Biomedical subjects

C M Flory

Publications and source records attributed to C M Flory.

28 records · Page 2Linked to original sources

PubMed1992

Effects of in vivo T lymphocyte subset depletion on mycobacterial infections in mice.

The relative importance of CD4+ and CD8+ T cell subsets in the expression of acquired resistance to systemic infection by Mycobacterium kansasii was determined. T cell subsets were depleted in thymectomized C57BL/6 mice by the intravenous administration of monoclonal antibodies directed against the relevant T cell determinants. Depletion of the CD4+ subset exacerbated the severity of the infection in intravenously challenged mice. This effect was apparent in the first 2 weeks of the infection and persisted throughout the 12 weeks of the study. On the other hand, depletion of the CD8+ cells had no apparent effect on the growth curves. Infections by Mycobacterium tuberculosis Erdman or bacille Calmette-Guérin (BCG) Pasteur were also substantially enhanced by CD4 depletion, but not by the depletion of CD8+ cells. The effect of subset depletion on infections by M. tuberculosis and BCG was examined in both innately susceptible C57BL/6 mice and innately resistant B6D2 mice.

Animals↗

PubMed1992

Immunization of mice with the antigen A60 of Mycobacterium bovis BCG.

Antigen 60 (A60) is a thermostable component of the cytoplasm of Mycobacterium tuberculosis and BCG which can be fractionated into at least 15 protein bands when analysed by Western blot. Normal B6D2 mice were immunized subcutaneously with 20 micrograms of the A60 protein suspended in Freund's incomplete adjuvant (FIA) or in saline. Three weeks later the mice received a second dose of vaccine followed 2 weeks later by an aerogenic challenge with approximately 10(3) CFU of M. tuberculosis Erdman. The mice receiving the adjuvanted A60 showed a significant reduction (P less than 0.05) in the number of viable organisms recovered from the lungs and the spleen 3 weeks after challenge. However, this response was less than that seen in BCG vaccinated controls.

Animals↗

PubMed1992

Immunization of mice with mycobacterial culture filtrate proteins.

Culture filtrate proteins were obtained from Mycobacterium tuberculosis cultures after 7 days growth in Proskauer and Beck medium. The protein yield increased substantially to peak about the time the number of viable organisms reached its maximum level (day 8). Examination of the protein concentrate by SDS-PAGE revealed the presence of at least 12 separate protein bands varying from 10 to 90 kD. Mice were injected subcutaneously with 20 micrograms of M. tuberculosis culture filtrate (MTCF) protein suspended in saline or Freund's complete or incomplete adjuvant. The vaccinated mice were subjected to an aerogenic challenge with 10(3) colony-forming unit (CFU) M. tuberculosis Erdman and a significant reduction in the number of viable organisms was observed in the spleens and lungs determined over a 21-day period compared with age-matched normal controls. Mice immunized with the same culture filtrate proteins bound to nitrocellulose particles also showed some resistance to the virulent challenge, suggesting that individual antigens present in the culture filtrate were able to induce a protective T cell-mediated immune response in appropriately immunized mice.

Animals↗

PubMed1992

T-cell immune responses in Mycobacterium avium-infected mice.

Mycobacterium avium infection was substantially more severe in C57BL/6 (Bcgs) than in (C57BL/6 x DBA/2)F1 hybrid (Bcgr) mice both in terms of bacterial growth in the spleens and lungs and in host survival. Prior Mycobacterium bovis BCG vaccination resulted in increased resistance as well as enhanced tuberculin hypersensitivity to both PPD-S (Mycobacterium tuberculosis) and PPD-A (M. avium). Mice heavily infected with M. avium were used as T-cell donors in an adoptive transfer system. Substantial resistance was observed for both recipient hosts regardless of the genotype of the donor strain. Transfer of resistance was ablated by treatment of the immune spleen cells with anti-Thy 1.2 monoclonal antibody and complement or by cyclophosphamide treatment. Spleen cells which were monodepleted of L3T4+ or Lyt-2+ T cells did not lose their ability to transfer resistance against a subsequent challenge. However, when these cells were doubly deleted, all resistance was ablated in both the BCG-susceptible and -resistant mice. The recipient host expressed a detectable adoptive immune response although the donor had been unable to reduce the growth of the primary M. avium infection in vivo.

Analysis of Variance↗

PubMed1991

The influence of adrenergic and cholinergic agents on the chemiluminescent and mitogenic responses of leukocytes from the rainbow trout, Oncorhynchus mykiss.

In a previous report, it was shown that agonists of cholinergic or alpha-adrenergic receptors enhance, whereas beta-adrenergic agonists suppress, in vitro antibody responses by splenic leukocytes from rainbow trout. The present study addresses the mechanisms by which autonomic neurotransmitters (or their analogs) could affect this antibody response. Possibilities include an influence on accessory cell function, on the clonal proliferation of antigen-stimulated lymphocytes, and/or on the synthesis and secretion of antibody. Epinephrine and selective beta-adrenergic agonists suppressed whereas both alpha and cholinergic receptor agonists enhanced the ability of stimulated pronephric leukocytes (mainly macrophages and neutrophils) to produce reactive oxygen species, suggesting that accessory cells may be a target of these agents in the antibody response. Beta-adrenergic agonists also suppressed the proliferative response of splenic leukocytes to LPS, Con A, and PHA. There was no effect, however, of alpha-adrenergic or cholinergic-receptor agonists on mitogenic responses.

Animals↗

PubMed1991

Memory T cell-mediated resistance to Mycobacterium tuberculosis infection in innately susceptible and resistant mice.

The memory T cell immune response to Mycobacterium tuberculosis infection was examined in strains of mice which vary in their natural susceptibility to Mycobacterium bovis BCG infection. Naturally susceptible (NS) C57BL/6 and naturally resistant (NR) B6D2 F1 hybrid mice were infected with a sublethal dose of M. tuberculosis and then given antibiotic therapy beginning 2 weeks postinfection. T cells from both strains of mice transferred significant levels of resistance to syngeneic mice challenged aerogenically with M. tuberculosis. This memory response was not substantially reduced by depletion of either L3T4+ or Lyt2+ T cells from the donor mice but was ablated by depletion of both T cell subsets. Cyclophosphamide pretreatment of C57BL/6 memory T cell donors also ablated the resistance transferred to recipient mice. In contrast, B6D2 memory T cells were not affected by cyclophosphamide treatment, suggesting that differences may exist in the metabolic state of the memory T cells in the two donor strains, despite the fact that they both develop similar levels of acquired resistance to a subsequent tuberculous challenge.

Animals↗

PubMed1991

The Independent Living Program: an alternative to institutionalization.

The Independent Living Program is a joint venture demonstration project in Ardmore, Pennsylvania. Partners are Community Health Affiliates, a one-hundred-plus-year-old visiting nurse association and integrated home care agency, and neighboring Ardmore House, a 63-unit residential facility for a well-elderly population with extremely limited financial means.

Activities of Daily Living↗

PubMed1990

Phylogeny of neuroimmunoregulation: effects of adrenergic and cholinergic agents on the in vitro antibody response of the rainbow trout, Onchorynchus mykiss.

The ability of the nervous system to influence a variety of immune processes has been well established in mammals. There are, however, few studies on how the peripheral nervous system might affect immunity in the lower vertebrates. This study demonstrates that autonomic neurotransmitters (or their analogs) can significantly influence the in vitro induction of antibody-secreting cells in cultures of splenic leukocytes from the rainbow trout. Beta-adrenergic agonists suppress, while alpha-2 adrenergic and cholinergic agonists enhance the in vitro antibody response to the T-independent antigen TNP-LPS. These effects are receptor mediated as evidenced by the action of specific receptor antagonists. These results, taken with the previous findings that the salmonid spleen contains a rich adrenergic innervation, and that chemical sympathectomy results in an enhanced in vivo antibody response, strongly suggest that autonomic neurotransmitters may affect immune function in teleosts via leukocyte receptors for these factors.

Animals↗

PubMed1989

Leukocytes of rainbow trout (Oncorhynchus mykiss) pronephros: cell types producing superoxide anion.

Fish pronephric and blood leukocytes yield a chemiluminescent response (CL) when stimulated appropriately. This response reflects the production of highly reactive oxygen derivatives which contribute to oxygen-dependent killing of targets such as pathogens and parasites. From suspensions of pronephric cells of the Rainbow trout, Oncorhynchus mykiss, we have obtained populations enriched for CL-positive cells. Four bands of cells were obtained using continuous gradients generated with 60% Percoll. The leukocytes of band II showed a very strong PMA-induced CL response, the magnitude of which was several times higher than that observed with equivalent numbers of cells form unseparated pronephric cell suspensions. Cells present in other bands were not significantly chemiluminescent. Flow cytometric analysis showed that band II contained large granular cells and small granular cells. Cytochemical analysis showed that this subpopulation was greatly enriched with neutrophils. Many band II cells adhere to glass whereas few band III cells do so. The glass-adherent cells loose their CL potential after a few days in vitro, whereas the nonadherent cells retain their CL responsiveness for at least a week in vitro.

Animals↗

PubMed1989

Autonomic innervation of the spleen of the coho salmon, Oncorhynchus kisutch. a histochemical demonstration and preliminary assessment of its immunoregulatory role.

Regulation of immunity by the nervous system, now a well-established phenomenon in mammals, is effected in part through the autonomic innervation of lymphoid tissues. Noradrenergic fibers specifically target lymphocyte-rich areas in mammalian lymphoid tissues, and their ablation, or the administration of adrenergic agents, can significantly alter immune responses. This study demonstrates that the spleen of the coho salmon is also richly innervated by adrenergic neurons. While this innervation enters the spleen and remains largely associated with the splenic vasculature, fibers can also be observed entering the parenchyma. Although the coho spleen does not possess a well-developed white pulp, aggregations of leukocytes are found adjacent to the major blood vessels in close proximity to the vascular nervous tissue and parenchymal fibers. Chemical sympathectomy with 6-hydroxydopamine results in a significant enhancement of the splenic antibody-secreting cell response to trinitrophenylated sheep red blood cells. These results suggest that sympathectomy is removing a constraint, in the form of inhibitory catecholamines, on the immune response. The potential benefits from a teleost model of neural-immune interactions are discussed.

Adrenergic Fibers↗