Fig. 9.38 The cellular polarization of T cells during specific antigen recognition allows effector molecules to be focused on the antigen-bearing target cell. The example illustrated here is a Cd8 cytotoxic T cell. Cytotoxic T cells contain specialized lysosomes called cytotoxic granules (shown in red in the left panels), which contain cytotoxic proteins. Initial binding to a target cell through adhesion molecules does not have any effect on the location of the cytotoxic granules. Binding of the T-cell receptor causes the T cell to become polarized: reorganization within the cortical actin cytoskeleton at the site of contact aligns the microtubule-organizing center (MToC), which in turn aligns the secretory apparatus, including the Golgi apparatus (Ga), toward the target cell. proteins stored in cytotoxic granules derived from the Golgi are then directed specifically onto the target cell. The photomicrograph in panel a shows an unbound, isolated cytotoxic T cell. The microtubule cytoskeleton is stained in green and the cytotoxic granules in red. note how the granules are dispersed throughout the T cell. panel b depicts a cytotoxic T cell bound to a (larger) target cell. The granules are now clustered at the site of cell–cell contact in the bound T cell. The electron micrograph in panel c shows the release of granules from a cytotoxic T cell. panels a and b courtesy of G. Griffiths. panel c courtesy of e. podack.
Fig. 9.39 The different types of effector T-cell subsets produce different effector molecules. Cd8 T cells are predominantly killer T cells that recognize peptide:MhC class I complexes. They release perforin (which helps deliver granzymes into the target cell) and granzymes (which are pro-proteases that are activated intracellularly to trigger apoptosis in the target cell), and often also produce the cytokine IFn-γ. They also carry the membrane-bound effector molecule Fas ligand (Cd178). When this binds to Fas (Cd95) on a target cell it activates apoptosis in the Fas-bearing cell. The various functional subsets of Cd4 T cells recognize peptide:MhC class II complexes. Th1 cells are specialized to activate macrophages that are infected by or have ingested pathogens; they secrete IFn-γ to activate the infected cell, as well as other effector molecules. They can express membrane-bound Cd40 ligand and/or Fas ligand.
Cd40 ligand triggers activation of the target cell, whereas Fas ligand triggers the death of Fas-bearing targets, and so which molecule is expressed strongly influences Th1 function. Th2 cells are specialized for promoting immune responses to parasites and also promote allergic responses. They provide help in B-cell activation and secrete the B-cell growth factors IL-4, IL-5, IL-9, and IL-13. The principal membrane-bound effector molecule expressed by Th2 cells is Cd40 ligand, which binds to Cd40 on B cells and induces B-cell proliferation and isotype switching (see Chapter 10). Th17 cells produce members of the IL-17 family and IL-22, and promote acute inflammation by helping to recruit neutrophils to sites of infection. T cells produce inhibitory cytokines such as IL-10 and TGF-β that may act at a distance, but also exert inhibitory actions such as sequestration of B7 and IL-2, which act via cell–cell interactions.