Defense Mechanisms Against Primary Influenza Virus Infection in Mice

Abstract

To investigate the defensive roles and production of interferon and antibodies, C3H/He mice were subjected to various immunosuppressive treatments and infected with influenza virus. In infected normal control mice the pattern of pulmonary viral growth can be divided into three phases. The first phase is characterized by an exponential increase of virus titer, the second by a rapid decrease, and the third by a moderate decrease. At the time of transition from the first phase to the second in pulmonary virus growth, interferon could be detected in the tracheobronchial washings of infected mice, but neutralizing antibodies could not. In infected B cell-deprived mice and infected anti-µ-treated mice, the transition from the first phase to the second occurred without any detectable antibody production, and interferon could be induced in the early stage of infection. However, the pulmonary virus in these mice increased again exponentially until the death of the mice. In infected T cell-deprived mice which could not induce interferon, but produced IgM-neutralizing antibodies, the second phase was not observed after the first phase, but a transient plateau phase could be demonstrated, and then the pulmonary virus increased again exponentially until the death of the mice. In anti-γ-treated infected mice, pulmonary virus growth and production of interferon and neutralizing antibody were almost similar to those of infected normal control mice except for the absence of IgG neutralizing antibody production. Although anti-α-treated infected mice produced interferon and no IgA antibody, the transition from the first exponential increase of pulmonary virus to the second rapid decrease was seen, but then the virus increased exponentially again until the death of the mice. These results suggest that interferon plays an important role in the transition from the first phase to the second, and that T cells are required for interferon induction in mice infected with influenza virus. These data also suggest that IgA antibodies play an important role in the inhibition of virus propagation in the lungs after the disappearance of interferon. Moreover, infected T cell-deprived mice could produce only IgM neutralizing antibodies, but not IgG and IgA antibodies. Therefore, T cells are required for the production of IgG and IgA antibodies and eventually for defense functions in mice infected primarily with influenza virus.

Using Mathematical Model to Depict the Immune Response to Hepatitis B Virus Infection

“…The cellular response can also be sufficient to clear the HBV infection from an individual (Asquith et al, 2003). In the absence of adaptive immunity, the viral load is brought down to very low levels, although not completely cleared, which is supported by experiments showing that in some circumstances antibody response is necessary to clear the infection (Iwasaki et al, 1977). For example, in nude mice without antibodies the viral particles survive with chronic infection (Scherle et al, 1992).…”

“…For example, in nude mice without antibodies the viral particles survive with chronic infection (Scherle et al, 1992). After transferring T helper cells into the infected mice that promotes antibody response, the disease is completely cleared (Iwasaki et al, 1977;Scherle et al, 1992). Therefore, one can conclude that innate defense mechanisms are not capable of curing the disease on their own in the absence of antibody response, and can only reduce the disease to a chronic state.…”

“…Damage increases if either ψ or β is decreased. Very low values of ψ or β result in excessive damage (over 50%) which may presumably lead to secondary infections or death (Iwasaki et al, 1977). When the interferon production rate constant is two times bigger than the baseline value (i.e., when ψ=5,000), then the host remains contagious for about 3-5 days.…”

Defense Mechanisms against Influenza Virus Infection in the Respiratory Tract Mucosa

“…This implies that immune CD4 + T cells in these chimeras function to help the Ig-producing B cells. The recovery process involves two phases: an early phase (days 5 -7), characterized by a rapid decrease in virus titer, is T-cell-dependent, while a late phase (day 7 onwards), characterized by a more protracted decrease that ultimately results in clearance, is B-cell-dependent (87,88). These results suggest that influenza viruses after primary infection are eliminated initially via killing of the virusinfected epithelial cells by MHC class I-restricted CD8 + CTLs, which appear transiently in the respiratory mucosa with a peak on day 7 postinfection.…”