This review summarizes the personal experiences of the authors and their colleagues during ten years of field and laboratory studies on human immunity to Schistosoma mansoni infections. There is evidence for the very slow development with age of an acquired resistance to reinfection (demonstrable after chemotherapy of the primary infection) distinguishable from a lack of reinfection due to reduced exposure. The implications of this immunity for the design of chemotherapy programs targeted at infected schoolchildren are discussed. Observational studies on the mechanisms of immunity have demonstrated a marked helminthocidal capacity of eosinophils. Subsequent correlative studies have indicated a role of IgM and IgG2 "blocking" antibodies in maintaining the continued susceptibility of young children, and of IgE antibodies in mediating protection in older individuals. Some problems in studying human immunity, and the implications for vaccine development, are also discussed.
Clostridum thermosaccharolyticum and Clostridiurm thermohydrosulfuricum possess as outermost cell wall layer a tetragonal or hexagonal ordered array of macromolecules. The subunits of the surface layer can be detaqhed from isolated. cell walls with urea (8 M) or guanidine-HCl (4 to 5 M). Triton X-100, dithiothreitol, ethylenediaminetetraacetate, and KCl (3 M) had no visible effect on the regular arrays. Sodium dodecyl sulfate-polyacrylamide electrophroesis showed that, in both organisms, the surface layer is composed of glycoprotein of molecular weight 140,000. The glycoprotein from both microorganisms has a predominantly acidic amino acid composition and an acidic isoelectric point after isoelectric focusing on polyacrylamide gels. The glycocomponent is composed of glucose, galactose, mannose, and rhamnose.
1. The name ;bactoprenol' has been given to the most abundant lipid formed by three species of lactobacilli from mevalonic acid. 2. A method for the preparation of pure bactoprenol is described. 3. The thin-layer chromatographic properties of bactoprenol and of its acetylated and hydrogenated derivatives resembled those of dolichol. 4. Analysis by mass spectrometry and by nuclear magnetic resonance showed that the molecule is formed by condensation of 10 unsaturated isoprene units and 1 saturated isoprene unit. 5. Its molecular weight is 768 and it has 10 double bonds/molecule. 6. Infrared spectroscopy and the uptake of acetyl groups indicated that the molecule contains a hydroxyl group. 7. It is concluded that bactoprenol is a C(55) isoprenoid alcohol.
The bacteriolytic and bactericidal effects of the human proteinases cathepsin B, cathepsin D, cathepsin G, and elastase were investigated. Cathepsin G and elastase were 5 to 10% as active as egg white lysozyme in the lysis of Micrococcus lysodeikticus. All four enzymes slowly lysed the lysozyme-resistant Staphylococcus aureus. The gram-negative Acinetobacter 199A was rendered sensitive to lysozyme by all of the proteinases. Only elastase caused marked proteolysis of the outer membrane, which would permit access by lysozyme to the underlying peptidoglycan. When the surface layer of regularly arranged a protein was removed, however, the outer membrane proteins became susceptible to the other proteinases. Cathepsin G, elastase, and cathepsin D were bactericidal to Acinetobacter 199A. The bactericidal activity of cathepsin D was shown to be dependent on enzymatic activity, unlike that of cathepsin G, which was related to its cationic nature.
We report the use of a matched set of mice/human chimaeric antibodies, directed against the 5-iodo-4-hydroxyl-3-nitrophenacetyl (NIP) hapten, to investigate the roles of different human isotypes in antibody-mediated eosinophil-dependent killing of schistosomula. The chimaeric antibodies consist of mouse VH, VL and CL regions with human gamma 1, gamma 2, gamma 3 (2 allotypes), gamma 4, alpha 2, mu or epsilon CH regions and were used in in vitro assays with human eosinophils and NIP-coated S. mansoni schistosomula. Some anti-NIP isotypes mediated high levels of killing, which was specific for NIP-coated larvae, and we suggest that these antibodies will be a valuable tool for studies on the role of antibody isotypes in anti-schistosome immune effector mechanisms. In particular, this method directly demonstrated, for the first time, that IgA is highly effective in mediating the killing of metazoan parasites by human eosinophils.
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