Abstract:
Regardless of microbial virulence (i.e., the global infection-fatality ratio), age generally drives the prevalence of death from infection in unvaccinated humans. Four mortality patterns are recognized: the common U- and L-shaped curves of endemic infections and the unique W- and J-shaped curves of pandemic infections. We suggest that these patterns result from different sets of human genetic and immunological determinants. In this model, it is the interplay between (1) monogenic genotypes affecting immunity to primary infection that preferentially manifest early in life and related genotypes or their phenocopies, including auto-antibodies, which manifest later in life and (2) the occurrence and persistence of adaptive, acquired immunity to primary or cross-reactive infections, which shapes the age-dependent pattern of human deaths from infection.
摘要:
无论微生物毒力如何(即,全球感染-死亡率),年龄通常会导致未接种疫苗的人感染死亡的患病率。认识到四种死亡模式:地方性感染的常见U形和L形曲线以及大流行感染的独特W形和J形曲线。我们建议这些模式是由不同的人类遗传和免疫学决定因素引起的。在这个模型中,这是之间的相互作用(1)影响免疫原发感染的单基因基因型,优先表现在生命早期和相关基因型或其表型,包括自身抗体,这体现在以后的生活中,以及(2)适应性的发生和持续,对原发性或交叉反应性感染的获得性免疫,这塑造了人类感染死亡的年龄依赖性模式。