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泰勒虫病:通过了解对该寄生虫的免疫反应推动疫苗研发进展

Theileriosis: progress towards vaccine development through understanding immune responses to the parasite.

作者信息

Morrison W I, Taracha E L, McKeever D J

机构信息

AFRC Institute for Animal Health, Compton, Near Newbury, UK.

出版信息

Vet Parasitol. 1995 Mar;57(1-3):177-87. doi: 10.1016/0304-4017(94)03119-h.

DOI:10.1016/0304-4017(94)03119-h
PMID:7597782
Abstract

Studies of the immune responses of cattle to Theileria parva have provided evidence that immunity to the parasite can operate at two levels, namely the sporozoite and the schizont-infected lymphoblast. Antibodies that neutralize the infectivity of sporozoites have been detected in the serum of hyperimmunized cattle, and a recombinant sporozoite surface antigen has been shown to induce neutralizing antibodies and protection against experimental challenge. However, the immunity that develops following primary infection with T. parva is accompanied by only low levels of antibodies to sporozoites; there is overwhelming evidence that under these circumstances protection is mediated by T cell responses against infected lymphoblasts. Potent class I MHC-restricted cytotoxic T lymphocyte (CTL) responses are detected in animals recovering from infection and treatment or challenge infections. Two recent findings have provided direct evidence for the importance of these responses in immunity. First, the strain specificity of CTL in cattle immunized with one stock of the parasite was found to correlate with the subsequent susceptibility of individual animals to challenge with a heterologous cloned parasite population (in these circumstances some animals are protected whereas others are susceptible to the heterologous challenge). Second, the adoptive transfer of lymphocytes highly enriched for CD8+ T cells, from immune to naive identical twin calves, was found to protect against experimental challenge. The CTL response in individual animals appears to be directed towards a limited number of antigenic epitopes. The antigenic specificity is determined in part by class I MHC phenotype although there is evidence that other phenomena such as antigenic competition are also involved. Current efforts are directed towards identification of the parasite antigens recognized by CTL with the eventual aim of exploring their potential for vaccination.

摘要

对牛对泰勒虫免疫反应的研究表明,对该寄生虫的免疫可在两个层面发挥作用,即子孢子和裂殖体感染的淋巴母细胞层面。在超免疫牛的血清中已检测到中和子孢子感染性的抗体,并且一种重组子孢子表面抗原已被证明可诱导中和抗体并提供针对实验性攻击的保护。然而,初次感染泰勒虫后产生的免疫仅伴随着低水平的子孢子抗体;有大量证据表明,在这些情况下,保护是由针对感染淋巴母细胞的T细胞反应介导的。在从感染、治疗或攻击感染中恢复的动物中检测到了强大的I类主要组织相容性复合体(MHC)限制性细胞毒性T淋巴细胞(CTL)反应。最近的两项发现为这些反应在免疫中的重要性提供了直接证据。首先,在用一种寄生虫株免疫的牛中,CTL的株特异性与个体动物随后对异源克隆寄生虫群体攻击的易感性相关(在这些情况下,一些动物受到保护,而另一些动物易受异源攻击)。其次,发现从免疫的同卵双生子犊牛向未免疫的同卵双生子犊牛过继转移高度富集CD8 + T细胞的淋巴细胞可提供针对实验性攻击的保护。个体动物中的CTL反应似乎针对有限数量的抗原表位。抗原特异性部分由I类MHC表型决定,尽管有证据表明其他现象如抗原竞争也参与其中。目前的努力旨在鉴定CTL识别的寄生虫抗原,最终目的是探索它们在疫苗接种方面的潜力。

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Theileriosis: progress towards vaccine development through understanding immune responses to the parasite.泰勒虫病:通过了解对该寄生虫的免疫反应推动疫苗研发进展
Vet Parasitol. 1995 Mar;57(1-3):177-87. doi: 10.1016/0304-4017(94)03119-h.
2
Parasite strain specificity of precursor cytotoxic T cells in individual animals correlates with cross-protection in cattle challenged with Theileria parva.个体动物中前体细胞毒性T细胞的寄生虫株特异性与感染泰勒虫的牛的交叉保护相关。
Infect Immun. 1995 Apr;63(4):1258-62. doi: 10.1128/iai.63.4.1258-1262.1995.
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Orientation of bovine CTL responses towards PIM, an antibody-inducing surface molecule of Theileria parva, by DNA subunit immunization.通过DNA亚单位免疫使牛细胞毒性T淋巴细胞(CTL)反应定向于PIM,即泰勒虫的一种抗体诱导表面分子。
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Theileria parva candidate vaccine antigens recognized by immune bovine cytotoxic T lymphocytes.被免疫牛细胞毒性T淋巴细胞识别的泰勒虫候选疫苗抗原。
Proc Natl Acad Sci U S A. 2006 Feb 28;103(9):3286-91. doi: 10.1073/pnas.0511273103. Epub 2006 Feb 21.
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Immunization with one Theileria parva strain results in similar level of CTL strain-specificity and protection compared to immunization with the three-component Muguga cocktail in MHC-matched animals.在 MHC 匹配的动物中,与用三分量穆古加鸡尾酒疫苗免疫相比,用一种泰勒虫小种菌株免疫可产生相似水平的细胞毒性 T 淋巴细胞菌株特异性和保护作用。
BMC Vet Res. 2018 May 2;14(1):145. doi: 10.1186/s12917-018-1460-x.
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Adoptive transfer of immunity to Theileria parva in the CD8+ fraction of responding efferent lymph.将对小泰勒虫的免疫通过应答性输出淋巴的CD8⁺组分进行过继转移。
Proc Natl Acad Sci U S A. 1994 Mar 1;91(5):1959-63. doi: 10.1073/pnas.91.5.1959.
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The biological and practical significance of antigenic variability in protective T cell responses against Theileria parva.针对小泰勒虫的保护性T细胞应答中抗原变异性的生物学及实际意义。
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Parasite strain specificity of bovine cytotoxic T cell responses to Theileria parva is determined primarily by immunodominance.牛细胞毒性T细胞对小泰勒虫反应的寄生虫株特异性主要由免疫显性决定。
J Immunol. 1995 Nov 15;155(10):4854-60.
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Immunity and vaccine development in the bovine theilerioses.牛泰勒虫病的免疫与疫苗研发
Adv Parasitol. 1999;44:41-97. doi: 10.1016/s0065-308x(08)60230-4.
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Vaccines against Theileria parva.
Ann N Y Acad Sci. 2000;916:464-73. doi: 10.1111/j.1749-6632.2000.tb05326.x.

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Immunology. 2003 Oct;110(2):234-41. doi: 10.1046/j.1365-2567.2003.01731.x.
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Linear peptide specificity of bovine antibody responses to p67 of Theileria parva and sequence diversity of sporozoite-neutralizing epitopes: implications for a vaccine.牛对泰勒虫p67的抗体反应的线性肽特异性及子孢子中和表位的序列多样性:对疫苗的意义
Infect Immun. 1999 Mar;67(3):1261-6. doi: 10.1128/IAI.67.3.1261-1266.1999.