Host protective antibodies and serum immunoglobulin isotypes in mice chronically infected or repeatedly immunized with the nematode parasite Nematospiroides dubius.

The nematode parasite Nematospiroides dubius survives to give a chronic primary infection in mice. However, mice subjected to weekly infections of 125 larvae, interspersed by treatment with an anthelmintic to prevent the accumulation of lethal numbers of adult worms in the intestine, develop host-protective antibodies in their serum. The protective effect of these antibodies was demonstrated by passive transfer to naive recipients or to mice already adoptively immunized with immune mesenteric lymph node cells (IMLNC). Sera were first shown to exhibit protective activity during the third and fourth weeks of the multiple immunizing infection, reaching a peak level by week six beyond which there was no further increase in protective activity. This increase was correlated with a ten-fold, concurrent rise in serum IgG1 levels. None of the other immunoglobulin isotypes underwent comparable changes in concentration nor could they be correlated with the pattern of appearance of host-protective antibodies in the sera of donor mice. This suggested that host protective antibodies were of the IgG1 class. CFLP and C57BL10 mice (the latter is a weak responder strain) both had high levels of host-protective antibodies in their serum. However when the sera from NIH mice (a strong responder strain) were compared, they exhibited far less protective activity on passive transfer to recipient mice, although when given together with IMLNC, serum from multiply-immunized NIH mice enhanced the protective effect of IMLNC synergistically. When primary infection serum was assayed in this passive/adoptive transfer model, no host-protective antibodies could be demonstrated, even with pools of primary infection serum taken 10 and 17 weeks after infection. These results are discussed with respect to the possible mechanisms by which N. dubius evades the host immune system to give rise to long-lasting primary infections in mice.