Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

1334 Chapter 24: The Innate and Adaptive Immune Systems
T C cell
T C cell
centrosome
target cell
T C cell
target cell
(A) (B) (C)
5 µm 5 µm
10 µm
Figure 24–42 Effector cytotoxic T cells killing target cells in culture. (A) Electron micrograph showing an effector
cytotoxic T cell (T C cell) binding to a target cell. The T C cells were obtained from mice immunized with the target cells, which
are foreign tumor cells. (B) Electron micrograph showing a T C cell and a tumor cell that the T C cell has killed. In an animal,
as opposed to a culture dish, the killed target cell would be phagocytosed by neighboring cells (especially macrophages)
long before it disintegrated in the way that it has here. (C) Immunofluorescence micrograph of a T C cell and tumor cell after
immunofluorescence staining with anti-tubulin antibodies. Note that the centrosome in the T C cell is located at the point of
cell–cell contact with the target cell—an immunological synapse. The secretory granules (not visible) in the T C cell are initially
transported along microtubules to the centrosome, MBoC6 which m25.46/24.44 then moves to the synapse, delivering the granules to where they can
release their contents. (A and B, from D. Zagury et al., Eur. J. Immunol. 5:818–822, 1975. With permission from John Wiley &
Sons, Inc; C, from B. Geiger, D. Rosen and G. Berke, J. Cell Biol. 95:137–143, 1982. With permission from the authors.)
An effector T C cell (or an NK cell) can employ one of two strategies to kill the
target, both of which operate by inducing the target cell to activate caspases and
kill itself by undergoing apoptosis. One mechanism uses a protein called Fas
ligand on the killer-cell surface, which binds to a transmembrane receptor protein
called Fas on the target cell; this mechanism is discussed in Chapter 18 (see
Figure 18–5). The other mechanism is the main one used by both NK cells and
T C cells to kill an infected target cell. The killer cell stores various toxic proteins
within secretory vesicles in its cytoplasm that it releases into the synaptic space
by exocytosis. The toxic proteins include perforin and proteases called granzymes.
The perforin is homologous to complement component C9 and polymerizes in
the target-cell plasma membrane (see Figure 24–8), forming a transmembrane
pore that disrupts the membrane and allows the granzymes to enter the target
cell. Once in the cytosol, the granzymes help activate caspases, thereby inducing
apoptosis (Figure 24–43).
perforin
molecules
effector cytotoxic T cell
T C TC T C T C
granzyme
molecules
assembled
perforin
granzymes
channel
infected target cell
procaspase
active
caspase
caspase cascade
apoptotic
target cell
Figure 24–43 The main way that an
effector T C cell (or NK cell) kills an
infected target cell. This simplified
drawing shows how the killer cell releases
perforin and granzymes onto the surface
of an infected target cell by localized
exocytosis at an immunological synapse.
The high concentration of Ca 2+ in the
extracellular fluid causes the perforin to
assemble into transmembrane channels in
the target-cell plasma membrane, allowing
the granzymes to enter the target-cell
cytosol. The granzymes cleave and activate
procaspases to initiate a caspase cascade,
leading to apoptosis (see Figure 18–3). A
single cytotoxic cell can kill multiple target
cells in sequence. It remains a mystery why
the released perforins do not form pores in
the plasma membrane of the killer cell itself
(Movie 24.12 and Movie 24.13).