Page 550 - Veterinary Immunology, 10th Edition

VetBooks.ir Apoptosis

Cells can kill themselves. Old, surplus, damaged, or abnormal cells
that would otherwise interfere with normal tissue functions can be

persuaded to die as necessary. This cell suicide is called apoptosis.
Apoptosis is carefully regulated and must only be triggered when a
cell must die. Structurally, apoptosis is characterized by membrane
blebbing, nuclear fragmentation, and cell death without lysis. These
dying cells are usually phagocytosed by macrophages.

There are two major pathways of apoptosis: the extrinsic or death
receptor pathway and the intrinsic or mitochondrial pathway. The
extrinsic pathway is triggered by cytokines such as tumor necrosis

factor-α (TNF-α) acting through specific death receptors such as
CD95 (Fas). Death receptors are a family of cell surface receptors
that when activated trigger apoptosis. They all possess an 80-amino
acid cytoplasmic sequence called a death domain. The most
important of these death receptors are CD95 and the tumor necrosis

factor receptors (TNFRs). Death receptors are activated by ligands
expressed on cytotoxic cells. The ligands bind to the receptors and
cause the target cells to assemble multiple adaptor proteins into a

signaling complex. This complex then activates initiator caspase-8
and -10 (Fig. 18.2).

FIG. 18.2 The role of the three different types of caspase in
inflammation and apoptosis. The inflammatory caspases are
described in Chapter 3.

The mitochondrial pathway, in contrast, is triggered by noxious

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