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Biomedical subjects

T E Miller

Publications and source records attributed to T E Miller.

At least 145 records · Page 8Linked to original sources
PubMed1974

Potentiation of T-cell-mediated immunity by selective suppression of antibody formation with cyclophosphamide.

Delayed-type hypersensitivity (DTH) appears in mice immunized with less than an optimal immunogenic dose of sheep red blood cells (SRBC), but is blocked progressively as antibody production increases in response to larger doses of SRBC. Treatment with cyclophosphamide (CY) was shown to release T cells from this inhibitory influence of the humoral response, and cause enhancement of DTH. The magnitude of this enhancing effect on T-cell activity was markedly dependent on the time of treatment relative to the time of immunization, and on the time chosen for measuring DTH. The reasons for these pronounced effects of timing are threefold: (a) CY given before antigenic stimulation has a long-lasting effect on antibody formation, but no apparent effect on the precursors of activated T cells. (b) After antigenic stimulation, T cells also become susceptible to CY. (c) The production of a nonspecific participant (monocyte) in the DTH reaction is also suppressed by CY, though the supply of circulating monocytes is not immediately affected by the drug. The differential effect of CY on T and B lymphocytes depends on the differing physiological states of the majority of cells that make up these two populations. The former are resting cells that are insensitive to CY until exposed to specific antigen, while the latter are drawn from a rapidly replicating precursor pool and are susceptible to CY at all times.

Animals↗
PubMed1974

Influence of dose and route of antigen injection on the immunological induction of T cells.

Delayed-type hypersensitivity (DTH) develops in the absence of an adjuvant when mice are injected intravenously or subcutaneously with an appropriate dose of sheep red blood cells (SRBC). The optimal intravenous dose of 10(5) SRBC (in CD-1 mice) produces maximum DTH which decays exponentially from its peak on day 4. Increasing the dose of SRBC reduces and eventually abolishes all evidence of DTH. DTH fails to reappear in respose to secondary stimulation except in splenectomized mice in whom the development of DTH is not suppressed, even by massive doses of SRBC. Hence the suppression cannot be due to antigen as such. The optimal dose of SRBC for sensitization by footpad inoculation is 100-fold higher (10(7) SRBC in CD-1 mice), but even 10(9) SRBC do not block the induction of DTH by this route of immunization. A blocking dose of SRBC, given intravenously 1 day before footpad inoculation, completely suppresses cell proliferation in the draining lymph node, prevents PFC production there, and blocks the induction of DTH by a sensitizing dose of SRBC. If given 1 day after footpad sensitization, intravenous antigen has little effect on the cellular response in the regional node but DTH is still completely suppressed. Blocking of induction and expression may depend, therefore, on different mechanisms.

Animals↗
PubMed1974

Feedback inhibition of specifically sensitized lymphocytes.

An explanation was sought for the fact that delayed-type hypersensitivity (DTH) does not normally occur in response to T-cell-dependent antigens unless an adjuvant is used. But when sheep red blood cells (SRBC) were administered intravenously DTH did appear, provided that the dose of antigen was less than that required to give a maximum antibody response. Animals in which T-cell activity had been blocked by a large dose of antigen could not be sensitized adoptively, and their spleen cells failed to transfer DTH to normal recipients. The serum of blocked animals partially inhibited the induction of DTH, and after absorption with SRBC its blocking activity increased substantially. Moreover, absorbed serum inhibited DTH in previously sensitized animals, but it did not inhibit the proliferative response to SRBC in peripheral lymph nodes or reduce the number of plaque-forming cells produced therein. On the contrary, the hemagglutinating titer was actually increased by blocking serum even though DTH was totally suppressed. It is concluded that a product of the interaction between antigens and antibody blocks the activated T cells which mediate DTH without interfering with helper cells.

Animals↗
PubMed1971

Metabolic event involved in the bactericidal activity of normal mouse macrophages.

The intracellular bactericidal activity of normal mouse peritoneal macrophages requires a viable, actively metabolizing cell. The killing mechanism is apparently dependent upon an intact respiratory electron chain since inhibition of activity is achieved by anaerobiosis, cyanide, antimycin A, or amytal. By way of contrast, inhibitors of oxidative phosphorylation, glycolysis, the Krebs citric acid cycle, and the phosphogluconate oxidative pathway are without influence on this antibacterial activity. Various dyes and electron acceptors with selected reduction-oxidation values also inhibit killing. Although the bactericidal substance was not identified, the data are consistent with the hypothesis that the primary agent is hydrogen peroxide.

Journal Article↗
PubMed1969

Killing and lysis of gram-negative bacteria through the synergistic effect of hydrogen peroxide, ascorbic acid, and lysozyme.

A mixture of hydrogen peroxide and ascorbic acid has been found to generate an antibacterial mechanism which is active against gram-negative bacteria. It results in bacterial death and renders the organism sensitive to lysis by lysozyme. Under the conditions used, horseradish peroxidase did not augment the antibacterial effect. It is suggested that the effector mechanism involves the generation of short-lived free radicals which disturb the integrity of the cell wall. This effect alone might kill bacteria by interfering with selective permeability, but in the presence of lysozyme a further bactericidal activity is accomplished by complete disruption of the cell. It is proposed that a transient antibacterial system such as that described could exist within phagocytic cells. Free radicals would be formed through the interaction of certain oxidizable substances and hydrogen peroxide, which is produced during the enhanced metabolic activity that accompanies ingestion of bacteria. Such a system would help to explain why macrophages, which are apparently devoid of preformed bactericidins, are nonetheless very efficient in killing most phagocytosed bacteria.

Ascorbic Acid↗
PubMed1969

Local immune response in experimental pyelonephritis.

Experiments using an in vitro method of assessing protein synthesis by (14)C amino acid incorporation were designed to determine whether pyelonephritic kidneys were capable of local antibody production. Unilateral pyelonephritis was produced in rabbits by intravenous injection of E. coli 0-75 while one ureter was transiently occluded. The capability of protein and immunoglobulin synthesis by pyelonephritic kidneys, contralateral kidneys, normal kidneys, and spleens from normal and pyelonephritic animals was measured. Enhanced protein and immunoglobulin syntheses by pyelonephritic kidneys were first detected by the 11th day after infection and persisted through day 120. In individual experiments the pyelonephritic kidney produced 6-170 times more soluble protein than did the contralateral, uninfected kidney. In seven experiments, IgG comprised a mean of 72% of the total protein synthesized by the pyelonephritic kidney, compared with a mean of 19% in the contralateral kidney. IgA accounted for 10 and 9%, respectively. In these experiments 0.6-17% of the synthesized IgG was precipitable by somatic antigen of the E. coli 0-75. The capability of the pyelonephritic kidney to synthesize soluble protein was quantitatively similar to that of spleens from infected animals. The proportion of synthesized protein which was immunoglobulin G, however, was greater in the pyelonephritic kidney than in the spleen. Furthermore, specific antibody synthesis by the pyelonephritic kidney persisted longer than did synthesis by the spleen of the same animal. These studies provide evidence that in experimental pyelonephritis a significant local immune response occurs which is represented primarily by the production of IgG. Local immunoglobulin formation and specific antibody synthesis may be important factors in determining patterns of host resistance.

Amino Acids↗