗體總活性及抗體物質(zhì)量的變化。2、隨機收集臨床診斷為hcv感染患者血清328例,采用化學(xué)發(fā)光微粒子免疫檢測法測定hcv抗體,pcr-熒光探針法檢測hcv-rna,同時檢測alb。根據(jù)疾病階段分為慢性肝炎組和肝硬化組,慢性肝炎組又根據(jù)患者alb和hcv-rna水平分為:alb正常hcv-rna陰性組(好轉(zhuǎn)恢復(fù)階段)和其他組(進(jìn)展階段)。分析比較組間抗體親和力、抗體物質(zhì)量及抗體總活性的變化。3、隨機收集臨床診斷為hcv感染患者血清104例及健康對照200例,采用化學(xué)發(fā)光微粒子免疫檢測法測定hcv抗體,pcr-熒光探針法檢測hcv-rna,同時檢測血清alb水平,采用測序方法(sequencebasedtyping,pcr-sbt)進(jìn)行hla基因型的鑒定。比較分析不同hla型別間alb水平、抗體親和力、抗體物質(zhì)量及抗體總活性的變化。4、采用網(wǎng)上搜索數(shù)據(jù)庫結(jié)合discoverystudio(ds)軟件來分析預(yù)測ns3和hla-drb1*09,hla-a*02,hla-a*33,hla-b*58,hla-drb1*07,hla-drb1*13這6種hla蛋白分子之間的相互作用。數(shù)據(jù)庫包括美國國立醫(yī)學(xué)圖書館文獻(xiàn)檢索系統(tǒng)ncbi,蛋白質(zhì)結(jié)構(gòu)數(shù)據(jù)庫pdb以及prosite數(shù)據(jù)庫。結(jié)果:1、雌兔第1次免疫后血清抗體親和力為0.522,第2次為0.826,第3次為0.896;雄兔第1次免疫后血清抗體親和力為0.816,第2次為0.846,第3次為0.972,均呈逐漸升高趨勢,與抗體親和力成熟規(guī)律一致。2、alt、ast正常組的抗體物質(zhì)量明顯低于任一異常組、均異常組(p0.05),而抗體親和力則明顯高于任一異常組、均異常組(p0.05)。抗體總活性在三組中比較,均沒有顯著性差異(p0.05)。3、根據(jù)hcv-rna水平,將alt、ast均正常組(53例)進(jìn)一步分組為hcv-rna陰性組和hcv-rna陽性組。hcv-rna陰性組的抗體總活性、抗體物質(zhì)量均明顯低于hcv-rna陽性組(p0.05),而抗體親和力卻明顯高于hcv-rna陽性組(p0.05)。4、hcv-rna陰性組的抗體總活性、抗體物質(zhì)量均明顯低于低病毒載量、高病毒載量組(p0.05),而抗體親和力則明顯高于低病毒載量、高病毒載量組(p0.05)。5、以hcv-rna陽性為因變量,抗體親和力、抗體物質(zhì)量和抗體總活性為自變量,進(jìn)行l(wèi)ogistic回歸分析,hcv-rna水平與抗體親和力呈負(fù)相關(guān)(p0.05)。6、alb正常hcv-rna陰性組的抗體親和力明顯高于慢性肝炎其他組和肝硬化組(p0.05),而抗體物質(zhì)量明顯低于慢性肝炎其他組和肝硬化組(p0.05),抗體總活性在三組中比較沒有顯著性差異(p0.05)。7、抗體親和力和抗體物質(zhì)量的roc曲線下面積分別是0.816、0.811,均顯示了較高的診斷效能,明顯高于傳統(tǒng)的抗體檢測(roc曲線下面積為0.581)�？贵w親和力對于區(qū)分丙肝感染進(jìn)展階段(hcv-rna陽性)和好轉(zhuǎn)階段(hcv-rna陰性)的最佳診斷臨界點為0.873,抗體親和力越高,病毒復(fù)制越少。8、alb正常hcv-rna陰性組中,高抗體親和力(≥0.873)的比例明顯高于慢性肝炎其他組和肝硬化組(p0.05)。9、hcv-rna(+)的血清被含有高親和力抗體的血清中和后,lgrna明顯低于中和前的水平(p0.05)。10、在hcv患者和健康對照組中鑒定出8種hla型別具有顯著性差異(p0.05),分別是hla-a*02,hla-b*39,hla-drb1*09,hla-drb1*11,hla-a*33,hla-b*58,hla-drb1*07,hla-drb1*13。其中hla-a*02,hla-b*39,hla-drb1*09,hla-drb1*11在hcv患者中陽性率明顯低于健康對照組,而hla-a*33,hla-b*58,hla-drb1*07,hla-drb1*13則明顯高于健康對照組(p0.05),提示hla-a*02,hla-b*39,hla-drb1*09,hla-drb1*11為丙肝感染的抵抗基因,而hla-a*33,hla-b*58,hla-drb1*07,hla-drb1*13則是丙肝感染的敏感基因。11、在上述8種hla型別中,血清alb水平在hla-a*02,hla-a*33,hla-b*39,hla-drb1*07,hla-drb1*11,hla-drb1*13基因攜帶者與非攜帶者間并無差異(p0.05),僅hla-b*58和hla-drb1*09攜帶者與非攜帶者的alb水平明顯不同,前者p=0.015,后者p=0.003,均0.05,但僅有hla-drb1*09在交叉驗證中仍然具有顯著性差異,p=0.017,說明hla-drb1*09不僅是丙肝感染的抵抗基因,還在阻礙alb水平下降及疾病進(jìn)展的過程中起到保護(hù)作用。12、hla-a位點基因頻率(高分辨)與抗體親和力呈正相關(guān),提示基因頻率越高,抗體親和力越強。13、對攜帶hla-a*02,hla-b*39,hla-drb1*09,hla-drb1*11,hla-a*33,hla-b*58,hla-drb1*07,hla-drb1*13基因型別的患者進(jìn)行抗體親和力、抗體物質(zhì)量以及抗體總活性的比較,由于hla-b*39僅有1例陽性患者,hla-drb1*11只有4例陽性患者,故不對此兩種基因型別進(jìn)行比較。結(jié)果顯示,按抗體親和力排序,hla-a*33hla-b*58hla-drb1*07hla-a*02hla-drb1*09hla-drb1*13。14、生物信息學(xué)角度的親和力分析結(jié)果是:hla對hcvns3的親和性排序為:hla-b*58hla-a*33hla-drb1*09hla-drb1*07hla-a*02hla-drb1*13。結(jié)論:1.hcv抗體多維數(shù)據(jù)解析方法成立,hcv感染患者抗體親和力、抗體總活性、抗體物質(zhì)量的變化有可能反應(yīng)肝細(xì)胞損傷及病毒載量的變化,具有一定的臨床應(yīng)用價值。2.hcv抗體多維數(shù)據(jù)解析發(fā)現(xiàn),抗體親和力與病情聯(lián)系密切,優(yōu)于傳統(tǒng)實驗室僅檢測抗體總活性的方法�？贵w親和力在疾病轉(zhuǎn)歸中可能有一定的指示作用,具有較高的診斷效能,高親和力抗體可能有利于疾病的好轉(zhuǎn),測定抗體親和力將有助于臨床醫(yī)生判斷疾病的預(yù)后。3.HLA多態(tài)性與丙型肝炎發(fā)生發(fā)展過程及HCV抗體親和力高低有關(guān),基因頻率高(進(jìn)化保守),可能越有利于產(chǎn)生高親和力的抗體。
[Abstract]:Background: Hepatitis C Virus (HCV) is the main pathogen of post transfusion and sporadic hepatitis and is a worldwide public health problem. Around the world, about 170 million HCV serologically positive patients face the risk of transforming into liver cirrhosis and liver cancer. Although HCV can stimulate the body to produce an effective immune response, but a 80% HCV infection In patients with chronic hepatitis C, only 20% of the patients can effectively remove the virus, recover spontaneously and without any sequelae. Most of the patients with HCV chronic infection can produce antibodies against different HCV virus proteins and detect the presence of these antibodies in the patient's serum. Obviously, the type of host immune response to HCV infection and the type of host immune response are clearly defined. Strength may play an important role in its prognosis for its prognosis,.HCV antibody detection is of great value for the diagnosis of HCV. Neutralizing antibodies can directly act on HCV virus, but it is generally believed that the antibodies commonly detected in HCV infected persons are directed against the HCr43 protein (HCV unstructured region NS3 and core region), c100-3 antigen (HCV non structural NS3, NS4 coding). The antibody, as a non neutralizing antibody, can not determine the immune state of the HCV infected person by detecting the HCV antibody. We found the same non neutralizing antibody in the association of anti-HBc affinity with HBV infection, but the affinity of anti-HBc is closely related to the prognosis of HBV infection; and there are also studies showing that the affinity of antibodies is high and low. It is possible to accurately reflect the activity of cytomegalovirus infection. The determination of HCV antibody affinity may be more accurate to reflect the immune status of HCV infected people and provide valuable information for determining the status and outcome of HCV infection. The total activity of antibodies depends on the content of antibody protein and its binding activity with the anti primitive (affinity). The test of HCV antibody in bed laboratory only detected the total activity of antibody, and did not involve the detection of antibody protein content and antibody affinity. The total activity of HCV antibody was analyzed into antibody protein and antibody affinity, and the detection system of the general activity of HCV antibody was tried to refer to the detection principle of the affinity of hepatitis B anti-HBc. To establish a method to detect the affinity of HCV antibody, and to explore the relationship between the antibody affinity of HCV, the total activity and the quality of the virus, the degree of body damage and the dynamics of the changes in different stages of the disease. The study on the persistence and clearance of HLA and HCV infection in the last ten years is not much, and the immune response of the body to the epitopes of the virus depends on the immune response of the body. Antigen presenting cells are capable of processing and presenting antigen epitopes, and the ability of immune cells to identify these epitopes, which are genetically determined by HLA molecules. Therefore, it is speculated that the HLA type can affect the.Hla-i allele of HCV infection and the self limiting transformation of HCV infection, such as the HLA-I class, etc. The gene A3, B27 and cw*01 are all associated with virus clearance, while B8 is highly compatible to HLA-DR in the.Ns3 region associated with the persistent infection of the virus, suggesting that the hla- class II molecules are also related to the virus clearance. Some hla- class II alleles are also related to the outcome of HCV infection, and the most highly related hla- II class of the virus clearance. The allele is dqb1*0301 gene and drb1*1101., however, the results of these studies are not entirely consistent and even contradictory. Objective: to establish a detection method for affinity of HCV antibodies with antibody multidimensional data analysis, and to explore the changes in the affinity, mass and total activity of HCV antibody, the amount of the virus and the damage process of the body. The relationship between.Hcv and HLA-A, HLA-B, HLA-DRB1 genotypes and the process of disease and its mechanism of action. Methods: 1, the three subcutaneous injection of Recombinant Hepatitis B Vaccine was used to immunize rabbits repeatedly, and the rabbit blood was collected for the first week after the first injection, and the low affinity antibody animal serum was obtained; the third injection was given. After two weeks, rabbit serum was collected to obtain high affinity antibody animal serum, double dilution sera, and double antigen sandwich enzyme-linked immunosorbent assay was used to detect anti-hbs. in 106 cases of HCV infected patients, and HCV antibody was determined by chemiluminescent particle immunization assay, and HCV-RNA was detected by pcr- fluorescence probe. Detection of alt, AST, ALB and other clinical indicators. According to alt, AST level and HCV-RNA level in three groups, the affinity of antibody, the total activity of antibody and the change of the quality of antibody were compared and analyzed, and 328 cases of HCV infected patients were randomly collected, and the HCV antibody and pcr- fluorescence were measured by the chemiluminescent particle immunoassay. HCV-RNA was detected by probe, and alb. was divided into chronic hepatitis group and liver cirrhosis group according to the disease stage. The chronic hepatitis group was divided into ALB normal HCV-RNA negative group (improvement recovery stage) and other group (progressive stage) according to the level of ALB and HCV-RNA, and the changes of antibody affinity, antibody quality and total antibody activity were analyzed and compared. 3, 104 patients with HCV infection and 200 healthy controls were randomly collected. HCV antibody was measured by chemiluminescent particle immunoassay, HCV-RNA was detected by pcr- fluorescence probe, and serum ALB level was detected. The identification of HLA genotypes was carried out by sequencebasedtyping (PCR-SBT). The different HLA types were compared and analyzed. ALB level, antibody affinity, antibody quality and antibody total activity change.4, using online search database combined with discoverystudio (DS) software to analyze and predict the interaction between the 6 kinds of HLA protein fractions of NS3 and hla-drb1*09, hla-a*02, hla-a*33, hla-b*58, hla-drb1*07, hla-drb1*13. The database includes national national medical books Library literature retrieval system NCBI, protein structure database PDB and PROSITE database. Results: 1, the serum antibody affinity of female rabbits after first times immunization is 0.522, second times 0.826 and third times 0.896. The affinity of serum antibody after first immunization of male rabbits is 0.816, second is 0.846 and third is 0.972, which are all gradually increasing and affinity with antibody. The antibody quality of.2, alt, AST normal group was significantly lower than any abnormal group (P0.05), and the antibody affinity was significantly higher than any abnormal group (P0.05). The total antibody activity in the three groups was not significantly different (P0.05).3. According to HCV-RNA level, the normal group of ALT and AST (53 cases) were further divided into two groups. In the group of HCV-RNA negative group and HCV-RNA positive group, the total antibody activity of.Hcv-rna negative group was significantly lower than that of HCV-RNA positive group (P0.05), but the antibody affinity was significantly higher than that of HCV-RNA positive group (P0.05).4, the total antibody activity of the HCV-RNA negative group was significantly lower than the low viral load, and the high virus load group (P0.05), The antibody affinity was significantly higher than the low viral load, high viral load group (P0.05).5, HCV-RNA positive as the dependent variable, antibody affinity, antibody quality and antibody total activity as independent variables, logistic regression analysis, HCV-RNA level with antibody affinity was negatively correlated (P0.05).6, ALB normal HCV-RNA negative group antibody affinity obviously Higher than the other groups of chronic hepatitis and liver cirrhosis (P0.05), the quality of antibody was significantly lower than that of other groups of chronic hepatitis and liver cirrhosis (P0.05). The total antibody activity was not significantly different in the three groups (P0.05).7, and the area of antibody affinity and antibody mass was 0.816,0.811, respectively, which showed high diagnostic efficiency. It was significantly higher than the traditional antibody test (the area under the ROC curve was 0.581). The antibody affinity was 0.873 for the best diagnostic critical point for differentiating the progression of hepatitis C infection (HCV-RNA positive) and the good turn phase (HCV-RNA negative). The higher the antibody affinity, the less the virus replication was.8, and the ratio of the high antibody affinity (> 0.873) in the alb normal HCV-RNA negative group. The cases were significantly higher than the other groups of chronic hepatitis and liver cirrhosis (P0.05).9, the serum of HCV-RNA (+) was neutralized with high affinity antibody, and the lgrna was significantly lower than that before the neutralization level (P0.05).10. In HCV patients and the healthy control group, the 8 HLA types were identified with significant difference (P0.05), hla-a*02, hla-b*39, hla-drb1*09, respectively. Drb1*11, hla-a*33, hla-b*58, hla-drb1*07, hla-drb1*13., hla-a*02, hla-b*39, hla-drb1*09, hla-drb1*11 in HCV patients were significantly lower than those in the healthy control group. Anti gene, while hla-a*33, hla-b*58, hla-drb1*07, and hla-drb1*13 are the sensitive gene.11 of hepatitis C infection. In these 8 HLA types, serum ALB levels are in hla-a*02, hla-a*33, hla-b*39, hla-drb1*07, hla-drb1*11, carriers and non carriers. The level of Alb is obviously different, the former p=0.015 and the latter p=0.003, all 0.05, but only hla-drb1*09 in cross validation still have significant differences, p=0.017, indicating that hla-drb1*09 is not only the resistance gene of hepatitis C infection, but also hinders the decline of ALB and the progression of the disease, which plays a protective role.12, the frequency of the HLA-A site gene (high resolution). There was a positive correlation with antibody affinity, suggesting that the higher the frequency of the gene, the stronger the antibody affinity.13, the antibody affinity, the quality of the antibody and the total activity of the antibody in patients carrying hla-a*02, hla-b*39, hla-drb1*09, hla-drb1*11, hla-a*33, hla-b*58, hla-drb1*07, and hla-drb1*13, because hla-b*39 only had 1 positive patients. Hla-drb1*11 only 4 positive patients did not compare the two genotypes. The results showed that according to the affinity sequencing of antibody, the affinity analysis of hla-a*33hla-b*58hla-drb1*07hla-a*02hla-drb1*09hla-drb1*13.14 and bioinformatics was: the affinity of HLA to hcvns3 was: hla-b*58hla-a*33hla-drb1*09hla-drb1*07hl A-a*02hla-drb1*13. conclusion: the multi-dimensional data analysis method of 1.hcv antibody was established. The antibody affinity, the total activity of the antibody and the change of the quality of the antibody may reflect the changes of the liver cell damage and the viral load. It has certain clinical application value of the.2.hcv antibody multidimensional data analysis, and the affinity of the antibody is closely related to the condition of the disease. It is better than the traditional laboratory to detect the total activity of antibody only. The antibody affinity may have a certain indicator in the outcome of the disease. It has a high diagnostic efficiency. The high affinity antibody may be beneficial to the improvement of the disease. The determination of antibody affinity will help clinicians to judge the prognosis of the.3.HLA polymorphism and the incidence of hepatitis C The development process is related to the high affinity of HCV antibody. The high gene frequency (evolutionary conservatism) may help to produce high affinity antibodies.
【學(xué)位授予單位】：大連醫(yī)科大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2016
【分類號】：R512.63;R446.6

【相似文獻(xiàn)】

相關(guān)期刊論文 前10條

1 楊錫強;;牛奶和大豆制品喂養(yǎng)兒的抗體反應(yīng)[J];國外醫(yī)學(xué)(兒科學(xué)分冊);1983年02期

2 凌育;鳥類抗體的特點及其應(yīng)用前景[J];廣東畜牧獸醫(yī)科技;1995年04期

3 周慶申;預(yù)溫后抗體反應(yīng)減弱或者喪失[J];國外醫(yī)學(xué).輸血及血液學(xué)分冊;2004年01期

4 Kadin SB ,Otternesss IG ,潘啟超;抗體作為藥物的載體與毒性逆轉(zhuǎn)劑[J];國外醫(yī)學(xué).藥學(xué)分冊;1982年01期

5 喬春霞;沈倍奮;;重組多克隆抗體——一類新的治療制劑[J];中國免疫學(xué)雜志;2009年01期

6 黃永安;葛錫銳;;淋巴結(jié)細(xì)胞體外產(chǎn)生抗體的研究[J];實驗生物學(xué)報;1963年03期

7 史英輝;丙型肝炎病毒感染的抗體反應(yīng)與疾病的聯(lián)系[J];預(yù)防醫(yī)學(xué)文獻(xiàn)信息;1996年03期

8 施桂英;周亞非;黃次波;黃烽;虞瑞堯;方彬;劉萬銀;;黑龍江省Lyme病的臨床表現(xiàn)及血清抗體反應(yīng)[J];中國人民解放軍軍醫(yī)進(jìn)修學(xué)院學(xué)報;1991年03期

9 張遠(yuǎn)惠;;鏈球菌抗體與風(fēng)濕熱的早期診斷[J];四川醫(yī)學(xué);1983年02期

10 童貽剛,王海濤;重組完整抗體研究進(jìn)展[J];生物技術(shù)通訊;2001年03期

相關(guān)會議論文 前6條

1 向軍儉;;抗體技術(shù)及其在傳染病研究中的應(yīng)用[A];新發(fā)和再發(fā)傳染病防治熱點研討會論文集[C];2010年

2 向軍儉;;抗體技術(shù)研究和應(yīng)用[A];新發(fā)和再發(fā)傳染病防治熱點研討會論文集[C];2011年

3 孫小林;楊倩;姜穎;周飛;;食蟹猴T細(xì)胞依賴性抗體反應(yīng)實驗中用于檢測KLH抗體濃度的ELISA方法的開發(fā)和驗證[A];2013年（第三屆）中國藥物毒理學(xué)年會暨藥物非臨床安全性評價研究論壇論文摘要[C];2013年

4 孫小林;楊倩;姜穎;周飛;;食蟹猴T細(xì)胞依賴性抗體反應(yīng)實驗中用于檢測KLH抗體濃度的ELISA方法的開發(fā)和驗證[A];中國藥理學(xué)與毒理學(xué)雜志(2013年6月第27卷第3期)[C];2013年

5 任克吉;韓松勇;;氫化可的松琥珀酸鈉在急癥臨床的應(yīng)用[A];第六屆全國危重病學(xué)術(shù)交流大會論文匯編[C];2005年

6 任克吉;韓松勇;;氫化可的松琥珀酸鈉在急癥臨床的應(yīng)用[A];中華醫(yī)學(xué)會急診醫(yī)學(xué)分會全國第11屆創(chuàng)傷復(fù)蘇中毒學(xué)術(shù)會議論文集[C];2005年

相關(guān)重要報紙文章 前6條

1 劉霞;兩種廣譜抗體可強效中和艾滋病病毒[N];科技日報;2009年

2 常麗君;17種新型強效廣譜HIV抗體閃亮登場[N];科技日報;2011年

3 記者 黃磊　周芳;“要知道能成功,還叫什么探索呢”[N];湖北日報;2010年

4 張樂;青壯年易染“非典”探因[N];中國醫(yī)藥報;2003年

5 謝蜀生;一個神秘器官的發(fā)現(xiàn)[N];大眾科技報;2011年

6 陸志城;為AD疫苗研發(fā)帶來新希望[N];醫(yī)藥經(jīng)濟報;2002年

相關(guān)博士學(xué)位論文 前10條

1 王貞;基于抗體多維數(shù)據(jù)的解析探討丙型肝炎病毒抗體親和力在病程中的動力學(xué)變化及與HLA多態(tài)性的關(guān)聯(lián)[D];大連醫(yī)科大學(xué);2016年

2 陳冠杰;聚乙二醇修飾的抗體的理化性質(zhì)及生物學(xué)活性[D];中國協(xié)和醫(yī)科大學(xué);1985年

3 耿樹生;抗CD20抗體的改造及其生物活性研究[D];河北大學(xué);2007年

4 劉銀星;嵌合抗CD20抗體突變體的表達(dá)及其作用機理的研究[D];中國協(xié)和醫(yī)科大學(xué);2003年

5 趙向東;CD34抗體表面修飾去細(xì)胞光氧化牛頸靜脈再內(nèi)皮化的研究[D];中南大學(xué);2008年

6 孟佳子;人源HIV-1廣譜中和Fab抗體的鑒定[D];北京協(xié)和醫(yī)學(xué)院;2013年

7 楊向民;全人抗體高效真核表達(dá)載體的構(gòu)建與表面重塑抗體rCAb1[D];第四軍醫(yī)大學(xué);2008年

8 張春秀;基于抗原/抗體反應(yīng)的生物檢測技術(shù)及其應(yīng)用研究[D];東南大學(xué);2003年

9 于俊巖;抗HBV多聚酶TP區(qū)細(xì)胞內(nèi)VH抗體體外抑制HBV復(fù)制的實驗研究[D];第三軍醫(yī)大學(xué);2006年

10 查昭;抗ErbB2抗體chA21的抗腫瘤活性與作用機理研究[D];中國科學(xué)技術(shù)大學(xué);2013年

相關(guān)碩士學(xué)位論文 前10條

1 谷偉紅;豬CD16及其介導(dǎo)PRRSV抗體依賴性增強作用研究[D];中國農(nóng)業(yè)科學(xué)院;2015年

2 黃世維;檢測鴨源沙門氏菌抗體間接ELISA方法的建立與應(yīng)用[D];四川農(nóng)業(yè)大學(xué);2014年

3 冉葦;人源抗人IgE工程抗體Fab片段的功能研究[D];復(fù)旦大學(xué);2014年

4 張萌;兩種四溴雙酚A類化合物抗體的制備及其生物分析方法的建立[D];江蘇大學(xué);2016年

5 楊啟修;抗抗生素類藥物抗體的檢測與研究和稀有血型分子生物學(xué)篩查[D];華東師范大學(xué);2010年

6 孟凡軍;抗沙門氏菌IgY抗體的制備及其特性分析[D];第四軍醫(yī)大學(xué);2010年

7 張曙儉;勞森氏胞內(nèi)菌的PCR檢測方法及其抗體間接ELISA檢測方法的建立與應(yīng)用[D];南京農(nóng)業(yè)大學(xué);2012年

8 張海譜;抗人糖原磷酸化酶BB抗體的制備臨床應(yīng)用[D];河北醫(yī)科大學(xué);2003年

9 金海燕;重金屬汞多克隆抗體的制備及間接競爭ELISA方法的研究[D];遼寧師范大學(xué);2009年

10 岳園園;人可溶性增殖誘導(dǎo)配體的表達(dá)、純化、活性鑒定以及抗體的制備[D];南京師范大學(xué);2007年

，

本文編號：2050443