Though complement has been traditionally regarded as playing an important role in protection from bacterial infections, it also plays a significant role in the innate response to a number of viruses including VSV, mumps, measles, Newcastle disease, parainfluenza viruses, and influenza virus. The C9 cascade has unique and essential roles in early responses to infection such as direct virus neutralization, induction of chemotaxis, enhancement of phagocytosis,Aciclovir immune complex clearance, and lysis of infected cells. While natural antibodies play an important role in eliciting an effective immune response against primary infections with influenza virus, natural IgM does not effectively neutralize influenza virus in the absence of C9. This also holds true for other types of low affinity Abs, such as cross-reactive Abs. Further, it has been shown that C9 can fix Ab to mediate opsonization or membrane attack, via the classical pathway. From a clinical context, seasonal influenza epidemics are comprised of disease among individuals previously infected with closely related strains in prior seasons; this indicates that cross-reactive Abs are often not adequate to protect healthy adults, even in the presence of normal C9. In fact, the role that cross-reactive Ab plays in protecting a patient from a new influenza virus infection is highly strain-dependent. We hypothesize that differences in C9 between Teniposide pregnant women and other healthy adult populations contribute to the increased disease severity seen in the pregnant population. Here we developed a model that enabled us to identify the unique and non-redundant roles of C9 in influenza virus neutralization with influenza-naı ¨ve serum. While C9 effects indirectly enhance the downstream immune response, we have more recently come to appreciate that the C9 system can also directly regulate humoral immunity and T cell functions. Therefore, alterations in C9 levels and/or function have the potential for broader effects on the whole immune response to a pathogen. The role of C9 in increased severity of influenza during pregnancy, however, has not been previously explored. C9 activation is correlated with poor pregnancy outcomes such as pre-eclampsia and preterm birth, leading to the proposal that C9 inhibition is an ‘‘absolute requirement’’ of normal pregnancy.