Immunity to tapeworms : vaccination against Hymenolepis diminuta and role of the bursa of Fabricius in rejection of Raillietina cesticillus
Attempts were made to vaccinate mice against infection with Hymenolepis diminuta, a tapeworm rejected from the se hosts by an immunologically- mediated mechanism. Various putative antigenic preparations from the strobilated worm were tested. Marginal protection, as compared with that induced by an oral infection from cysticercoids, was obtained when mice were orally vaccinated with multiple doses of whole worm antigens. Marginal protection was also obtained when tegument antigens were given by this route. Results from two other experiments with tegument antigens, however, did not confirm this finding. No protection was obtained following vaccination with antigens ,from sonic disruption of somatic cells, exoantigens, saline extracts or egg antigens. On the basis of evidence from other experimental models, it is proposed that this failure to evoke strong protective immunity by vaccination with killed worm antigens was possibly due to one or more of the following factor s: (i) the tapeworm protective antigens were not pre sent initially in most of the preparations injected or that they were pre sent in too Iowa quantity to stimulate immunity (ii) the worm protective antigens were highly labile and they were destroyed during preparation, probably by enzymes released by the disintegrating worms themselves, or inactivated by chemical reactions in the stomach or intestine when the se preparations were given orally or intraduodenally. (iii) . -the physicochemical characteristic s of the se protective antigens had been altered during preparation (iv) the presence of a wide array of worm antigens, e. g. in a homogenate, dissipated the host immune response and masked the presence of the protective antigens possibly as a result of antigenic competition (v) the route of antigen administration was the crucial factor that militated against the induction of functional immunity rather than the antigens themselves (vi) the duration of antigenic stimulation was not long enough and a longer period. analogous to that required for the development of immunity from an enteric H. diminuta infection, was needed (vii) the regimes of vaccination described were conducive to the induction of tolerance. To elucidate the validity of these assumptions, experiments were carried out with live worm antigens. The rationale behind each approach is described separately in the text. Strobilate a-day-old worms. apparently capable of surviving for appreciable periods of time when implanted subcutaneously or intraperitoneally, did not immunize mice against challenge. Implantation of a strobilate 8-day- day old worm surgically into the duodenum conferred only weak protection. The in vivo process of excystation, which is by passed when immunization is performed by implantation of worms directly into the duodenum, had no influence on the ability of the worm to stimulate immunity. The se findings suggest that the failure to induce strong immunity by parenteral implantation of a live a-day-old was possibly due to -the fact that the 8-day- old worm is, in itself, inefficient in inducing a pronounced protective response against challenge, even when presented enter ally • The fact that a weak protective response was induced by the intraduodenal administration of the 8-day-old worm and not by parenteral implantation of the se worm s suggests that the enteric route is more efficient in the induction of functional immunity against the tapeworm than either the subcutaneous or intraperitoneal routes. In other experiments it was established that the young worm is more efficient in the stimulation of protective immunity against challenge than older worms. It is of interest that the older worms, when implanted surgically into the duodenum, pre sent the host with significantly larger amounts of strobili antigens per unit time than do the younger ones. This observation casts doubt on the significance of the strobila as the major source of H. diminuta protective antigens . The logical explanation for the failure to immunize mice by vaccination with the killed worm antigens is that this is possibly because the antigens used were derived mainly from strobilar tis sue obtained from worms even older than the 8-day-old parasites whose poor immunizing potential was demonstrated. Live excysted worms, which provide only scolex and neck antigens J were capable of inducing a protective response when administered intraperitoneally. Irradiated worms, incapable of growing strobilae, were as immunogenic as worms of the same age which were not irradiated. Immunization of mice with an irradiated vaccine is advantageous in the sense that the immunizing infection can be denoted as self-limiting resulting in the prevention of propagation of the parasite to the intermediate host, at a time when specific protective immunity is raised in the definitive host. Two independent investigations were undertaken to locate the origin of H. diminuta protective antigens. The technique s of chemical abbreviation of immunizing infections and irradiation were used for this purpose. The re suits provided evidence that the induction of functional immunity against H. diminuta in mice is independent of the presence of a strobila: is determined by the duration of an antig e nic stimulus deriving from the scolex and/or neck regions. The degree of this immunity is also determined by the number of worms in the immunizing infection. The conclusions drawn from the present investigation as to the origin of H. diminuta protective antigens and the immunogenic potential of irradiated worms are at variance with those reached by other investigators. In the second part of this thesis the mechanism of the immunologically based rejection of Raillietina cesticillus from chickens was investigated. Chickens whose ability to produce antibodies was abrogated by bur sectomy and irradiation developed protective immunity against the tapeworm as did the controls with specific anti-worm antibodies in their sera. It is suggested that antibody is not the crucial component of the mechanism affecting the growth and development of R. cesticillus in the immune chicken.