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R B Markham

Publications and source records attributed to R B Markham.

44 records · Page 3Linked to original sources

Selective sensitivity to hydrocortisone of regulatory functions that determine the magnitude of the antibody response to type III pneumococcal polysaccharide.

Previous studies on the basis for the immunosuppressive potential of adrenal corticosteroids have stressed that the effects of these agents on immune functions depend on the animal species being considered, as well as the subpopulations of lymphocytes involved in the expression of immune functions examined. In the present work, we have evaluated the effect of a single dose of hydrocortisone on three different immunoregulatory functions that can influence the magnitude of an antibody response to Type III pneumococcal polysaccharide (SSS-III) in mice; these functions include suppressor, amplifier, and helper activity that are dependent upon the presence of distinct subpopulations of thymus-derived (T) cells. The results obtained show that a single injection of a relatively large dose of hydrocortisone, when given at the time of priming with carrier, eliminated all evidence of carrier-specific helper T cell activity; hydrocortisone was also found to eliminate a significant amount of helper T cell activity when given after such activity had been generated. But, under the same experimental conditions, suppressor and amplifier T cell activities were unaffected, even in this steroid-sensitive species. Such selective sensitivity may account for some of the immunosuppressive potency of steroids.

Animals↗

Early idiopathic hemochromatosis with absent stainable bone marrow iron stores.

Early idiopathic hemochromatosis was diagnosed in a 52-year-old woman during the course of a hospitalization for another disorder. Quantitative studies revealed massive hepatic parenchymal siderosis and absent stainable marrow iron. Additionally, intestinal absorption and hepatic sequestration of radiolabeled iron were elevated. These studies in a patient with very early hemochromatosis, before organ damage, complement observations previously made in patients with advanced disease and provide further support for the concept that this disorder may result from impaired reticuloendothelial handling of iron.

Bloodletting↗

Effect of concanavalin A on lymphocyte interactions involved in the antibody response to type III pneumococcal polysaccharide I. Comparison of the suppression induced by con A and low dose paralysis.

Concanavalin A (Con A) administered at the time of immunization induces suppression of the in vivo splenic plaque-forming cell (PFC) response to type III pneumococcal polysaccharide (SSS-III). As with low dose paralysis of the PFC response to SSS-III, Con A-induced suppression could not be demonstrated in congenitally athymic (nu/nu) mice and could be eliminated partially by treatment with anti-lymphocyte serum (ALS). The kinetics for Con A-induced suppression paralleled those for low dose paralysis of the antibody response to SSS-III. These findings support the view that Con A-induced suppression is produced in vivo by suppressor T cells and that this form of suppression shares with low dose paralysis a common pathway through which suppression is mediated.

Animals↗

Sensitivity of amplifier T cells involved in the antibody response to type III pneumococcal polysaccharide to anti-lymphocyte serum.

Amplifier T cells responsible for enhancement of the antibody response to type III pneumococcal polysaccharide have been shown to be resistant to the effects of antilymphocyte serum (ALS) given at the time of immunization, a treatment that eliminates suppressor T cell activity. The resistance of amplifier T cells to ALS can be attributed to the fact that their activity develops after that of suppressor T cells. ALS given 1 or 2 days after immunization does abrogate amplifier T cell activity, independent of the mode by which that activity is elicited. The data emphasize the importance of kinetic considerations in understanding the effects produced by immunologically active agents such as ALS.

Animals↗

Effect of concanavalin A on lymphocyte interactions involved in the antibody response to type III pneumococcal polysaccharide. II. Ability of suppressor T cells to act on both B cells and amplified T cells to limit the magnitude of the antibody response.

When administered 2 days after immunization with 0.5 microgram Type III pneumococcal polysaccharide (SSS-III), the T lymphocyte mitogen concanavalin A (Con A) stimulates a 2.6-to 7-fold enhancement of the plaque-forming cells (PFC) response to SSS-III in vivo. This enhancement requires the presence of amplified T cells, which act by driving PFC or their precursors to extra rounds of proliferation. The extra proliferation that can be stimulated by Con A is not seen in the normal primary response to SSS-III; but treatment with anti-lymphocyte serum (ALS) to remove suppressor T cells will permit the additional proliferation to occur. This indicates that in the primary response to SSS-III, suppressor T cells act on amplifier T cells to limit the magnitude of the antibody response. Only suppression of B cells can account for the further suppression induced by Con A given at the time of immunization or by low-dose paralysis of the SSS-III response. The relatively late development of amplified activity compared to suppressor activity appears to account for the absence of amplifier activity after primary immunization with SSS-III. It is apparent that one can explain the regulatory effects observed during the development of an immune response to SSS-III only by considering both T cell- B cell and T cell- T cell interactions, together with the temporal relationships involved in those interactions.

Animals↗

Selective immunosuppressive activity of steroids in mice inoculated with the Moloney Sarcoma virus (38503).

A steroid, 6-chloro-17-hydroxypregna-1,4,6-triene-3,20-doine (CHP) that exhibits selective activity in several models of cellular immunity including an apparent inhibitory action on the elicitation of delayed hypersensitivity, was examined in a new, simple experimental model for assessing aspects of host-cell-mediated immunological competence. This model is based upon the capacity of the adult mouse to prevent the progressive growth of tumors induced by the Moloney sarcoma virus. Two steroids reported to have immunosuppressive activity in other assay systems, namely, cortisol and progesterone, were also studied. Control mice and those injected with CHP maintained their capacity to reject the tumor. In contrast, significant numbers of mice receiving a single large injection of cortisol or progesterone succumbed to progressive tumor growth under the experimental conditions used. The data indicate that CHP, while influencing selected parameters of cellular immunity, e.g., the elicitation of delayed hypersensitivity, does not decrease the capacity of the host to mount a defense against the progressive growth of the Moloney virus-induced sarcoma. The results indicate that CHP may be useful in modulating specific aspects of cellular immunity without altering others. In addition, the experimental model described provides a simple method of assessing the possible immunosuppressive effects of naturally occurring and synthetic agents on viral-induced tumor growth.

Animals↗

Seal finger.

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Adult↗

Immunologic basis for mouse protection provided by high-molecular-weight polysaccharide from immunotype 1 Pseudomonas aeruginosa.

Antibody responses were assayed in inbred strains of mice immunized with a high-molecular-weight polysaccharide (IT-1 PS) isolated from Fisher immunotype 1 Pseudomonas aeruginosa (P. aeruginosa 1). C3H/ANF mice generated the greatest antibody response after immunization with 1 microgram of antigen and could then survive challenge with 5 LD100 of P. aeruginosa 1 organisms. BALB/c mice produced lower levels of antibody and did so only after immunization with 50 micrograms of IT-1 PS. These mice could only withstand challenge with 1 LD100 of P. aeruginosa 1. The specificity of the antibody produced by these two strains differed. Antibody produced in C3H/ANF mice after primary immunization with either 1 microgram or 50 micrograms of IT-1 PS did not cross-react with other immunotypes of P. aeruginosa. Antibody produced in BALB/c mice after a primary immunization with 50 micrograms of IT-1 PS cross-reacted with polysaccharide isolated from Fisher immunotype 2 P. aeruginosa. These data indicate that, even within the same species, antibody responses to immunization with P. aeruginosa IT-1 PS may be qualitatively different. This kind of variation in immune response patterns will have to be considered in developing optimal regimens for immunization in human vaccine trials.

Animals↗