S. 28: Physics of cellular immune reactions

In the present complementary chapter we concentrate on an early immunological process: the stimulation of naive T-cells by a specific class of infected, antigen exposing cells, such as dendritic cells (DC) and macrophages, called “antigen presenting cells” (APC). The proliferation of naïve T-cells can be mediated by transient and long lasting encounters with APCs. We first describe the T-cell stimulation by adhesion induced microdomains, called immunological synapses (IS), whereby the microdomains act as biochemical reaction centers which prevent the access of inhibitors exposing long extracellular chains, such as the phosphatase CD45. We then show how in a secondary reaction large scale (global) reaction spaces are formed by the adhesion induced generation of ring like adhesion zones and cell polarization through actin microtubule crosstalk. The sequential stimulation of T-cells by numerous encounters with antigen presenting cells is explained in terms of the stepwise progress through the cell cycle, with each step being driven by a by certain number (quantum) of interleucine II. We then show that the effects of the SI could be integrated with the help of a transient memory generated by an allosteric enzyme (the guanine exchange factor SOS) which activates the MAPK mediated pathway of cell proliferation.

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Biophysics of Immunology

S.9.A. Hydrophobic-electrostatic membrane coupling and activation of functional proteins.

This supplemental chapter deals with the physics of biological membrane processes mediated by transient coupling of extrinsic proteins to the inner leaflet of plasma membranes or the outer leaflet of intracellular organelles, with major emphasize on the hydrophobic-electrostatic mechanism of protein-to-membrane linkage. We start with the discussion of the protein absorption by electrostatic-hydrophobic interaction of proteins with polybasic sequences to membranes containing phosphatidylserine and phosphoinositides (PIP2, PIP3). We then show various mechanisms of protein adsorption by specific interaction of specific homology domains with lipids. These lipids can thus function as second messenger which transmits external cues into intracellular signaling and can couple signaling pathways initiated by different enzymes. An outstanding example is the stimulation of lymphocytes by transient encounters with antigen presenting cells presented in Chapter 39. Numerous keywords are defined in the Glossary to this Chapter.

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Physics of Functional Membrane Micro-Domains

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