Membrane Microdomains and Cell Communication in the Immune System
1. Structure and molecular composition of the plasma membrane in eukaryotic cells. Modelling of the plasma membrane by in vitro model membrane systems.
2. Microdomain structure of plasma membranes: experimental evidence from model membranes and live cells. The nature of microdomains: lipid rafts and caveolae.
3. The levels of molecular organization in the plasma membrane of cells: microdomains and macrodomains? Microscopic evidence of hierarchical organization. The technologies to study the fine structure/dynamics of cell membranes: Principles of Single Particle Tracking (SPT) and CLSM colocalization/FRET.
4. Lipid and protein markers of membrane microdomains in cells. Methods to detect constitutive or induced association of membrane proteins with microdomains. Strategies to study the function of lipid rafts.
5. The actin-cytoskeleton as a ’hardware’ in coordination of membrane raft aggregation and formation of signaling platforms for cell activation or cell death. The Vav/WASP signals as coordinators of cytoskeletal remodeling.
6. The role of lipid rafts in regulating the signal transduction by antigen-receptors and lymphocyte maturation in the immune system: B-cells, T-cells, mast-cells. The role of lipid rafts in the function of cytokine (IL-2, IL-15) receptors. Genetic manipulations in understaning the function of IL-2 receptor complex.
7. The role of lipid rafts in innate immunity: The supramolecular organization of the LPS receptor complex and the initiation of inflammatory responses. The role of lipid rafts in compartmentation of antigen presenting molecules (MHC-I, MHC-II) in antigen presenting cells. Effect of this compartmentation on T-cell effector functions and cell death.
8. The Immunological Synapse (IS): models, experiments leading to IS concept. Microscopic evidence of IS. Setting up different stages of synapse formation in the IS. The spatio-temporal arrangement and function of T-cell IS.
9. Different immunological synapses: B-cell/T-cell; macrophage/T-cell; dendritic cell/T-cell; target cell/NK cell synapses. Structure and operation. Synaptic relay race in the immune system.
10. Analogies and differences between neuronal and immunological synapses: lessons from each other and general functional conclusions.
11. Membrane targets in the lymphocytes for signaling therapy of immunological disorders.
12. Membrane microvesicles, exosomes. Their origin, formation and composition. The role of microvesicles in regulation of the immune response.
13. Membrane nanotube networks between immune cells. How the nanotubes grow out? Material transport across nanotubes and their possible regulatory function in the immune system during infections.
Matkó J, Szöllősi J.: Regulatory Apects of Membrane Microdomain (Raft) Dynamics in Live Cells: A Biophysical Approach. In: “Membrane Microdomain Signaling: Lipid Rafts in Biology and Medicine” 2004. (ed. by M. Mattson), pp. 15-46. Humana Press, Totowa, NJ.
Friedl P, Storim J.: Diversity in immune-cell interactions: states and functions of the immunological synapse. Trends in Cell Biology 2004. 14: 557-567.
Gombos I, Kiss E, Detre C, László G, Matkó J: Cholesterol and sphingolipids as lipid organizers of the immune cells’ plasma membrane: Their impact on the functions of MHC molecules, effector T-lymphocytes and T-cell death. (Review) Immunology Letters 2006. 104: 59-69.