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R Lefever

Publications and source records attributed to R Lefever.

At least 19 recordsLinked to original sources
PubMed1992

On the kinetics and optimal specificity of cytotoxic reactions mediated by T-lymphocyte clones.

Using the chromium release assay and the single cell assay in agarose, we study the cytotoxic reaction of the MHC-restricted T lymphocyte clones P89:15 and P1:3, which recognize distinct but specific tumour antigens on the surface of syngeneic P815 mastocytoma cells. We propose a mathematical model which describes these experiments, accounts for the strongly non-Michaelian behaviour of the reaction and permits us to estimate the kinetic parameters characterizing effector-target conjugation and lethal hit delivery. The results show that the binding and lytic activity of effector cells is modulated by the number of targets bound to them. The binding of a second target by an effector having already a target bound is facilitated; on the other hand, an effector having bound two targets delivers a lethal hit more slowly than one with a single target bound. We investigate the role of these kinetic properties in the competition between the process of tumour progression due to cancer cell replication and the process of tumour regression due to T lymphocyte cytotoxic activity. For both clones, we estimate the effector-target ratio beyond which rejection prevails. This ratio is nine times larger for P1:3 than for P89:15. Furthermore, our analysis suggests that there exists an optimal specificity minimizing this ratio. Deviations from this optimum, be it in the sense of an increase or decrease of specificity, tends to stabilize the tumoural state: a situation which in the broader context of the immune response evolution and regulation can be viewed as an immune response dilemma.

Animals↗
PubMed1981

Voltage-noise-induced transitions in electrically excitable membranes.

A quantitative study of the steady-state behavior of the sodium and potassium conductance for the Hodgkin-Huxley axon under the influence of an externally driven voltage noise is reported. The dichotomous Markov noise (random telegraph signal) considered allows for an exact evaluation of the stationary probability density of the conductances. Phase diagrams are constructed to represent the response of the system as a function of the amplitude and the correlation time of the noise. The results obtained for the Hodgkin-Huxley axon are compared with some molecular models used in the literature.

Animals↗
PubMed1979

"More pay for me".

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Family Practice↗