Workshop 1G: Genetics of host susceptibility and selection for resistance

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R. C. A. THOMPSON

mechanisms of immune evasion: antigenic variation, stage specificity of antigens, molecular mimicry, antigen masquerade, or immune intervention by parasites. WORKSHOP 1F: PROTOZOAN ANTIGENS AND

GENES P. J. MYLER*and R. COPPELt * Issaquah Health Research Institute, 1595 NW Gilman Blvd, Issaquah, WA 98027, U.S.A. t Walter & Eliza Hall Institute, Parkville, Victoria, Australia Many interesting papers dealing with a number of different protozoa were presented during this workshop. Several papers concerned the circumsporozoite protein (CSP) of different Plasmodium species. Computer modelling of the theoretical 3-dimensional structure of the 4 amino acid repeat of P. falciparum CSP indicated a helical structure of 12 amino acids per turn (Abstract No. 755). Antigens of MW 55K and 35K were identified as CSP receptors on hepatoma cells (no. 20). The repeat sequence was not involved in the binding. The repeat sequence was found to vary considerably within a single species, P. cynomolgi (no. 765). Other sporozoite antigens have been described and cloned in P. yoelii (no. 128). The identification and cloning of numerous antigens from the blood stages of P. falciparum was described by several groups. These antigens included MESA, RESA and HRP (nos. 156 & 99), rhoptry antigens (nos. 205 & 106) and gp185 (no. 302). Cross-strain antibody reaction to the conserved, non-repeat region of gp185 was observed. Separation of the chromosomes of P. falciparum and Giardia on orthogonal field alternation gel electrophoresis (OFAGE) and uniform field electrophoresis was described (no. 676). A 55K antigen from the surface of Babesia divergens was found to be partially protective after vaccination (no. 716). The antigens of Sarcocystis spp. were characterized using monoclonal antibodies (McAbs) and immuno-electron microscopy (nos. 103 & 486). The surface antigens of Trichomonas vaginalis and Tritrichomonas foetus were similarly analysed (no. 672). A 67K surface antigen of Theilaria parva sporozoites recognized by neutralizing antibodies was described (no. 474). Toxoplasma gondii exoantigens were shown to differ between the tachyzoite and bradyzoite stages (no. 60). rRNA from Toxoplasma and Hammondia were found to be extremely similar (no. 328). In the trypanosomatids, analysis of B-tubulin orphons indicated restriction enzyme polymorphisms between different strains of T. cruzi (no. 74). The inhibitor of DNA repair, 3-aminobenzamide, was found not to affect the rate of antigenic switching of T. brucei in vitro (no. 383). Genomic rearrangements, at the level of VSG genes and chromosomes, associated with antigenic switching were characterized (no. 475). A 46K integral membrane glycoprotein antigen

from Leishmania mexicana amazonensis was characterized (no. 338). The cloning of several antigens from L. donovani (nos. 74 & 286) and a developmentally regulated gene from L. major (no. 360) were described. The use of fractionated glycolipids in an RIA resulted in improved ability to differentiate L. major infections (no. 415). The characterization of several antigens from the surface of Entamoeba histolytica using McAbs was presented. WORKSHOP IG: GENETICS OF HOST SUSCEPTIBILITYAND SELECTION FOR RESISTANCE D. WAKELm*and C. DOBSONt * University Park, University of Nottingham, U.K. t Department of Parasitology, University of Queensland, St Lucia, Queensland, Australia The realization that the relationship between a particular species of parasite and its host is influenced by genetically-determined variations in the host is not new, but it is the basis of an area of parasitologlcal research which has undergone an explosive development of interest during recent years. Host variation exists in all the parameters that determine the success or failure of a host-parasite relationship, but attention has been concentrated upon variation in immunological and immunologically-mediated responses. The papers presented in the workshop reflect this emphasis, but the other components relevant to parasite survival were not entirely forgotten. C.R. Brockelman, P. Tan-ariya and B. Wongsattagarond described an in vitro micro test to investigate the effects of the abnormal haemoglobins of thalassaemic individuals upon the growth and survival of Plasmodium falcipamm. They showed that all four types of thalassaemia studied were associated with inhibitory effects upon the parasite. S. Geerts et al. described interesting observations on the survival and development of Taenia saginata in jirds (Meriones unguiculatus). An overall infection rate of 5.1% was achieved when oncospheres were injected subcutaneously, and the cysts developing were apparently normal, evaginating when placed in 10% bile. Splenectomy of the host increased the success of development to 13.3%. The ability to initiate development of this human-specific tapeworm in a laboratory host is obviously an important achievement. The remainder of the papers presented were primarily concerned with questions of immunologically-based resistance and susceptibility, and described a variety of experimental systems and approaches. M. Belosevic and G. M. Faubert discussed the use of in vitro assays for antibody-mediated parasite immobilization and lysis in analysis of mouse strain variation in response to Giardia muris. A/J and B/10 mice support very different patterns of infection, but each produces antibody capable of anti-parasite activity and no difference could be determined between the strains in this parameter. M. Olivier and C.E. Tanner used Cyclosporin A, a selective T cell modulator, to

Post Congress Scientific Report explore the relationship between T cell activity and mouse strain variation in infection patterns with Leishmania donovani. The susceptibility of C57 BL/ 6J mice was maintained, relative to C57 L/J, even when both were treated with CSA, but levels of infection were higher than in untreated controls. W. K. Kroeze and C. E. Tanner used the same mouse strains in an analysis of the basis of mouse susceptibility to Echinococcus multilocularis. Susceptible C57 L/J mice showed less efficient inflammatory responses (measured in numbers of myeloperoxidase-positive cells) and it was suggested that failure to recruit such cells to inflammatory foci may contribute to susceptibility. Another facet of variation in inflammatory responsiveness was the subject of the paper by K. Yoshimura and K. Ishida. Guinea pigs, which are nonpermissive hosts for the nematode Angiostrongylus cantonensis, produced marked eosinophilia after transfer of live adult worms into the pulmonary artery; no IgE or haemagglutinating antibody response was detected however. Permissive rat hosts, in contrast, showed no eosinophilia after transfer. An important finding was that this host species difference was also apparent after presentation of soluble worm antigens (extract or ES) by infection or via an osmotic minipump. Worm extract also stimulated an eosinophilia in the non-permissive mouse host, both normal and nude strains. The immunological basis of mouse strain variation in response to Eimeria vermiformis was analysed by H. S. Joysey, M. E. Rose and D. Wakelin, using the techniques of adoptive transfer and of radiation chimaera construction. Both T and B lymphocytes transfer immunity, but large numbers of cells are necessary. The response of susceptible strains can be improved by transfer. Radiation chimaeras show the phenotype of the bone marrow donor used. Four papers presented data on host variation in domestic stock. R. B. Dolan and A. R. Njogu discussed acquired and innate resistance to trypanosomiasis in Kertyan Boran cattle. Orma Borans, herded by African tribesmen, are trypano-tolerant; Borans selected by white farmers for increased productivity are not. In a controlled experiment no evidence was obtained that previous exposure affected response to further challenge in either breed, but there was evidence for innate differences. The tolerant breed showed greater ability to limit the number of severe infection episodes, this ability being heritable with an estimated repeatability of 0.24. It was suggested that selection for productivity per se would be a useful means of improving overall resistance to infection. Selection for resistance of sheep to gastro-intestinal nematodes was discussed by R. G. Windon, J. K. Dineen and H. J. S. Dawkins, and by G. G. Riffkin and W. K. Yong. The former showed that selection for resistance to Trichostrongylus colubriformis, after vaccination with irradiated larvae, produced high- and low-responder lines. High responders showed resistance to other GI species, expressed resistance under field conditions

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and maintained productivity. They exhibited an improved overall immunological and inflammatory competence. Riffldn described the use of peripheral blood lymphocyte transformation, in response to worm antigen, as a predictive test for resistance to Ostertagia circumcincta and T. colubriformis. In ewes classified as high- or low-responders on the basis of faecal egg count there was a good correlation with stimulation index. Lambs from these ewes, from the same ram, showed levels of resistance which broadly correlated with their pre-infection stimulation index. Yong and Riffkin then described the range of antigens recognized serologically by high responder sheep, using P A G E and immunoblotting techniques. Four antigens, from a total of more than 60, appeared to be selectively recognized by sheep showing greater resistance. WORKSHOP 1H: BIOCHEMISTRY OF HELMINTHS

J. BARRETT* and C. BRVANTt * Department of Zoology, University College of Wales, Aberystwyth, Wales t Department of Zoology, Australian National University, Canberra, A.C.T., Australia There were 24 presentations, covering metabolism, enzymology, developmental processes, surface membrane phenomena and analytical and applied biochemistry. The majority of the papers were concerned with energy metabolism and catabolic reactions. NMR provides a non-invasive method of studying parasite metabolism and two papers dealt with the application of this technique to glucose metabolism in Hymenolepis diminuta and Fasciola hepatica (C. A. Behm, C. Bryant and A.J. Jones; M. Novak, W.C. Evans, H. M. Hutton and B. J. Blackburn). S. Kohlhagen and C. Bryant reported high levels of glycerol catabolism in cestodes from carnivorous hosts and pointed to a correlation between glycerol utilization and the presence of a FBP insensitive pyruvate kinase. The problem of strain variation in metabolism was dealt with by E. M. Bennet, C. A. Behm and C. Bryant who found that different strains of Heligmosomoides differed in their capacities to shift from aerobic to anaerobic metabolism. Detailed analysis of the kinetic properties of parasite enzymes is crucial to our understanding of control mechanisms. S. E. Wages and L. S. Roberts reported on the control of glycogen synthase and glycogen phosphorylase by exogeneous glucose in H. diminuta. The kinetic properties of lactate dehydrogenase from Echinococcus were described by T. Duriez, A. F. Petavy, E. Sarciron and Lodiha M'Boyd, whilst S. M. A. Abidi and W . A . Nizami reported on the electrophoretic and kinetic properties of glutamate dehydrogenase from amphistomes. F. Kawamoto and N. Kumada described the regulatory roles of calcium and protein kinase on the development of Mesocestoides larvae. The role of oxidative processes in helminth parasites is still very poorly understood. S. Kohlhagen