Host antigens in schistosomiasis

It has previously been shown that adult schistosomes excite an immune response in the rhesus monkey but do not themselves succumb to this response. Furthermore, schistosomes are known to persist in the blood of man and experimental animals for long periods. These findings point to the evolution of a special mechanism for circumventing the immune defences of the host. The present paper sets out evidence which suggests that this mechanism involves the incorporation of host antigens at the surface of the adult worm. When adult worms, which had been grown in mice (‘mouse worms’), were transferred into the hepatic portal systems of normal monkeys, a large proportion (84 %) were recovered alive 1 to 6 weeks later. Worms recovered after 1 week were pale and shrunken and the females had ceased egg production; worms recovered after 6 weeks were normal and egg production had been resumed. Evidently, the transferred worms find difficulty at first in adapting to their new host species, but in time they are able to adapt fully. In contrast, when mouse worms were transferred to monkeys previously immunized against normal mouse tissues (anti-mouse monkeys), very few of these worms survived. Indeed, when the monkeys were immunized against mouse spleen and liver cells or erythrocytes, combined with Freund’s complete adjuvant, the transferred mouse worms were completely destroyed. This result indicates that the worms grown in mice had mouse antigens closely associated with them, and that on transfer to anti-mouse monkeys, the worms were destroyed by the ensuing immunological reaction. This immunity was passively transferred to normal monkeys by means of serum; thus the immunity is largely antibody-mediated. Most of the mouse worms died between 7 and 25 h after transfer. The immune reaction was directed mainly against the tegument of the worm, causing breaks in the plasma membrane and vacuolation and subsequent degeneration of the underlying syncytium. The mixed agglutination reaction and the use of a ferritin-labelled antiserum combined with electron microscopy confirmed that host antigens were located at the surface of the worm. The antigens appear to be host species-specific; worms which were grown in monkeys or libyan jirds survived normally when transferred to anti-mouse monkeys. There is evidence that the antigens may readily be exchanged between host and parasites. Mouse worms which were transferred to a normal monkey and then transferred after 7 days to an anti-mouse monkey survived as well as monkey worms. Evidently the mouse worms had lost their mouse antigens during this period, perhaps exchanging them for monkey antigens. Three days in a normal monkey was not sufficient, however, for all of the mouse worms to lose their mouse antigens. It is suggested that these host antigens are synthesized by the host, but that they become firmly bound to or incorporated in the tegument. It is conceivable that these antigens serve to disguise the worms as host tissue, thus preventing their rejection by the immune defences of the host. This hypothesis provides an explanation for the apparent anomalies, referred to earlier: the insusceptibility of adult worms to the immune response which they are known to provoke, and their long persistence in the blood, an immunologically hostile environment.