Based on results from studies using specimens from subjects immunized with attenuated typhoid vaccines, we surmise that serum antibodies, SIgA, CD4+, CD8+, and other T-cell subsets (e.g., mucosal associated invariant T-cells, MAIT), as well as the interaction between T, B, and antigen-presenting cells (APC, e.g., macrophages, DC) are all likely to contribute to an effective acquired immune response against typhoid fever (Figure 1). The gene discussed is CD8A; the disease is typhoid fever.