Biomedical subjects
Publications and source records attributed to N Dobson.
This is a report of the treatment of four patients suffering from a syndrome consisting of a single delusion in association with depression. The tendency of monodelusional syndromes to respond to a pimozide provides a rationale for nosological organisation.
It has been shown that the activation of T cells by an anti-idiotypic antibody (anti-Id) TB71 containing an internal image of the corresponding mycobacterial antigen (38 kDa) was achieved by the interaction of anti-Id TB71 with the T cell receptor complex (CD3/Ti). The accessory cell requirement in this response could not be replaced by anti-Id TB71 coupled to Sepharose beads and was not inhibited by Fc receptor blockade. When taken together with the finding that anti-Id TB71-induced proliferation of a T cell clone was restricted by determinants encoded by the major histocompatibility complex, these findings suggested that anti-Id TB71 was presented to 38-kDa antigen-reactive T cells by the same mechanisms as conventional antigenic determinants. That is, both stimulated T cells through the CD3/Ti complex and had to be presented in the context of class II molecules on accessory cells. The finding that the disruption of the integrity of the anti-Id TB71 combining site did not affect T cell responsiveness although antibody binding was ablated implied that anti-Id TB71 may be partially degraded and re-expressed with MHC class II determinants.
Human lymphoproliferative responses to a rabbit anti-idiotypic antibody (anti-Id TB71) and the corresponding mycobacterial protein antigen [38,000 molecular weight (MW)] have been investigated in a number of donors. It was found that responsiveness to anti-Id TB71 correlated with responder and non-responder (four subjects each) status to the 38,000 MW antigen. Furthermore, the induction of T-cell proliferation by both the 38,000 MW antigen and the anti-Id TB71 was dependent on accessory cells. When taken together with the concordance between the 38,000 MW antigen and anti-Id responsiveness, this implies that the 38,000 MW antigen and anti-Id TB71 stimulate related, or at least partially overlapping, repertoires of T cells. This was confirmed by the finding that cloned T cells reactive with the 38,000 MW antigen also proliferated in response to the anti-Id TB71. These observations are readily explained if the anti-idiotypic antibody contains an internal image of, and can therefore mimic, the antigen.
Peripheral blood and bronchoalveolar lavage lymphocyte subpopulations have been evaluated in 14 patients with pulmonary sarcoidosis and eight normal subjects, monoclonal antibodies of the leu series being used. No significant alterations of T lymphocyte subpopulations were found in the peripheral blood of sarcoidosis patients. There was, however, a significantly greater proportion of T suppressor-cytotoxic cells (36.0 (SD 17.6%] in the bronchoalveolar lavage fluid of patients than of normal subjects (15% (5.6%); p less than 0.01), but a decrease in the proportion of T helper-inducer cells (51.1% (18%) v 79.3% (9%). These changes correlated with the duration of the disease but not with other clinical, radiological, physiological, or biochemical criteria. Patients were followed up for six to 20 months and five patients had a repeat bronchoalveolar lavage and lymphocyte subpopulation evaluation after three to 14 months. The initial pulmonary T lymphocyte subset proportions were not predictive of clinical, physiological, or radiological alterations during follow up. There was also no consistent pattern in the relationship between change in T subset proportions and change in clinical physiological, and radiological features in the five patients having a repeat lavage. Lymphocyte surface marker studies may indicate immunopathogenetic mechanisms in sarcoidosis but do not appear to be good predictors of clinical outcome.
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Supernatants from clones of human T lymphocytes that were responding to a purified Mycobacterium tuberculosis antigen were able to activate macrophages and macrophage-like myeloma cells (U937) to release increased amounts of the microbicidal agent hydrogen peroxide. The activity was not neutralized by monoclonal antibody against interferon-gamma (IFN-gamma), was greater than could be accounted for by the IFN-gamma activity in the supernatants, and was separated from IFN-gamma by high performance liquid chromatography. It is evident that IFN-gamma is not the only macrophage activator released by T lymphocytes responding to microbial antigen, and may not even be the main one to enhance antimicrobial activity in infections such as tuberculosis.
In order to explore structural differences between membrane and secreted immunoglobulins the buoyant densities of mouse immunoglobulin (Ig) heavy (H) chains were compared by isopycnic centrifugation in CsCl containing guanidine hydrochloride. The buoyant densities, under denaturing conditions, of mouse myeloma protein MOPC 21 IgG, MOPC 315 IgA and MOPC 104E IgM H chains were consistent with their carbohydrate contents. Mouse membrane IgM and MOPC 104E-secreted IgM H chains were of equal density. The buoyant densities of MOPC 104E-secreted IgM and spleen-cell-secreted IgM H chains were indistinguishable. The IgD-like membrane H chain was denser than membrane IgM H chain, and its carbohydrate content was calculated to be 15.5%. The resolution of the technique was sufficient to conclude that the apparent 1500 mol.wt. difference, as determined by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis, between membrane and secreted IgM H chains was due to peptide rather than to carbohydrate. The results also imply that intact membrane IgM and IgD bind detergent and are thus integral membrane proteins.