Protective immunity to Nippostrongylus brasiliensis: the sequence of events which expels worms from the rat intestine.

Abstract

In these experiments, adult Nippostrongylus brasiliensis worms were damaged by protective antibodies in either actively or passively immunized rats. These damaged worms were then transplanted into the intestines of normal recipient rats, from which they were rapidly expelled. The rapid expulsion of damaged worms from normal recipients was an active process because when recipients were irradiated, the damaged worms were not expelled. Furthermore, when irradiated recipients were given protective antibodies as well as damaged worms they were still unable to expel the damaged worms. The active expulsion mechanism present in normal rats seems unlikely to be a specific immunological event because treatment of recipients with anti-lymphocytic serum (ALS) did not mimic the effect of irradiation. That is, ALS treatment did not prevent the expulsion of the damaged worms although it suppressed the induction of active immunity. These experiments show that, when immunity acts to expel adult worms from the rat small intestine, two separate and sequential steps which do not require complement are involved: (1) The initial and essential first step is the action of protective antibodies on the worms. In this process the worms are damaged; changes occur in some enzymes and the structure of their gut cells deteriorates. Once these antibody-induced changes have occurred, they are irreversible and the damaged worms are susceptible to the second step. (2) The second step expels the worms. It acts completely independently of the presence of protective antibodies but cannot act unless step (1) has already occurred. The factors involved are present in normal rats. In this report, no evidence of the nature of this step is presented except that it is prevented by irradiation and slightly affected by ALS treatment. If the release of pharmacologically active amines from mast cells is important in immunity, as suggested by other workers, it would be involved in this step. This work refutes the `leak lesion' hypothesis for worm expulsion. The `leak lesion' hypothesis proposed that, in order for protective antibodies to affect the worms, the intestinal mucosa had first to be damaged by a local anaphylactic reaction and that worm expulsion was the direct consequence of the action of protective antibodies on the worms. It is now clear that the action of protective antibodies alone cannot cause the worms to be expelled and that, if anaphylaxis is involved, its action is subsequent to the antibody-mediated damage to the worms.