Influenza A viruses remain a global threat to human health, with continued pandemic potential. In this Review, we discuss our current understanding of the optimal immune responses that drive recovery from influenza virus infection, highlighting the fine balance between protective immune mechanisms and detrimental immunopathology. We describe the contribution of innate and adaptive immune cells, inflammatory modulators and antibodies to influenza virus-specific immunity, inflammation and immunopathology. We highlight recent human influenza virus challenge studies that advance our understanding of susceptibility to influenza and determinants of symptomatic disease. We also describe studies of influenza virus-specific immunity in high-risk groups following infection and vaccination that inform the design of future vaccines to promote optimal antiviral immunity, particularly in vulnerable populations. Finally, we draw on lessons from the COVID-19 pandemic to refocus our attention to the ever-changing, highly mutable influenza A virus, predicted to cause future global pandemics.

甲型流感病毒仍然对人类健康构成全球性威胁，并具有持续大流行的潜力。在这篇综述中，我们讨论了目前对促进流感病毒感染恢复的最佳免疫反应的理解，强调了保护性免疫机制和有害免疫病理学之间的良好平衡。我们描述了先天性和适应性免疫细胞、炎症调节剂和抗体对流感病毒特异性免疫、炎症和免疫病理学的贡献。我们重点介绍最近的人类流感病毒挑战研究，这些研究增进了我们对流感易感性和症状性疾病决定因素的理解。我们还描述了感染和接种疫苗后高危人群中流感病毒特异性免疫的研究，这些研究为未来疫苗的设计提供了信息，以促进最佳的抗病毒免疫力，特别是在弱势群体中。最后，我们吸取 COVID-19 大流行的教训，将我们的注意力重新集中到不断变化、高度变异的甲型流感病毒上，该病毒预计将导致未来的全球大流行。