The immune system is a critical component in defense against viral, bacterial, parasitic, and fungal diseases. Immunological mechanisms, including immunological mediators, innate immunity, cell-mediated immunity, and humoral-mediated immunity, serve to maintain homeostasis and protect the host from disease. Immunological variation can impact defense mechanisms, however. Two factors in particular that can influence immune function are the single nucleotide polymorphisms (SNPs) and aging. SNPs affecting inflammatory cytokines are an important modifier involved in a number of diseases such as asthma, periodontal disease, atherosclerosis, diabetic retinopathy, psoriasis, and osteoporosis. Age-related alterations to the immune system have also been studied and documented. The genetic makeup of different strains of mice and the age of these different strains cause large differences in susceptibility to infection, with influenza virus infection among the most widely studied. The mechanism of these differences due to either genetics or age is not known but can be investigated in strain- and age-specific infectious disease models.