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Biomedical subjects

A C Allison

Publications and source records attributed to A C Allison.

At least 181 records · Page 10Linked to original sources
PubMed1977

Dengue viruses and mononuclear phagocytes. II. Identity of blood and tissue leukocytes supporting in vitro infection.

Studies were made on the identity of human and monkey mononuclear leukocytes permissive to antibody-enhanced dengue 2 virus (D2V) infection. In cultures of peripheral blood leukocytes (PBL) inoculated immediately after separation, it was concluded that only mononuclear phagocytes support dengue infection. This is based upon observations that D2V-permissive cells were resistant to 1,200 rads, were both plastic adherent and nonadherent, were removed when passed through nylon wool columns in 10 percent fetal bovine serum or 100 percent autologous serum, and were destroyed by incubation with 100 mug/ml particulate silica. On direct immunofluorescence staining, perinuclear dengue antigen was visualized at 24 h, becoming maximal at 60 h. Antigen-containing cells had ample cytoplasm, ruffled cytoplasmic membrane, and 73 percent were actively phagocytic. As further evidence of the infection of mononuclear phagocytes, antibody-enhanced D2V replication was observed in bone marrow cultures from five of five rhesus monkeys, but not in cell cultures of spleen, thymus, or lymph nodes prepared from the same animals. It is hypothesized that dengue virus complexed with non-neutralizing antibody is internalized by immune phagocytosis in a mononuclear phagocyte with a defective virus-destroying mechanism. Dengue permissiveness may depend upon cellular immaturity since bone marrow leukocytes could be infected even when held for 4 days before infection while PBL held for this time decreased in permissiveness. In vitro antibody-dependent infection of mononuclear phagocytes should prove useful as a model for study of immunopathologic mechanisms in human dengue.

Animals↗
PubMed1977

The role of de novo purine synthesis in lymphocyte transformation.

Genetic defects in purine metabolism are associated with severe immunodeficiency. Adenosine deaminase deficiency impairs the function of both B- and T-lymphocytes whereas in purine nucleoside (inosine) phosphorylase deficiency there is more severe impairment of T-lymphocyte functions than of B-lymphocyte functions. The relative unimportance of the salvage pathway catalysed by hypoxanthine-guanine phosphoribosyltransferase is shown by the normal responses of T-lymphocytes from patients with the Lesch-Nyhan syndrome to antigenic and mitogenic stimulation. A mild deficiency of B-lymphocyte function is found in these patients. Agents inhibiting the de novo pathway of purine synthesis, including azaserine, 6-mercaptopurine and azathioprine in low doses, block the responses of normal human lymphocytes to mitogenic stimulation. These observations emphasize the importance of the de novo pathway of purine synthesis in lymphocyte responses to antigenic and mitogenic stimulation. There is considerable heterogeneity in the amount of labelled uridine incorporated into human and rat lymphocytes. This does not appear to reflect only a difference between T- and B-lymphocytes

Adenine Phosphoribosyltransferase↗
PubMed1977

Purine metabolism and control of cell proliferation.

Exposure of normal lymphocytes to phytohaemagglutinin or other lectin mitogens results in increased concentrations of 5-phosphoribosyl-1-pyrophosphate (PP-ribose-P) within minutes. Subsequently, synthesis of purine nucleotides by both the de novo and the salvage pathways is facilitated. This change is prevented by proliferation-inhibiting concentrations of exogenous adenosine. The capacity of lymphocytes to metabolize both adenine and adenosine is increased several-fold by incubation with phytohaemagglutinin but the specific activities of the respective first-step enzymes are not significantly altered. These results suggest that the relatively low quantity of PP-ribose-P available in normal lymphocytes is a major factor limiting the synthesis of purine nucleotides and may be important for the maintenance of the quiescent state. Increased availability of PP-ribose-P may also be associated with proliferative activation of fibroblast-like cells: chick embryo fibroblast cultures released from density-dependent inhibition of growth by insulin, trypsin or serum rapidly increase the rate of adenine incorporation into nucleotides. Chick embryo fibroblasts transformed by Rous sarcoma virus, but not cells infected with the respective non-transforming leukosis virus, show PP-ribose-P concentrations higher than those observed in normal cells.

Adenine↗
PubMed1977

Cell membranes in cytotoxicity.

Silica particles are cytotoxic for macrophages because they damage the membranes around secondary lysosomes in which the particles are engulfed. Hydroxyl groups of silicic acid on the surface of the particles form hydrogen bonds with phosphate ester groups of phospholipids and disrupt a variety of natural and artificial membranes. Asbestos fibers induce secretion of hydrolytic enzymes from cultured macrophages. Magnesium hydroxide groups of chrysotile asbestos interact ionically with ionized sialic acid residues of membrane glycoproteins, increase passive cation flux and produce osmotic lysis. The terminal components of complement (C5b-C9) when inserted into the bilayer structure also increase passive cation flux and produce osmotic lysis. The small complement cleavage product C3a is lytic for several cell types, especially malignant cells. The mechanism by which specifically sensitized thymus-derived (T)-lymphocytes kill tumour cells is discussed. Plasma membranes from effector lymphocytes possess considerable cytolytic potential, which is dependent on the activity of a membrane-associated proteinase.

Animals↗
PubMed1977

Cryopreservation of mouse peritoneal macrophages.

A method for the preservation of mouse peritoneal macrophages is described. Using 5% dimethylsulphoxide with either a cooling rate of 1 degree C/min or two-step cooling with 10 min interruption at -30 degrres C allows 80% survival as judged by pinocytic activity. An important finding was that the cells must be handled at 0 degrees C both before and after freezing.

Animals↗
PubMed1977

Protection of mice against Babesia spp. and Plasmodium spp. with killed Corynebacterium parvum.

Mice which had been pre-treated with killed Corynebacterium parvum given intravenously or intraperitoneally, but not subcutaneously, were completely resistant to infection with Babesia microti or B. rodhaini, and were protected from death caused by Plasmodium vinckei or P. chabaudi infection. There is evidence that the parasites died within circulating erythrocytes. This occurred much too soon for a specific antibody response to be evoked, and no antibody could be detected by the indirect fluorescent-antibody technique. Thus it is suggested that a non-specific soluble mediator may play an important role in the protection observed.

Animals↗
PubMed1977

Intra-erythrocytic death of the parasite in mice recovering from infection with Babesia microti.

As mice recover from infection with Babesia microti, abnormal forms of the parasite are present in some red cells. These forms are non-infective, indistinguishable by light microscopy from those present after treatment with amicarbalide, a babesicidal drug, and persist in splenectomized mice. Electron microscopy confirmed that these abnormal forms are degenerating intra-erythrocytic parasites. In the absence of evidence for death of B. microti elsewhere in the body, it appears that infections of mice with this parasite are normally terminated by their death within circulating red cells. This has important implications for the mechanism of immunity to both this parasite and those Plasmodium spp. with which it cross-protects in this host.

Animals↗
PubMed1977

Production by mixed lymphocyte cultures of a type II interferon able to protect macrophages against virus infection.

In supernatants of mixed mouse spleen cell cultures established for 4 days, a species-specific inhibitor of virus replication with a broad antiviral spectrum was found. The inhibitor was destroyed by trypsin, was nondialyzable and acid labile, and was not neutralized by antibody to mouse L cell interferon. This indicates that in mixed lymphocyte cultures a type II interferon is made that has no immunological relationship with "fibroblast" interferon. This leukocyte product was shown to protect mouse hepatitis viruses. It is suggested that lymphocyte interferon may collaborate with macrophages in host defense against viruses, as a mediator of cellular immunity.

Animals↗
PubMed1977

Suppression of babesiosis in BCG-infected mice and its correlation with tumor inhibition.

Infection of mice with Bacillus Calmette-Guérin (BCG) provided good protection against Babesia species. The intensity and duration of this protection was similar to that established after natural recovery from babesiosis. It developed too soon after the first exposure to the parasite, and was too radioresistant, to be attributable to specific antibody production. In addition, the parasites degenerated within circulating erythrocytes. This phenomenon is inconsistent with phagocytosis or lysis of parasites or parasitized cells, or prevention of entry of parasites into erythrocytes, causing the observed protection. Hence the phenomenon is best explained by the release of a nonspecific mediator that can limit multiplication of parasites within erythrocytes. These results not only throw light on mechanisms of immunity against hemoprotozoa. There are many points of similarity between the nonspecific protection BCG and Corynebactium parvum provide against Babesia species and inhibition of tumor growth by these agents. Therefore, babesiosis in mice may be a convenient experimental model for assessing stimulation of the mononuclear phagocyte system, which appears to be the basis of nonspecific immunity against bacteria, parasites, and tumors.

Animals↗
PubMed1977

Role of T lymphocytes in recovery from murine cytomegalovirus infection.

Congenitally athymic nude (Nu/Nu) mice inoculated intraperitoneally with murine cytomegalovirus (MCMV), in doses as low as 1.3 X 10(1) plaque-forming units succumbed to the infection. In contrast, the mean lethal dose for heteroxygous euthymic (Nu/+) littermates was 4 X 10(3) plaque-forming units. Though histopathological changes consistent with MCMV infection were found in the spleen, lungs, and adrenals of nude mice, there were only small focal areas of involvement in the liver. In contrast, Nu/+ mice dying from infection had pathological evidence of severe hepatitis. Spleen cells from immune and control BALB/c mice were injected intravenously into syngeneic mice that had been inoculated previously with lethal doses of MCMV intraperitoneally. Mice receiving 1 X 10(7) or more immune spleen cells were protected against the infection, whereas mice receiving 1 X 10(8) control spleen cells or immune serum were not. Treatment of immune spleen cells with anti-theta serum and complement significantly reduced their protective effect. Immune mechanisms associated with T lymphocytes appear to be critical for recovery from MCMV infection.

Animals↗
PubMed1977

Immunosuppressive effects of lymphocyte (type II) and leucocyte (type I) interferon on primary antibody responses in vivo and in vitro.

We have tested the hypothesis that type II interferon (IF), released by immune lymphocytes after in vivo stimulation with tuberculin, has immunosuppressive effects. Mycobacterium bovis (BCG) infected mice injected with tuberculin showed a very intense suppression of antibody response to sheep erythrocytes. Sera containing lymphocyte IF strongly inhibited primary immune responses to sheep erythrocytes in cultures. Addition of macrophages could not counteract the in vitro immunosuppressive effects of lymphocyte IF, suggesting that the main effect is exerted directly on lymphocytes. Sendai virus-induced leucocyte (type I) IF was also shown to have suppressive effects in vivo and in vitro. However, lymphocyte IF was shown to be much more immunosuppressive than a preparation of type I interferon with equivalent antiviral potency. Thus type II IF, as a product of activated lymphocytes, may have a major immunoregulatory role.

Animals↗
PubMed1977

Identification of human mononuclear leucocyte populations by esterase staining.

Histochemical staining for alpha-naphthyl (non-specific) esterase has been employed to define subpopulations of human peripheral blood lymphocytes and monocytes. To define optimal conditions for staining, various fixatives, incubation times and cell preparations were compared. The great majority of human blood lymphocytes were found to have discrete granules of reaction product. More than 80% of T lymphocytes separated by E rosetting are esterase-positive whereas non-T lymphocytes are esterase-negative. Lymphocytes transformed by polyclonal mitogens lose their esterase-staining granules, which suggests that immature T cells are esterase-negative. Most blood monocytes show a diffuse cytoplasmic esterase reaction product and are phagocytic. However, about 20% of diffusely stained cells are not phagocytic. When leucocytes are cultured for 24 to 48 hr, the total number of esterase-positive cells increases and the great majority are phagocytic. This is interpreted as maturation of precursors into mature esterase-positive phagocytic monocytes. When cultured for longer periods, some lose phagocytic capacity and acquire the characteristics of secretory cells. Esterase-staining of lymph node sections allowed the identification of T- and B-dependent areas as well as macrophages related to sinuses. The esterase-staining technique could play a useful role in clinical and experimental immunology.

Esterases↗
PubMed1977

Complement activation by the alternative pathway and macrophage enzyme secretion in the pathogenesis of chronic inflammation.

A number of stimuli known to induce acid hydrolase secretion from cultured macrophages were examined for their ability to activate C3 via the alternative pathway of the complement system. Loss of haemolytically active C3 was checked in normal and C4-deficient guinea-pig serum. For comparison the interactions of cultured macrophages with other agents well known as potent activators of the alternative pathway of the complement system have been investigated. As judged by their activity in these assays, group A streptococcal cell walls, different carrageenan preparations, dental plaque and Actinomyces viscosus were all capable of initiating the alternative pathway but differed with respect to their potency and their ability to inhibit C3 turnover at high concentrations. Zymosan, some carrageenans, polyanethol sulphonate, and Corynebacterium parvum all induce the release of hydrolytic enzymes from macrophages in culture, even in the absence of serum in the medium. The release is time- and dose-dependent and is not associated with loss of the cytoplasmic enzyme lactate dehydrogenase or any other sign of cell death. The parallelism between the capacity of several agents to activate the complement system via the alternative pathway and to induce inflammatory responses in vivo and selective lysosoma enzyme secretion from cultures of macrophages is discussed.

Animals↗