Humoral Immunity

As noted above, antibodies play a role in clearing HSV infections in a direct manner by viral neutralization and by acting in concert with other cells (e.g., NK cells) to reduce the viral load. As a result of these activities, antibodies have the potential to significantly reduce the extent of viral spread and pathogenesis. To date, most of the studies that have examined the influence of psychological stress on the B cells during an HSV infection have focused on measuring antibody titers. For example, as compared with individually housed mice, group-housed mice were shown to produce lower levels of some, but not all, cytokines in response to HSV-1 infection; the kinetics of this response was not altered. However, these group housing conditions were shown not to alter levels of circulating IgM or IgG antibody. Therefore, these stress-induced changes in cytokine production did not translate into altered circulating IgM or IgG antibody titers (Karp et al., 1997). In contrast, another study showed that footshock stress altered cytokine production and increased circulating anti-HSV IgM titers in response to a subcutaneous HSV challenge (Brenner and Moynihan, 1997). These footshock stress-induced increases in antibody titers were found in both BALB/c and C57BL/6 mice. In contrast, another study showed that footshock stress administered at the time of HSV-1 challenge via footpad scarification reduced IgM titers (Kusnecov et al., 1992). The differences in the results obtained between these studies may be primarily due to differences in shock intensity, suggesting that the more stressful the event, the more likely that immunosuppression is to occur. The observed relationship between stress and anti-HSV antibodies in murine models has also been extended to studies in humans. For example, Glaser and Kiecolt-Glaser (1997) demonstrated that caregivers of individuals suffering from dementia had increased antibody titers to whole viral antigen but exhibited no difference in neutralizing antibody titers to a latent HSV-1 infection.

The ability of an individual to generate HSV-specific antibodies after a primary infection may be important, to a limited extent, in protecting the host against reinfection either as a consequence of peripheral reexposure to HSV or from reactivation of the latent virus. Although a less common route of transmission, the acquisition of HSV by a neonate, most often from their mother during delivery, is still a significant health concern and results in a number of Cesarean sections annually. In the case of neonatal HSV infections, the transfer of HSV-specific antibody from mother to child is extremely important in protecting the health of the newborn infant. Thus, any change in this transfer via either the placental (prenatal transfer) or transmammary (postnatal transfer) routes could compromise the resistance of the newborn to herpetic infection. Using a murine model, recent studies from our laboratory provided evidence that a previous HSV-2 infection in female mice protects their offspring against HSV-2 infection (Yorty and Bonneau, 2003,2004a) and that this protection is associated with the transfer of high titers of HSV-specific antibodies. Furthermore, these studies demonstrated that an acute stressor does not affect either trans-mammary (Yorty and Bonneau 2004b) or placental transfer of anti-HSV antibodies to newborn mice despite high circulating levels of corticosterone (Yorty and Bonneau, 2004a). In contrast, sustained elevated levels of corticosterone in the mother immediately after parturition diminishes the serum and milk levels of HSV-2 antibodies and thus reduces the amount of antibody available to the neonates. This corticosterone-mediated reduction in antibody transfer is accompanied by increased HSV-2 susceptibility in neonatal mice who were nursed by these mothers (Yorty et al., 2004).

The above findings demonstrate that how stress modulates the immune response depends on a variety of factors, including the type of stressor as well as the stage of infection (e.g., primary or latent). Furthermore, these studies demonstrate that stress can affect both the active generation as well as the passive transfer of antibodies.

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