Lawrence, Catherine Elizabeth
(1990)
The immunobiology of Heligmosomoides polygyrus in the murine host.
PhD thesis, University of Nottingham.
Abstract
The development of the gastrointestinal nematode Heligmosomoides polygyrus (syn. Nematospiroides dubius) in the mouse was studied. The stage specific production of acetylcholinesterase was measured in both excretory/ secretory products and in worm homogenates and found to be maximal between days 4-6 post infection, corresponding to the fourth larval stage of the parasite's life cycle.
Analysis of the proteolytic enzymes found in the same preparations of the parasite again revealed a stage specific release. Quantitative examination showed a maximum concentration of proteolytic enzymes in the early third larval stage, whilst qualitative analysis revealed a number of molecules at 96, 76, 42, 33, 18, 16, and 13 kDa in the early stages, which gradually disappeared as the parasite aged until only those at 76, 18, 16, 13 kDa remained by day 120.
The molecules present on the surface of the various stages of the parasite were extracted using a number of procedures. Various stage specific surface molecules were identified as were two possible sex specific molecules at 76 and 145 kDa.
The immune response to a primary infection of the parasite was characterised in three strains of mice with different degrees of susceptibility to infection (SJL, BALB/c and CBA). It was noted that the better the strain was at expelling the parasite, the greater and swifter was the response as assessed through the use of a number of criteria. These included white blood cell counts, differential cell counts, the Band T cellularity of the secondary lymphoid organs, the response of these cells to mitogens, the mucosal mast cell response, quantitative antibody response (Mancini and ELISA) and qualitative antibody response to parasite antigens (immunoblot). In each case SJL responded better than BALB/c which, in turn responded to higher degree than CBA.
Functional host protective immunity was stimulated in the same three strains of mice using a challenge infection following a 9-day anthelmintic abbreviated infection. The same criteria were used to measure the immune response to the parasite as for the primary infection and, as for the primary infection, it was found that the high responder strains gave a more rapid and more intense reaction to the parasite than the low responder strain. Immunisation prevented the establishment of a proportion of the challenge infection and also resulted in the premature expulsion of parasites.
The parasite surface molecules which were recognised by mice undergoing either a primary infection or an immunising infection were identified. It was revealed that molecules at 208, 145, 92, 76 and 62 kDa on adult parasites were recognised by mice which had expelled a primary infection. Mice which were immune to a challenge infection recognised molecules at 62 and 20-15 kDa on larval parasites. A molecule at 30.5 kDa was also recognised by immune mice and corresponded to the molecular weight of acetylcholinesterase in the ES.
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