The role of cell-mediated immunity in ameliorating infection caused by novel influenza strains has been the focus of intense study [48] and it is, therefore, the most compelling area to investigate in order to identify immunogenetic factors that predict severity of pandemic H1N1 influenza. A comprehensive investigation was undertaken by Bermejo-Martin et al. [49] in a study from Spain. They enrolled 19 critically ill patients with primary pH1N1 influenza pneumonia and used gene expression analysis in order to identify host immune responses associated with severe disease defined by illness requiring mechanical ventilation. They identified impaired expression of a number of MHC class II and MHC class I genes, T-cell receptor-associated genes, and also of a cluster of genes thought to be involved in dendritic cell maturation, indicating defective antigen presentation in the most severe group of patients. They found further evidence for the effect of altered antigen presentation on the development of an appropriate adaptive response against the virus in the impaired expression of a group of genes critical to the activation and function of both T and B cells. The group with severe illness also showed higher expression of genes involved in IL-6 and IL-10 pathways, and these results were in concordance with the high serum levels of IL-6 and IL-10 in the group dependant on mechanical ventilation. The authors concluded that severe disease is associated with an impaired transition from innate to adaptive immunity in response to the pH1N1 virus, similar to observations in the context of SARS and severe infections caused by H5N1. The impaired adaptive response was also associated with delayed viral clearance. This study did not, however, explore the role of genetic polymorphisms in this immune dysregulation.