The immune response of the mouse to the tapeworm Hymenolepsis diminuta

Bland, Paul William (1976) The immune response of the mouse to the tapeworm Hymenolepsis diminuta. PhD thesis, University of Glasgow.

Abstract

Previous investigations have demonstrated that the cestode, Hymenolepis diminuta, is rejected immnologically from the mouse small intestine. This host-parasite relationship provides a model for the study of immunity to adult tapeworms which were formerly thought to be immunologically inert. The work described herein was undertaken to investigate the specific mechanisms underlying the response of the mouse to H. diminuta and to deter-mine the possible effect of the response on a physiological aspect o of the host-parasite relationship. Whole-body X-iradiation of the mouse was used extensively as a tool to deplete the immune response and induce suppression of worm rejection. Initial investigations using single cysticercoid infections of H. diminuta in random-bred mice indicated that effective suppression of worm rejection was achieved with either lethal or sublethal doses of X-irradiation. Succeeding investigations (which employed five- or six-cysticercoid infections in inbred mice to reduce variation), therefore, used only sublethal doses of irradiation to eliminate the necessity for subsequent reconstitution of the haemopoietic tissues. Growth of H. diminuta following irradiation given early in infection was found to be less than growth following irradiation given later in infection. The response inducing worm rejection was found to be biphasic with respect to radiation sensitivity; irradiation on or before day 8 post-infection effectively suppressed worm rejection, whilst irradiation on day 10 had no effect on the normal course of worm rejection . Restoration of the irradiation-depleted response was attempted using various combinations of lymphoid and bone-marrow cells, but reconstitution was not achieved using any of the cell combinations. It is suggested that X-irradiation induces a defect additional to simple depletion of small lymphoid elements and that, in particular, local antibody production in the intestine of infected mice be investigated following irradiation. The unresponsiveness of athymic nude mice and adult-thymectomised, irradiated, bone-marrow reconstituted mice to single H. diminuta infection demonstrates that the response inducing rejection of H. diminuta requires the presence of fully differentiated T cells. Total weight of worms recovered from nude mice infected with 10 cysticercoids of gr diminuta. was less than from single worm infections in nude mice, suggesting the presence of a threshold of immunological stimulation dependent on surface area of worm rather than on worm weight. The effect of intestinal inflammation, induced by Trichinella spiralis, on a concurrent infection with H. diminuta was investigated. It was demonstrated that no cross-immunity exists between the two parasites. The inflammatory response produced marked adverse effects, on H. diminuta manifested variously by reduced worm growth, destrobilation and worm rejection from both mice and rats. The severity of the effect on H. diminuta was shown to be dependent on the timing of acute inflammation with respect to development of H. diminuta. In the mouse, if severe inflammation occurred at, or shortly following the time of infection with H. diminuta then, although many H. diminuta established and survived for at least 2 days, they did not grow and the majority were subsequently expelled. If, however, H. diminuta was allowed xvi to establish for 5 or 6 clays prior to the appearance of severe inflammation, then although the worms destrobilated, most survived the inflammatory response. In the rat, growth of H. diminuta was stopped by the inflammatory response to Ta spiralis. However, when the inflammation subsided, worm growth recommenced and eventually returned to levels found in non-inflamed controls. It is suggested that future work should investigate the specific nature of this interaction and should include careful monitoring, not only of cellular and biochemical changes occurring during the inflammatory response, but also of host dietary intake during the response. Brief discussion is made of the possible sites of immune damage to H. diminuta and investigation of one such site, the transport of nutrients across the tapeworm tegument, is described. The transport of 14C-labelled glucose, acetate and methionine, which cross the tegument by separate pathways, was investigated. Transport of these substrates by worms from six-cysticercoid infections in mice was compared to transport by worms of similar weight from mice immunosuppressed with cortisone and from rats. Transport of methionine and acetate by H. diminuta from untreated mice was depressed compared to transport by worms from immunosup-pressed mice or rats. Uptake of glucose was similar, regardless of host type. The results are interpreted to demonstrate the selective blocking of membrane transport loci on the tegument of H. diminuta from mice by an immunological mediator. The thesis adds to current concepts of immune responses to adult cestodes and suggests many lines of further investigation.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Additional Information: Adviser: C A Hopkins
• Keywords: Parasitology
• Date of Award: 1976
• Depositing User: Enlighten Team
• Unique ID: glathesis:1976-72957
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 11 Jun 2019 11:06
• Last Modified: 11 Jun 2019 11:06
• URI: https://theses.gla.ac.uk/id/eprint/72957