Page 65 - Veterinary Immunology, 10th Edition

permeabilization, the release of cytochrome c into the cytoplasm,
VetBooks.ir the formation of an apoptosome and activation of lethal caspase-9.

Apoptotic cells are characterized by distinctive morphological
changes. They form apoptotic bodies. These cell fragments are

destroyed by other phagocytes before their plasma membranes
rupture and, as a result, apoptosis does not trigger inflammation.

Pyroptosis

Pyroptosis is initiated in response to infections and other irritants
that generate inflammasomes. These inflammasomes activate the
inflammatory caspases, caspase-1 and caspase-11. (These are
distinct from the caspases that mediate apoptosis) (see Fig. 2.9).

There is no loss of mitochondrial integrity, no DNA cleavage, and
apoptotic bodies are not formed. Instead, the plasma membrane
ruptures and releases cellular contents including IL-1 and IL-18
into the tissues and thus causes inflammation.

Necroptosis
Necroptosis is triggered by death receptors such as TNFR, nucleic
acid sensors, or by TLR-signaling. They activate receptor activating

kinases and form molecular complexes called necrosomes.
Together with proteases and kinases, they generate a pore-forming
protein that inserts itself into the cell wall and allows the escape of

cellular contents. Mitochondria are not involved in necroptosis.
Like pyroptosis, necroptosis causes inflammation because of the
escape of intracellular DAMPs such as HMGB1 and interleukin-33
(IL-33).

Mitochondria provide a link between PAMPs and DAMPs.
Mitochondria are cytoplasmic organelles that generate energy for

cells. They evolved from intracellular bacteria and retain many of
their original bacterial features. Indeed, in many respects they act
like intracellular bacteria. For example, they have their own DNA
that is rich in unmethylated CpG. When cells die, broken

mitochondria may release large amounts of this DNA that can bind
TLR9 and trigger inflammation. Mitochondria, like bacteria, also
contain proteins with a formyl group at their amino termini. When
these formylated proteins escape, they bind and activate neutrophil

receptors. These neutrophils leave blood vessels and move into

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