Immune system, genetics and regulation / edited by Eli E. Sercarz, Leonard A. Herzenberg, C. Fred Fox.

  • ICN-UCLA Symposium on the Immune System (1977 : Park City, Utah)
Date:
1977
Catalogue details

Licence: Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)

Credit: Immune system, genetics and regulation / edited by Eli E. Sercarz, Leonard A. Herzenberg, C. Fred Fox. Source: Wellcome Collection.

    694/792 (page 670)
    670 82. MARTIN С. RAFF AND DURWARD LAWSON Using mast cells as a model system, we shall discuss the membrane events occurring during two aspects of cell signalling- the transduction of extracellular signals into intracellular signals by cell surface receptors and the secretion of chemi¬ cal signals by exocytosis. MEMBRANE RECEPTORS AS TRANSDUCERS Membrane receptors have two functions : they bind specific ligands and communicate this fact to the cell interior. It is useful to divide this transduction process into three opera¬ tionally-defined steps: (i) the binding of ligand (the 'first message'); (ii) the change in the receptor and/or the ligand that initiates the next event; and (iii) the generation of an intracellular signal - the 'second message'. In most cases, one ligand binds to one receptor and the interaction probably induces a conformational change in the receptor and/or the ligand, although in no case has this been directly demonstrated. In the immune system, the stimulation of basophils, mast cells and possibly lymphocytes by antigen, antibody or lectins re¬ quires that the receptors be cross-linked by multivalent ligands; the reason for this requirement remains a mystery. There are only two known ways of generating intracellular sig¬ nals following the binding of ligands to surface receptors: (i) increasing or decreasing the activity of a plasma membrane enzyme (such as adenyl cyclase) or (ii) changing the permea¬ bility of the membrane to small molecules (such as ions) - both of which lead to a change in the intracellular concentra¬ tion of biologically important molecules which, in turn, serve as the second messages. Complexity of lymphocyte responses Although lymphocyte activation has been a popular model for studying the early steps in cell triggering, the systems have been too complex to resolve the molecular events occurr¬ ing at the level of individual receptors. The responses usually involve cell differentiation and/or proliferation and require complex cell interactions. In order to activate a sufficiently large proportion of the cells, various polyclonal activators are used, most of which bind to a variety of cell surface molecules, only some of which are probably involved in the activation process. The problem can be illustrated by considering the com¬ plexity of cell interactions involved in the most commonly studied lymphocyte model - the proliferative response of T lymphocytes induced by the lectins phytohaemagglutinin (PHA) and Concanavalin A (Con A). There is increasing evidence in guinea pigs that these responses are absolutely dependent on macrophages (3,4). One of us (MCR), in collaboration with