Influenza: pathogenesis and host defense.
Our understanding of the host defense and pathogenesis of influenza has come from parallel studies in animal models and humans. Infection is initiated by deposition of influenza particles on either the upper respiratory tract epithelium or directly into the alveoli, with the former method having a lethal dose several orders of magnitude greater than the latter. The virus attaches to its cellular receptor by its hemagglutinin (HA); if this step is blocked by specific antibody, infection does not take place. The major role of antibody is in the prevention of disease. Even though serum antibody (primarily antihemagglutinin, but also antineuraminidase) has been known for decades to prevent viral pneumonia, it has only more recently been shown that passive administration of anti-influenza serum to virgin mice prevents pneumonia, but not rhinotracheitis. Further, intravenously administered anti-influenza IgA has been shown to be specifically transported into the nasal secretions and protect the murine nasopharynx against influenza infection. Whereas antibody is clearly required for protection against influenza, cytotoxic T-lymphocyte (CTL) activity is both necessary and sufficient for recovery from influenza. This was best shown in studies using nude (athymic) mice. Influenza-infected nude mice shed virus from their lungs indefinitely. Adoptive transfer of anti-influenza CTLs to influenza-infected nude mice will clear the virus from their lungs, whereas administration of anti-influenza antibody will lead to a cessation of viral shedding only as long as antibody is present. Influenza in aging presents a serious clinical problem. Recent studies suggest that the age-related decrease in anti-influenza CTL activity causes both prolonged viral shedding and increased viral spread through the respiratory tract.
Bender
B S
BS
Geriatric Research, Education and Clinical Center, Veterans Affairs Medical Center, Gainesville, FL 32608-1197.
Small
P A
PA
D000375:Aging / Q000276:immunology; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D006801:Humans; D007111:Immunity, Cellular; D007071:Immunoglobulin A, Secretory / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007252:Influenza Vaccines / Q000627:therapeutic use; D007251:Influenza, Human / Q000150:complications / Q000276:immunology*; D051379:Mice; D009975:Orthomyxoviridae / Q000472:pathogenicity*
D000914:Antibodies, Viral; D007071:Immunoglobulin A, Secretory; D007074:Immunoglobulin G; D007252:Influenza Vaccines