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Biomedical subjects

P Fitzharris

Publications and source records attributed to P Fitzharris.

62 records · Page 4Linked to original sources

Inhibition of proliferative and suppressor responses in the autologous mixed lymphocyte reaction by serum from patients with systemic lupus erythematosus.

Serum from patients with systemic lupus erythematosus (SLE) prevents the proliferative response of normal T cells when stimulated by autologous or allogeneic non-T cells. The abrogation of proliferation in an autologous mixed lymphocyte reaction (AMLR) with SLE serum is associated with a lack of suppressor T cell generation. Fractionation of SLE sera on sucrose gradients reveals an 18-12 S peak of Raji cell binding material. Fractions with an S value of </=12 S show inhibitory activity in an AMLR.

Adult↗

Effects of activated T cells on natural killing.

Two populations of human blood lymphocytes--one forming rosettes with sheep erythrocytes, the other non-rosetting--are cytolytic in vitro for several long term cultured tumour-derived cell lines. A particular breast cancer-derived target cell (MDA-157) is only killed by the non-rosetting effector. Rosetting cells from normal donors infected or immunized with influenza virus augment cytolytic activity on MDA-157 targets by non-rosetting effector cells. Similar augmenting activity can be induced by incubating the rosetting population with sources of immune (gamma), but not leucocyte (alpha) interferon in vitro. This augmentation of cytolytic activity does not require compatibility at the major histocompatibility locus between the augmenting and effector populations.

Antibody-Dependent Cell Cytotoxicity↗

Insensitivity to interferon of NK cells from patients with systemic lupus erythematosus.

Natural cytotoxicity (NK) by fresh E-rosette-negative (ER-) cells from normal donors was increased after overnight incubation with purified IFN alpha and with supernatants containing IFN gamma. ER- cells from 61% of 23 patients with systemic lupus erythematosus did not show increased cytotoxicity after treatment with IFN alpha. Similarly, ER- cells from nine of 18 patients that were treated with IFN gamma-containing supernatants failed to show increased cytotoxicity. The patients who did not show enhanced cytotoxic responses to IFN had higher mean indices of disease activity than responding patients.

Adult↗

Kinetics of specific in vitro antibody production following influenza immunization.

In vitro specific antibody responses to influenza viral antigens by peripheral blood mononuclear leucocytes following stimulation with influenza virus or pokeweed mitogen have been measured before and at time intervals after influenza immunization in 11 healthy volunteers. There was an early increase in specific antibody produced by lymphocytes stimulated with influenza virus in vitro, in all subjects immunized. The magnitude of the response varied considerably between individuals as did its duration. Virus specific antibody production by cells stimulated with pokeweed mitogen also increased after immunization in all donors. Cells from six of the 11 individuals produced specific antibody in vitro seven days after immunization without antigen or mitogen stimulation. Seven of the 11 subjects had a greater than four-fold increase in serum titre of haemagglutination inhibiting antibody. This study shows an early brisk increase in the ability of lymphocytes to respond to influenza virus in vitro following immunization consistent with a secondary immune response.

Antibodies, Viral↗

Kinetics of specific anti-influenza antibody production by cultured lymphocytes from patients with systemic lupus erythematosus following influenza immunization.

Specific antibody responses to influenza viral antigens produced by cultured peripheral blood mononuclear leucocytes stimulated with influenza virus or pokeweed mitogen (PWM) have been measured in seven patients with systemic lupus erythematosus (SLE) before and at time intervals after influenza immunization. Cells from two patients stimulated with influenza virus in vitro produced high levels of specific antibody 7 days after immunization. Cells from a third patient produced small amounts of specific antibody at day 14. No antibody was produced by cells from the remaining four patients. Responses were of short duration and were not detectable 1 month after immunization. Specific anti-influenza antibody was induced by PWM only from cells of those patients who responded to virus antigen although absolute levels of antibody produced were not as high. In six patients serum haemagglutination inhibiting antibody to influenza virus was measured, and all six had a greater than four-fold increase. The disparity between in vitro antibody production by peripheral blood mononuclear leucocytes and changes in serum antibody suggests that in patients with systemic lupus erythematosus, in vitro functions of peripheral blood lymphocytes do not reflect the immune system as a whole.

Antibodies, Viral↗

Generation of suppressor cells in the autologous mixed lymphocyte reaction.

When challenged with HLA-A, B and DR incompatible cells, T cells which have been primed in an autologous mixed lymphocyte response (AMLR) show an accelerated (day 2) component of their proliferative response, as well as the expected primary-style response at day 5. This early response of AMLR-primed cells to allogeneic stimulation, like the response to rechallenge with autologous cells, is abolished by treatment of the primary culture with BUdR and light. These results suggest that priming in the AMLR is not solely to MHC-private specificities, and that an antigenic element common to autologous and allogeneic cells is recognized. The AMLR also generates cells with suppressor activities. AMLR-primed cells suppress the proliferative responses of fresh T cells from the same donor to autologous or allogeneic stimulation. Limiting numbers of suppressor cells are more effective suppressors of the autologous, than of the allogeneic response. Suppressor activity is reduced but not abolished by treatment with mitomycin C. AMLR-primed cells also suppress pokeweed mitogen-induced antibody production by fresh peripheral blood lymphocytes. In some experiments, specific antigen-induced antibody production is also suppressed.

Antibodies, Viral↗

Separation of spontaneous-killing effector populations by target preference.

Three populations active in human spontaneous cytotoxicity have been identified. Two of these are E-rosette positive, and differ in their adherence to nylon wool. The third is E-rosette negative. The E-rosette positive fraction which does not adhere to nylon consistently does not lyse a breast-cancer-derived target, MDA-157. When tested simultaneously on 4 other tumour target cells lines--Raji, Chang, K562 and Molt 4--however, all three populations are cytolytic. The MDA-157 target is consistently lysed by a nylon-adherent T-cell fraction, irrespective of whether the E rosettes are formed under optimal or the limiting conditions giving only "high-affinity" T cells. The observation that a given effector fraction can lyse one target but not another, whereas other fractions are cytolytic on both, implies that different targets may differentiate effector populations differing in their lytic mechanism.

Animals↗