CHAPTER 3 Recognition and Response

Two micrographs show stimulated and unstimulated T cells. — On stimulation (right), the interleukin-2 receptor alpha (IL-2Ra) chain (yellow) is up-regulated on T cells (blue), increasing affinity of the IL-2 receptor for IL-2.

Learning Objectives

After reading this chapter, you should be able to:

Explain how receptor clustering and localized secretion enhance the signaling of small molecules between immune cells.
Offer one example each of an adaptive immune receptor, an innate immune receptor, and a cytokine receptor in which one receptor protein chain may be used in combination with more than one partner chain to alter the nature of ligand specificity.
State where you would expect to find receptors of the adaptive and innate immune systems within the context of the cell and correlate the ligands and receptors of the two types of immune cells with their signaling outcomes.
Draw, and then compare and contrast, the structural features of T- and B-cell receptor complexes, indicating the presence of immunoglobulin domains, coreceptors, and signal transduction mediators.
Explain the common features of the cell signaling pathways used by innate, adaptive, and cytokine receptors.

All cells in a multicellular organism must receive and respond to signals derived from other cells to know when to grow, divide, differentiate, connect, disperse, or die, but cells of the immune system face particular challenges: (1) they must also interact with and eliminate a vast spectrum of potentially dangerous infectious organisms and toxins and (2) because of the widely separated distribution of immune cells among all the other organs of the body, they must be able to communicate with one another over long distances. In every type of immune stimulation, the immune system cell must receive a molecular signal via a membrane-bound or intracellular receptor, and translate the receipt of that signal into a meaningful cellular response such as cell division or differentiation.

In this chapter, we will briefly review common features of cellular receptors and highlight how those shared receptor properties have been adapted by the immune system for its particular use. Next, we will focus on the structure and function of the antigen receptors of the adaptive immune response, B- and T-cell receptors (BCRs and TCRs), and the molecules with which they interact. We will briefly discuss innate immune receptors and describe some of the properties that are shared by innate and adaptive immune receptors. The receptor section of this chapter will close with a discussion of cytokine receptors and their ligands and introduce a specialized family of cytokines, the chemokines, whose role it is to facilitate the movement of immune cells to the regions where they are needed.

The next section will address the concept of signal transduction. Subsequent to a binding interaction between a receptor and its cognate (matching) ligand, the responding cell must communicate knowledge of this receptor-ligand interaction to members of molecular signaling pathways that can evoke the appropriate cellular response. This process is referred to as signal transduction. The end results of signal transduction pathways are changes in the behavior of the responding cell. These changes, which collectively represent the outcome of (or the response to) the receptor’s encounter with its ligand, might include some combination of cell division, differentiation, movement, altered metabolic status, alteration in the expression of surface or cytoplasmic molecules, or secretion of new compounds such as chemokines or cytokines.

The final section of the chapter will summarize some of the biological outcomes of immune system recognition, setting the stage for the chapters that follow.