evidence: In humans, influenza viruses first cause infection by infecting epithelial cells in the respiratory tract. Illness during infection is primarily the result of lung inflammation and compromise caused by epithelial cell infection and death, combined with inflammation caused by the immune system's response to infection. Non-respiratory organs can become involved, but the mechanisms by which influenza is involved in these cases are unknown. Severe respiratory illness can be caused by multiple, non-exclusive mechanisms, including obstruction of the airways, loss of alveolar structure, loss of lung epithelial integrity due to epithelial cell infection and death, and degradation of the extracellular matrix that maintains lung structure. In particular, alveolar cell infection appears to drive severe symptoms since this results in impaired gas exchange and enables viruses to infect endothelial cells, which produce large quantities of pro-inflammatory cytokines.[17] [...] In 1931, Richard Shope published three papers identifying a virus as the cause of swine influenza, a then newly recognized disease among pigs that was characterized during the second wave of the 1918 pandemic.[68][69] Shope's research reinvigorated research on human influenza, and many advances in virology, serology, immunology, experimental animal models, vaccinology, and immunotherapy have since arisen from influenza research.[69] Just two years after influenza viruses were discovered, in 1933, influenza A virus was identified as the agent responsible for human influenza.[68][73] Subtypes of influenza A virus were discovered throughout the 1930s,[69] and influenza B virus was discovered in 1940.[23]