Intestinal immune responses of mice to the tapeworms Hymenolepis diminuta and H. microstoma

Befus, Albert Dean (1975) Intestinal immune responses of mice to the tapeworms Hymenolepis diminuta and H. microstoma. PhD thesis, University of Glasgow.

Abstract

Previous investigations suggested that adult cestodes do not evoke host immune responses such as those directed against intestinal nematodes, but this is not so and the recent demonstration that Hymenolepis diminuta is expelled from mice by an immunological mechanism provides an excellent model system with which to investigate these responses, H, microstoma provides an interesting comparison with diminuta as, in the mouse, the former survives well despite host immune responses. Following the initial administration of one (Ic) or six (6c) cysticercoids to mice, >80% of H, diminuta can be recovered 8 to 10 days later, but thereafter, worm rejection commences. Prior to rejection, worms grow rapidly. Herein the term 'rejection' includes both destrobilation (loss of the strobila) and expulsion, although only some worms destrobilate prior to being expelled. For objective analyses of the dynamics of infection the following criteria are established: 1) mean survival time - the first day on which >50% of the worms administered had been lost or destrobilated, 2) destrobilated worm - a worm <0,2 mg dry weight on da 10 or thereafter, and 3) biomass - the total dry weight of all worms recovered on a given day from a group of mice (worms <0,1 included as 0,1 mg), The mean survival time of 1c primary infections in 6 week old CFLP and NIH male mice can vary from 12 to 18 days but normally was 14-16 days, whereas with 6c infections the raean survival time was invariably 12 days. Worms grow more slowly in 6c than in 1c infections, a well known phenomenon called 'crowding' and previously attributed solely to inter-worm competition for nutrient. However, it may be largely due to potentiated host immune responses in the multiple (6c), more immunogenic, infections. In young, relatively immunologically immature mice (2-4 weeks old at infection), rejection of 1c infections occurs, but is delayed in comparison with infections in older, relatively immunologically mature, mice (5-7 weeks old). Biomass, which combines both worm survival and growth, shows clearly the relative immunological unresponsiveness of young mice to H, diminuta. The unresponsiveness is due to a quantitative rather than an absolute immunological deficiency and the increasing responsiveness of mice to H, diminuta with age correlates well with the maturation of intestinal lymphoid tissue. Mice >7 weeks old may be more responsive than the 2-7 weeks old mice studied herein. Following the natural termination of a primary infection, an enhanced response occurs to secondary infection which is expressed as stunting of the worms. The severity of stunting is directly related to the intensity of the primary and secondary infections, Furthermore, when the primary infection is terminated after 3 days by anthelmintic only limited stunting of secondary worms can be detected, but following a primary infection terminated after 12 days stunting of secondary worms is severe. As protective immunity to H. diminuta is expressed in the lumen of the intestine, a precis of intestinal immune responses is given and double immunodiffusion, single radial immunodiffusion and direct anti-globulin immunofluorescence were used to study the intestinal immune responses of infected mice. No anti H, diminuta antibodies were detected in the sera or intestinal contents of infected or resistant mice and no consistent differences were detected between infected and uninfected mice in the levels of IgA, IgG1, IgG2 and IgM in the sera or intestinal contents. However, all these immunoglobulins occur on the tegument of both H. diminuta and H, microstoma and are probably specific antibodies combining with the antigens which are in the tegument. The third component of complement (C3) was detected fixed to the tegument of H. diminuta but not to H. microstoma although this result is equivocal. The morphology and occurrence of darkened areas in the tegument of H. diminuta are described and it is concluded that they are sites of immunological damage to the worm perhaps induced by the tegument bound antibody and C3. The results are discussed in relation to protective immunity and survival mechanisms of intestinal helminths. The thesis provides essential information for the further characterization of immunity to H. diminuta and strongly urges that knowledge of protective immunity to adult cestodes will be of considerable medical significance.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Additional Information: Adviser: C A Hopkins
• Keywords: Immunology, Parasitology
• Date of Award: 1975
• Depositing User: Enlighten Team
• Unique ID: glathesis:1975-73108
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 14 Jun 2019 08:56
• Last Modified: 14 Jun 2019 08:56
• URI: https://theses.gla.ac.uk/id/eprint/73108