Hackett Charles J
Division of Allergy, Immunology, and Transplantation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-6601, USA.
J Allergy Clin Immunol. 2003 Oct;112(4):686-94. doi: 10.1016/s0091-6749(03)02025-6.
Biodefense strategies require protection against a broad and largely unforeseen spectrum of pathogens--the forte of innate immune system defenses--that have evolved over millennia to function within moments of encountering either ancient or newly emerging pathogens. Although constitutive, the innate immune system is activated by the presence of microbes or their products, providing a rationale for a potential biodefense strategy. Both prophylactic and postexposure strategies involving innate immune stimulation have been shown to be plausible to prevent or ameliorate infections in animal models. Innate immune-activating compounds based on conserved microbial components recognized by toll-like molecules and other receptors could be synthesized and delivered like drugs by using an entirely different strategy from conventional vaccination. However, important theoretic and practical questions emerge about developing and deploying innate immune protective strategies for biodefense. This rostrum discusses prospects and problems in the overall approach itself. Important topics include microbe-specific issues about innate immune system effectiveness against highly virulent pathogens and general questions, such as whether innate immune responses will be safe and effective if used in a diverse human population of different age groups and with different genetic makeups.
生物防御策略需要针对广泛且在很大程度上无法预见的病原体谱提供保护，这正是固有免疫系统防御的长处所在。这些病原体历经数千年进化，在接触古老或新出现的病原体后数分钟内即可发挥作用。尽管固有免疫系统是组成性的，但微生物或其产物的存在可激活该系统，这为潜在的生物防御策略提供了理论依据。在动物模型中，涉及固有免疫刺激的预防和暴露后策略均已证明对预防或减轻感染具有可行性。基于Toll样分子和其他受体识别的保守微生物成分的固有免疫激活化合物可以合成，并像药物一样通过与传统疫苗完全不同的策略进行递送。然而，在开发和部署用于生物防御的固有免疫保护策略方面，出现了重要的理论和实际问题。本次专题讨论将探讨整体方法本身的前景和问题。重要主题包括关于固有免疫系统针对高毒力病原体有效性的微生物特异性问题，以及一些一般性问题，例如如果在不同年龄组和不同基因构成的多样化人群中使用，固有免疫反应是否会安全有效。
