Genetic resistance to Candida albicans infection is conferred by cells derived from the bone marrow.
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Biomedical subjects
Publications and source records attributed to R B Ashman.
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To determine whether mature humeral cortical bone would be modified significantly by an acute exposure to weightlessness, adult rats (110 days old) were subjected to 14 days of microgravity on the COSMOS 2044 biosatellite. There were no significant changes in peak force, stiffness, energy to failure, and displacement at failure in the flight rats compared with ground-based controls. Concentrations and contents of hydroxyproline, calcium, and mature stable hydroxylysylpyridinoline and lysylpyridinoline collagen cross-links remained unchanged after spaceflight. Bone lengths, cortical and endosteal areas, and regional thicknesses showed no significant differences between flight animals and ground controls. Our findings suggest that responsiveness of cortical bone to microgravity is less pronounced in adult rats than in previous spaceflight experiments in which young growing animals were used. We hypothesize that 14 days of spaceflight may not be sufficient to impact the biochemical and biomechanical properties of cortical bone in the mature rat skeleton.
An ultrasound reflection technique was designed and implemented to study the mechanical properties of bone material. The technique uses the fact that an ultrasound beam produced in water undergoes total internal reflection off a bone sample at a critical angle formally related to the velocity of a pressure wave in bone. When the plane of scattering is rotated around the normal to the sample surface, the critical angle varies with a periodic dependence dictated by the intrinsic symmetry of the bone structure at the point being examined. Most current measurements of sound velocity are made using transmission techniques. A double-blind intercomparison between this technique and a transmission technique, which was previously validated against tensile mechanical testing, was performed for samples of isotropic materials and of human cortical bone. Strong correlations were found for both sets of samples. For the isotropic materials the velocities were approximately equal, but for bone they were on average 11% higher in reflection than in transmission. This was the result both of the higher frequency employed in reflection (3.5 rather than 2.25 MHz) and of the different effects of sample imperfections on the two measurements. In particular, the reflection technique used in this work studied the surface of the sample, but the ultrasound beam in the transmission method propagated through its interior. In assessing the mechanical properties of bone specimens by ultrasound, the reflection technique samples a discrete bone surface element and the transmission method analyzes the entire volume of the specimen. Thus the reflection technique may yield a measure of the mechanical property of bone trabeculae that is largely unaffected by the mass of the entire specimen, but mass and the structural density of the specimen affect the transmission method.
In oral infections with the yeast Candida albicans, the expression of MHC class II antigens on keratinocytes has been reported to be enhanced. In the present experiments, exposure to C. albicans or its products in vitro was found to increase the expression of class II MHC antigens on thioglycollate-induced mouse macrophages, and on LK cells (an antigen-presenting cell line). The implications of this finding for the understanding of immunoregulation and susceptibility to C. albicans infection are discussed.
Mice deficient in the fifth component of complement are known to be extremely susceptible to lethal challenge with Candida albicans. However, male mice, that have significantly higher concentrations of serum C5 than females, were markedly more susceptible to infection. This difference was observed in both susceptible (CBA/H) and resistant (BALB/c) mice. Levels of serum C3 likewise showed no correlation with susceptibility.
The yeast Candida albicans is a recognized, though uncommon, cause of osteomyelitis in humans. In a mouse model of systemic candidiasis, osteomyelitis has been found to occur in the vicinity of the inner ear, and to persist for at least 6 months after the initial infection.
The beige mutation in mice has a pervasive effect on mechanisms of host resistance to infectious agents. Best characterized are defects in granulocyte chemotaxis and phagocytosis, which are associated with increased susceptibility to bacteria, and a deficiency in the levels of natural killer (NK) cells, which has been linked to decreased resistance to both murine cytomegalovirus and the yeast Cryptococcus neoformans. The objective of the present experiments was to explore the cellular basis of the enhanced susceptibility of beige mice to systemic infection with the yeast Candida albicans. In contrast to murine cytomegalovirus and C. neoformans, infection with C. albicans did not induce any detectable NK cell activity in the spleen of bg/bg or bg/+ mice. Unfractionated bone marrow (BM) displayed some candidacidal activity, mediated by both phagocytic and nonphagocytic cells; however, there was no difference between homozygous and heterozygous mice in the effector function of normal BM cells or mononuclear cells derived from either short- or long-term BM cultures. On the other hand, peritoneal granulocytes from bg/bg mice were significantly more effective than those from bg/+ mice in killing Candida blastoconidia in vitro. A similar comparison of granulocytes from short-term BM cultures showed that the activities of cells from bg/bg and bg/+ mice were equivalent, indicating that the granulocytes derived from the peritoneal cavity of bg/bg mice had probably been exposed to some form of nonspecific stimulation in vivo. Somewhat surprisingly, long-term BM cultures did not support the continual growth of bg/bg granulocytes, and it is possible that the beige mutation may be associated with a lesion in the differentiation pathway that leads to the production of granulocytes. Taken together, the data indicate that, in beige mice, granulocytes rather than NK cells are a major determinant of natural resistance to C. albicans infections.
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We demonstrate here: (a) the existence of T helper (Th) cells that augment the generation of virus-specific cytotoxic T cells in vitro, (b) that the helper cells carry the theta and Ly 1 membrane antigens, (c) that activation of the Th effect is specific for viral antigens, and (d) that the delivery of help is not H-2 restricted.
Two different BALB/c anti-CBA (H-2k)monoclonal antibodies that bind to Kk and Dk antigens blocked Tc cell-mediated lysis of L929 (Kk, Dk) target cells, but with quite different specificity. One antibody (30R3) powerfully blocked Kk-specific lysis mediated by alloreactive or Kk-restricted Tc cells immune to ectromelia, Sendai, or influenza viruses. The other antibody (27R9) blocked these anti-Kk Tc cells much less than 30R3, but in contrast, 27R9 blocked anti-Dk lysis much more than 30R3. Most importantly, 27R9 strongly blocked Dk-restricted anti-influenza Tc cells, but did not significantly block Dk-restricted anti-Bebaru (BEB) lysis. This result indicated that different H-2 determinants coded in the D end of H-2k were recognized by influenza-and BEB-immune Tc cells. These determinants may be carried on two different molecules coded by the H-2D and H-2L loci, but other possibilities are not yet excluded.
Leucocytes from purified protein derivative (PPD) skin test positive individuals, after exposure to PPD in vitro, show a significant increase in nitroblue tetrazolium (NBT) dye reduction when compared to leucocytes from PPD negative donors. The active principle was shown to be soluble, and was released from lymphocytes after a rapid, immunologically specific interaction with the sensitising antigen.
Lymphocytes cytotoxic for mouse embryo fibroblasts (MEF) infected with murine cytomegalovirus (MCMV) were produced by in vitro culture of "memory" spleen cells with UV-irradiated, MCMV-infected, MEF. Cytotoxic lymphocytes were developed from spleen cells of mice 10 to 240 days after infection with MCMV. The cytotoxic cells carried the theta and Ly 2 antigens, and were H-2 restricted in the recognition of infected target cells.
Intact quokkas (Setonix brachyurus) were grafted with thymus and skin as neonates. Fifty seven percent of primary thymus grafts persisted when donors were less than 32 days of age, compared with only 20% when the dornors were juveniles. This suggested that neonatal tissue was more readily accepted than tissue from adult animals. When the recipients had left the pouch, induced tolerance was tested by grafting thymus and skin from the original donors. Second thymus grafts were generally unsuccessful; however, second skin grafts were accepted and remained intact over the three-year period of observation, provided that the hosts were less than about 40 days of age at the time the first graft were placed.
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Human peripheral blood mononuclear cells which mediate antibody-dependent cellular cytotoxicity (ADCC) against herpes simplex virus- (HSV) infected target cells consist of both adherent (MA) and nonadherent (MNA) effector cell populations. These two cell populations can be distinguished by their different phagocytic properties and morphologic appearance, their requirement for antibody in the ADCC reaction, and the rapidity with which they lyse target cells in the presence of immune serum. The MA cells are predominantly phagocytic and have the morphologic characteristics of monocyte-macrophages, whereas the MNA cells are nonphagocytic and appear to be small to medium-sized lymphocytes. Optimal expression of ADCC by MA cells requires higher concentrations of immune serum than does MNA cell-mediated ADCC. MA-mediated cell killing is first detectable by 8 hr and reaches completion after 24 hr of incubation. In contrast, MNA-mediated ADCC produces target cell damage by 2 hr and reaches completion at 8 hr of incubation. Unlike MNA effector cells, the MA effector cells are profoundly inhibited after preincubation with either latex or silica particles. The HSV immune status of the donor had no effect on the ability of either cell population to mediate ADCC. These data demonstrate the participation of both nonadherent mononuclear cells, presumably K cells, and monocyte-macrophages, in ADCC directed against HSV-infected target cells.