We have used an ex vivo influenza challenge model in human peripheral blood mononuclear cells (PBMC) to simulate the cell-mediated immune response to natural infection and have shown that the level of GrB activity in lysates of A/H3N2 challenged PBMC correlates with protection against laboratory-confirmed influenza A/H3N2 infection (LCII) in older adults (McElhaney et al., 2006; McElhaney et al., 2009; Shahid et al., 2010). Here, GZMB is linked to influenza.