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首页> 外文期刊>Immunology and Cell Biology >Skin delivery of a hybrid liposome/ISCOM vaccine implicates a role for adjuvants in rapid modulation of inflammatory cells involved in innate immunity before the enhancement of adaptive immune responses.
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Skin delivery of a hybrid liposome/ISCOM vaccine implicates a role for adjuvants in rapid modulation of inflammatory cells involved in innate immunity before the enhancement of adaptive immune responses.

机译：混合脂质体/ ISCOM疫苗的皮肤输送牵涉佐剂在增强适应性免疫应答之前快速调节先天免疫所涉及的炎症细胞。

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There is now compelling evidence that intradermal vaccination with an efficacious adjuvanted antigen triggers a series of coordinated responses characterized initially by the rapid mobilization and recruitment of granulocytes to the lung. Activation of effector cells of the innate immune system is intended to provide surveillance and temporary protective cover at vulnerable mucosal sites while both T and B cell precursors, as well as haematopoietic progenitor cells, are undergoing dramatic reductions in numbers during the first 2-4 days post-vaccination. Some of these events recapitulate those seen after infection with a pathogen. Initial decreases in cell numbers in the thymus and bone marrow (BM) are followed by rapid increases in cellular proliferation in these organs, probably in response to peripheral signals. Vaccine-induced cell death (by apoptosis) in the thymus may provide one of many stimuli needed to up-regulate BM production of progenitor cells, and cells of the B, myeloid and monocytic lineages so that depleted peripheral compartments are replenished. Reconstitution of the latter cell population is critical in ensuring sufficient numbers of APC are generated to deal with extraneous antigen resulting from either vaccination or proliferation of a pathogen. Ultimately, these APC, as effector cells of the innate immune system, must provide pattern recognition of dangerous pathogens and serve to activate appropriate T cell responses. Vaccination not only educates both the innate and adaptive arms of the immune response but also more interestingly, appears to regulate subsequent innate immune responses following exposure to a lethal challenge dose of bacteria. Under these conditions, the rate of loss of BM precursors is greatly attenuated in mice previously vaccinated with adjuvanted antigen compared to unvaccinated controls or mice that had received only antigen. Mice intradermally vaccinated with adjuvanted antigen also displayed increased rates of granulocyte and monocyte recruitment in the lung and spleen. These events occurred very rapidly within 12-36 h of challenge and may be crucial in providing complete protection in vaccinated mice against a challenge dose that was otherwise lethal for unvaccinated controls. Therefore, an important characteristic of an efficacious intradermal vaccine may be the ability to deplete T and B precursors in the thymus and BM lymphoid compartments followed by increased rates of haematopoiesis to re-supply peripheral requirements for granulocytes/monocytes, and T and B cells. Adaptive immunity elicited by intradermal vaccination is, therefore, dependent upon prior activation of the innate immune system.
机译：现在有令人信服的证据表明，用有效的佐剂抗原进行皮内接种可引发一系列协同反应，其特征是粒细胞迅速动员并募集到肺中。先天免疫系统效应细胞的激活旨在在易受感染的粘膜部位提供监视和临时保护覆盖，而T和B细胞前体以及造血祖细胞在最初2-4天中的数量正急剧减少。接种后。其中一些事件概括了感染病原体后看到的事件。胸腺和骨髓（BM）中细胞数量最初减少，随后这些器官中细胞增殖迅速增加，这可能是由于对周围信号的响应。胸腺中疫苗诱导的细胞死亡（通过凋亡）可能是上调祖细胞BM生成所需的许多刺激之一，B细胞，髓样细胞和单核细胞谱系的细胞也因此被耗尽。后一种细胞群体的重建对于确保产生足够数量的APC来处理因病原体的疫苗接种或增殖而产生的外源抗原至关重要。最终，这些APC作为先天免疫系统的效应细胞，必须提供危险病原体的模式识别并起激活适当T细胞反应的作用。疫苗接种不仅可以教育免疫反应的先天和适应能力，而且更有趣的是，在暴露于致死性攻击剂量的细菌后，似乎可以调节随后的先天免疫反应。在这些条件下，与未接种疫苗的对照组或仅接受抗原的小鼠相比，先前接种过佐剂抗原的小鼠中BM前体的丢失率大大降低。皮内接种佐剂抗原的小鼠在肺和脾脏中的粒细胞和单核细胞募集率也增加。这些事件在攻击后12-36 h内迅速发生，对于在接种疫苗的小鼠中提供完全保护以免受到未接种对照致死的攻击剂量可能至关重要。因此，有效的皮内疫苗的重要特征可能是耗尽胸腺和BM淋巴区室中的T和B前体的能力，然后增加造血速率以重新供应粒细胞/单核细胞以及T和B细胞的外围需求。因此，皮内接种疫苗引起的适应性免疫取决于先天免疫系统的激活。

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