The influence of the site of parasite inoculation on the development of Th1 and Th2 type immune responses in (BALB/c × C57BL/6) F1 mice infected with Leishmania major

Although inbred strains of mice are classified as genetically resistant or susceptible to Leishmania major based upon their ability to control infection, other factors such as the strain, dose, and site of parasite inoculation can also affect the outcome of the disease. Here we used the Fl progeny of BALB/c (susceptible) and C57BL/6 (resistant) mice (designated CB6F1) to investigate whether mice or intermediate susceptibility to infection differed from the parental strains in their ability to control infections at different cutaneous sites. CB6F1 mice developed progressive disease when inoculated in the dorsal skin, but healed infections in the footpad. Consistent with these observations, mice inoculated in the footpad ultimately developed Th1 responses, known to be required for healing, while Th2 responses developed in mice inoculated in the dorsal skin. However, IL-4 and IFN-γ production during the first few weeks of infection was similar in CB6F1 mice inoculated at either site, suggesting that factors in addition to the relative levels of these cytokines produced early in infection may influence the nature of the antileishmanial immune response, and the eventual disease outcome. Infection in CB6F1 mice provides a model for the study of immunity to L. major in genetically identical animals, in which a prolonged mixed Thl/Th2 cytokine pattern initially develops, but ultimately diverges into more defined Th1 and Thl type responses.     

THE CHEMISTRY AND CONFORMATIONAL AND BIOLOGICAL ANALYSIS OF VITAMIN D3, ITS METABOLITES AND ANALOGUES

The chemical properties, sterochemical relationships and solution confromation, as assessed in part by proton NMR spectroscopy, for vitamin D₃, its major metabolites [including 1α, 25-(OH)₂ D₃, its hormonally active form] and a number of A-ring and side chain analogues are evaluated and discussed in relation ot their biological activity. In particular the relative ability of many of these seco-steroids to compet both with 25-OHD₃ for its chick serum binding protein and 1α, 25-(OH)₂-D₃ for its chick intenstinal cytosol-chromation receptor systme was quantitated, in vitro , Further, the relative effectiveness of all these metabolites and analogues to mediate in vivo intestinal calcium absorption and bone calcium mobilization was determined. Collectiveily these chemical and bilogical studies constitute a 'systems analysis'of the various steroid structural parameters both required and tolerated by the multi-stepped endocrine system associated with the bilogical actions of vitamin D.