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Biomedical subjects

G A Rook

Publications and source records attributed to G A Rook.

At least 181 records · Page 10Linked to original sources
PubMed1981

The effect of delayed addition of antigen and 'E' rosetting on the proliferative response to mycobacterial antigens of peripheral blood lymphocytes from normal individuals or from patients with tuberculosis or leprosy.

Some suppressor cells are reported to lose their activity when precultured without stimulus in vitro. We have investigated the role of such suppressors in responsiveness to mycobacterial antigens of peripheral blood mononuclear cells (PBMNC) from patients with leprosy or tuberculosis, or from normal donors. Delayed addition of mycobacterial antigens (Mycobacterium leprae, Mycobacterium vaccae and Mycobacterium tuberculosis), but not of a fungal antigen (Candida albicans) caused enhanced responses using PBMNC from most normal donors, or tuberculoid leprosy (TT/BT) patients. However, the effect was less common using PBMNC from the lepromatous leprosy (BL/LL) group. (P less than 01.01, using M. leprae, relative to the TT/BT group), suggesting that this type of suppression reflects a normal mechanism, which is diminished rather than increased in anergic patients. Delayed addition of antigens to 'E'-rosetting cells did not result in enhanced responses. However, the different effects of 'E'-rosetting on the responses to the mycobacterial antigens of cells from normals, TT/BT and BL/LL patients, suggested that there may be two types of proliferative response to these antigens.

Antigens, Bacterial↗
PubMed1981

Prostaglandin-dependent regulation of the in vitro proliferative response to mycobacterial antigens of peripheral blood lymphocytes from normal donors and from patients with tuberculosis or leprosy.

The response to soluble mycobacterial antigens of peripheral blood mononuclear cells, from most normal donors, tuberculosis patients or cases of tuberculoid leprosy (TT/BT) was enhanced by the addition of indomethacin. In contrast, indomethacin caused no enhancement of the response of cells from lepromatous leprosy (BL/LL) cases. Moreover the addition of 10-5 M prostaglandin E2 (PGE2) failed to inhibit the proliferative responses of cells from the BL/LL patients, although it markedly inhibited the responses of peripheral blood mononuclear cells from the other groups. The addition of PGE2 or indomethacin to cells which had been precultured for 48 hr had no significant effect on the proliferative responses of cells from any of the groups of donors. These results suggest that a normal, prostaglandin-dependent, indomethacin-sensitive regulatory mechanism is absent from the peripheral blood mononuclear cells of BL/LL patients.

Antigens, Bacterial↗
PubMed1980

Use of the ELISA to screen for anti-thymocyte and anti-beta 2-microglobulin antibodies in leprosy and SLE.

A report is given of the use of the enzyme-linked immunosorbent assay to measure antibody to preparations of human thymocyte membranes (HTMA) and to beta 2-microglobulin. The assay described is simple and rapid, and requires only small quantities of an easily stored membrane preparation. The advantages of this technique over conventional methods involving cytotoxicity are discussed. Raised levels of IgM antibody to beta 2-microglobulin were detected in sera from SLE patients. Raised levels of IgG and IgM antibody to HTMA were found in sera from most active lepromatous cases. Two of eight sera from SLE patients showed raised IgG anti-HMTA, but not raised IgM. An attempt was made to study the subclass of the IgG antibodies found, but when checked against purified human IgG myeloma proteins, the available anti-subclass sera were found to lack the necessary degree of specificity in this assay.

Antigens, Surface↗
PubMed1979

The relevance to protection of three forms of delayed skin-test response evoked by m. leprae and other mycobacteria in mice. Correlation with the classical work in the guinea-pig.

The controversy surrounding the protective role of 'delayed hypersensitivity' in tuberculous guinea-pigs has never been resolved. This controversy has arisen because the term 'delayed hypersensitivity' is used indiscriminately to describe both a type of necrotic skin-test reactivity which does not appear until 4-6 weeks after infection, and also non-necrotic reactions which can be elicited within a few days. Responses closely analogous to both have been characterized in mice immunized with mycobacteria. Simple criteria are described which allow these responses to be distinguished from one another, and from the Jones-Mote phenomenon. The relevance of each type to protection, susceptibility and immunopathology in leprosy, tuberculosis, leishmaniasis and listeriosis is discussed.

Animals↗
PubMed1978

Is the adherent, non-specific 'suppressor' cell from rodent spleens an in vitro artefact?

Mitomycin C-treated cells from the spleens of mice pre-treated with BCG, Corynebacterium parvum, cyclophosphamide or methylcellulose will inhibit the mitogen responses of normal cells in vitro, but extended dose-response studies have shown that such cell populations will also enhance the response if added in very small numbers. The number of cells giving peak enhancement is proportional to the percentage of the spleen cells which are adherent at 72 hr. Such late-adhering cells are not removed by conventional adherence column techniques. The concept of the adherent suppressor T cell is discussed in the light of these findings.

Adhesiveness↗
PubMed1976

The dissociation of adjuvant properties of mycobacterial components from mitogenicity, and from the ability to induce the release of mediators from macrophages.

Twelve preparations from mycobacterial cell walls and culture supernatant fluids were tested for their ability to activate lymphocytes from Balb/c or Nu/Nu mice, and to increase the release of mediators from macrophages in vitro. The peptidoglycolipids (wax D) were B-cell mitogens and induced plaque-forming cells. These properties were lost if the glycopeptide component was removed, leaving the pure lipid, mycolic acid. Neither the glycopeptide fractions, with well-documented adjuvant properties, nor mycobacterial polysacchardie II-activated B cells. Only intact peptidoglycolipid showed synergy with the mitogenic effect of phytohaemagglutinin (PHA) on thymocytes from Balb/c mice. The effect was much smaller than with E. coli lipopolysacharide (LPS) or dextran sulphate. The peptidoglycolipid also enhanced the release of factors from macrophages able to modify the response of Balb/c thymus cells to PHA. In this respect it resembled E. coli LPS. Adjuvant active glycopeptides did not share this property.

Adjuvants, Immunologic↗
PubMed1976

Preliminary evidence for the trapping of antigen-specific lymphocytes in the lymphoid tissue of 'anergic' tuberculosis patients.

Lymphocyte-transformation responses to mycobacterial antigens have been studied, using paired blood and lymph node samples from 'normal' Ugandans, (hernia repairs or orthopaedic cases) or from patients with tuberculosis, Mycobacterium ulcerans infection, or injection abscesses. The results suggest that in some individuals, antigen reactive cells, although absent from the periphery, may be demonstrable in the lymph nodes. This phenomenon is most striking in skin-test negative tuberculosis patients.

Antigen-Antibody Reactions↗
PubMed1976

Immune responses to mycobacteria in mice and men.

This paper contains discussion of a number of mechanisms which may explain the suppression of the cell-mediated immune response during the phase of dissemination of mycobacterial infection in mice and men. However, it is not yet possible to evaluate the relative importance of these mechanisms, or even to say which are the causes and which are the consequences of that disseminaton.

Animals↗
PubMed1975

The potentiating, mitogenic and inhibitory effects on lymphocytes in vitro, of macrophages in the lymph nodes of mice 'overloaded' with mycobacterial products.

The lymph nodes of mice overloaded with mycobacterial products, either by the injection of whole or ultrasonicated organisms, or as a consequence of severe infection with Mycobacterium ulcerans, contain phagocytic cells which cause spontaneous transformation of the lymph node cells in a low volume, high cell density culture system. This spontaneous mitosis is unaffected by trypsinization but is inhibited by specific antigen and by PHA, and eliminated by treatment with carbonyl iron. Replacement of the macrophages removed with carbonyl iron by a critical number of peritoneal cells, restores the spontaneous transformation. Normal lymph node, thymus or peritoneal lymphocytes will also undergo mitosis if small numbers of peritoneal cells are added to them. This phenomenon therefore appears not to be antigen-dependent, but is probably due to a mediator released from macrophages. The possible role of this phenomenon in the pathogenesis of mycobacterial disease and the 'overloading' of T lymphocytes in vivo is discussed, with reference to similar macrophage-dependent mechanisms reported in other systems.

Animals↗
PubMed1975

The immunological consequences of antigen overload in experimental mycobacterial infections of mice.

Mice infected in the tail with M. ulcerans developed transient cell-mediated immunity which disappeared as the bacterial load increased. Lymph node cells from animals in this late phase of the disease transformed spontaneously in vitro. This transformation was inhibited by mycobacterial antigen. Lymph node cells from mice injected intravenously with 10(8) or 10(9) BCG also transformed spontaneously in vitro. Such animals did not become foot pad test-positive. Evidence is presented that the spontaneous transformation may represent an accumulation of specifically sensitized cells due to trapping in nodes overloaded with persistent antigen. The relevance of such a phenomenon to 'desensitization' in human and animal disease is discussed.

Animals↗
PubMed1975

Preliminary taxonomic studies on the leprosy bacillus.

Antigens extracted from leprosy bacilli obtained from infected human and armadillo tissues have been examined by immunodiffusion analysis with serum samples from lepromatous patients and with immune sera raised in rabbits. Using the best combinations of serum and antigen extracts, 12 antigenic constituents were found in the leprosy bacilli. Six of these were antigens common to all mycobacteria and nocardiae, 4 were specific to the leprosy bacillus and the position of 2 could not be determined. Groups ii and iii antigens (i.e. those associated with the slow growing and fast growing subgenera of mycobacteria) were not found in theleprosy bacillus, suggesting some relationship with M. vaccae and similar strains, in which these antigens are also missing. Lymphocyte transformation tests performed on lymph node cells of mice infected or immunized with leprosy bacilli also showed the leprosy bacillus to have a closer relationship with M. vaccae than with other mycobacteria.

Animals↗
PubMed1970

Antilymphocyte serum and tissue culture used to investigate role of cell-mediated response in viral encephalitis in mice.

Antilymphocyte serum given to suppress selectively the cell response to Langat virus in Swiss albino mice prolonged the average survival times. In vitro, lymph-node cells from virus-immunized mice were strongly cytotoxic for syngenic non-neuronal brain cells infected with virus. The implications of these findings are discussed, with particular reference to the concept of autoimmunity.

Animals↗