Investigations have been made into the genetic control of immunity to the nematode Trichuris muris. Both background genes and genes within the mouse major histocompatibility complex (MHC), H-2, were shown to influence the expulsion of T. muris with the former having the stronger influence. At least two genes within the H-2 complex determined response phenotypes, the effects of "resistance" or "susceptibility" alleles at I-A being modulated by resistance or susceptibility alleles at aD end locus/loci. Differential responsiveness within slowly responding mouse strains suggested that parasite-dependent effects were also important. The primary antibody response to T. muris excretory/secretory (E/S) antigen, predominantly an IgG response, was also shown to be controlled by background and H-2-linked genes. In general, mouse strains less resistant to infection developed higher levels of IgG than- more resistant strains of mice. However strains of mice possessing the H-2q haplotype, irrespective of their genetic background, rapidly developed higher levels of IgG1 antibodies than strains of other haplotypes, H-2q haplotype mice tending to be more resistant to infection. Recognition of two high molecular weight (MW) E/S antigens by IgG as revealed by immunoprecipitation was also found to be almost exclusively H-2q restricted. This restriction may be partly quantitative but as such would operate in vivo due to the restriction on the ability to produce high levels of specific IgG. Both H-2q restricted phenomena may be part of, but not absolute requirements for, protective immunity. Parasite-induced effects on host immunity were also studied. Later larval and adult stages of T. muris were shown to be immunosuppressive, immunosuppression being long lasting and preventing the expulsion of subsequent infections. Vaccination with E/S antigen was shown to protect strains of mice which are slow to expel worms (poor-responder) or totally unable to expel worms (non-responder) from a primary infection with T. muris. However protection was slow to be expressed. Antigen recognition profiles of vaccinated strains of mice differed from their primary infection recognition profiles and included the recognition of the two high MW antigens shown to be H-2q restricted in a primary infection. Thus altering the mode or route of E/S antigen presentation may lead to shifts in responsiveness of H-2 genotypes to specific determinants and/or boost specific antibody levels sufficiently to reveal recognition of these antigens. Prior experience of a patent primary infection prevented vaccination protecting non-responder mice against subsequent infections. This inability was correlated with suppressed IgG1 antibody levels and failure to recognise three high MW antigens including the IL-2q restricted antigens. Using a panel of monoclonal antibodies raised against E/S antigen it was shown that E/S antigens, apparently including both immunogenic and immunosuppressive molecules, were localised to granules within the stichocyte cytoplasm of the adult T. muris stichosome.

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.