The systemic and mucosal immune response of humans to influenza A virus.

Abstract

Influenza A virus contains a negative-sense, single-stranded RNA genome which consists of 8 segments that code for 7 structural and 3 non-structural proteins (Murphy et al. 1985). In nature, the virus undergoes antigenic changes, referred to as antigenic drift and shift, that permit it to escape from immunity induced by prior infection with related influenza A viruses (Murphy et al. 1985). Common to both types of antigenic change are alterations in the surface glycoproteins, hemagglutinin (HA) and neuraminidase (NA) (Murphy et al. 1985). Antibodies to the HA glycoprotein neutralize the infectivity of the virus, and antibodies to the NA prevent efficient release of virus from infected cells (Askonas et al. 1982; Becht et al. 1971). Passive transfer of monoclonal antibodies to the HA or NA glycoprotein protects mice from experimental challenge with wild type influenza virus whereas those to the membrane (M) protein or nucleoprotein (NP) fail to protect (Askonas et al. 1982). Clearly, the surface glycoproteins constitute the major protective antigens against which an immune response is directed. Immunization of animals with purified NP or with NP expressed by a vaccinia virus induces partial resistance to lethal wild type virus challenge, but the level of resistance is considerably less than that induced by immunization with HA (Andrew et al. 1986; Wraith et al. 1986). It is thought that the resistance induced by immunization with NP is mediated primarily by histocompatibility class I restricted cytotoxic T-cells, but is not limited to this T-cell subset (McDermott et al. 1987; Taylor et al. 1986).