Three years after the pandemic, major advances have been made in our understanding of the innate and adaptive immune responses to the influenza A(H1N1)pdm09 virus and those responses' contribution to the immunopathology associated with this
infection. Severe disease is characterized by early secretion of proinflammatory and immunomodulatory
cytokines. This
cytokine secretion persisted in patients with severe
viral pneumonia and was directly associated with the degree of viral replication in the respiratory tract.
Cytokines play important roles in the
antiviral defense, but persistent
hypercytokinemia may cause inflammatory tissue damage and participate in the genesis of the
respiratory failure observed in these patients. An absence of pre-existing protective
antibodies was the rule for both mild and severe cases. A role for pathogenic immunocomplexes has been proposed for this disease. Defective T cell responses characterize severe cases of
infection caused by the influenza A(H1N1)pdm09 virus. Immune alterations associated with accompanying conditions such as
obesity, pregnancy or
chronic obstructive pulmonary disease may interfere with the normal development of the specific response to the virus. The role of host immunogenetic factors associated with disease severity is also discussed in this review. In conclusion, currently available information suggests a complex immunological dysfunction/alteration that characterizes the severe cases of 2009 pandemic
influenza. The potential benefits of prophylactic/therapeutic interventions aimed at preventing/correcting such dysfunction warrant investigation.