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暴露于眼镜蛇毒液和纯化毒素组分后家兔细胞免疫反应的评估。

Evaluation of cellular immune response in rabbits after exposure to cobra venom and purified toxin fraction.

作者信息

Suntrarachun Sunutcha, Laoungbua Panithi, Khunsap Suchitra, Noiporm Jureeporn, Suttisee Rattana

机构信息

Research and Development, Queen Saovabha Memorial Institute, Thai Red Cross Society, Bangkok, Thailand.

Snake Farm, Queen Saovabha Memorial Institute, Thai Red Cross Society, Bangkok, Thailand.

出版信息

Environ Anal Health Toxicol. 2024 Dec;39(4):e2024029-0. doi: 10.5620/eaht.2024029. Epub 2024 Dec 24.

DOI:10.5620/eaht.2024029
PMID:39973075
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11852295/
Abstract

Snakebite by a cobra is considered neurotoxic as the cause of neuromuscular paralysis mediated by low molecular weight toxins, which are major toxin components of cobra. However, these toxins represent a problem in generating antibodies owing to their low immunogenicity. Developing complementary strategies to improve the antibody response could be a useful approach to creating better therapeutic antivenoms with higher neutralizing potencies. To develop simple immunization strategies for more potent antivenoms by studying the effects of combining crude cobra venom and toxin fraction in a complementary way. The evaluation of specific cell immunology and cytokine mediators for relevant immune responses will be measured in a rabbit model using four simple immunization strategies. Flow cytometry will be used to quantify the number of B and T cells, and qRT-PCR will be used to ascertain the cytokine genes expressed. B cells with anti-CD20 were seen on D14, and a booster dose was insufficient to maximize the antibodies. Conversely, anti-CD5 for T cells decreased periodically but remained stable. Using a mixture of crude cobra venom and its <10 kDa fraction, peak expression of pro-inflammatory cytokine genes was seen in D42 or D58, with a rise of 4 and 6 folds. Similarly, gene expression of pro-inflammatory cytokines was greater than that of anti-inflammatory cytokines (IL-4 and IL-10), which were up-regulated after D42. Thus, immunization with both the crude and its <10 kDa fraction of cobra venom seems to have synergistic effects that boost cytokines, activate the immune system, and cause lymphocyte differentiation.

摘要

眼镜蛇咬伤被认为具有神经毒性,是由低分子量毒素介导的神经肌肉麻痹的原因,这些毒素是眼镜蛇的主要毒素成分。然而,由于这些毒素的免疫原性低,在产生抗体方面存在问题。开发互补策略以改善抗体反应可能是创造具有更高中和效力的更好治疗性抗蛇毒血清的有用方法。通过以互补方式研究粗眼镜蛇毒和毒素组分组合的效果,开发更有效的抗蛇毒血清的简单免疫策略。将使用四种简单免疫策略在兔模型中测量相关免疫反应的特异性细胞免疫学和细胞因子介质的评估。流式细胞术将用于量化B细胞和T细胞的数量,qRT-PCR将用于确定表达的细胞因子基因。在第14天观察到带有抗CD20的B细胞,一次加强剂量不足以使抗体最大化。相反,T细胞的抗CD5周期性下降但保持稳定。使用粗眼镜蛇毒及其<10 kDa组分的混合物,在第42天或第58天观察到促炎细胞因子基因的峰值表达,增加了4倍和6倍。同样,促炎细胞因子的基因表达大于抗炎细胞因子(IL-4和IL-10),它们在第42天后上调。因此,用粗眼镜蛇毒及其<10 kDa组分进行免疫似乎具有协同作用,可促进细胞因子、激活免疫系统并导致淋巴细胞分化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6076/11852295/9c889692af87/eaht-39-4-e2024029f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6076/11852295/5a7caab72bec/eaht-39-4-e2024029f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6076/11852295/cd7f164bfe60/eaht-39-4-e2024029f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6076/11852295/8bbc0128faab/eaht-39-4-e2024029f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6076/11852295/9c889692af87/eaht-39-4-e2024029f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6076/11852295/5a7caab72bec/eaht-39-4-e2024029f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6076/11852295/cd7f164bfe60/eaht-39-4-e2024029f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6076/11852295/8bbc0128faab/eaht-39-4-e2024029f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6076/11852295/9c889692af87/eaht-39-4-e2024029f4.jpg

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本文引用的文献

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B and T lymphocytes in rabbits change according to the sex and throughout the year.
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