Page 594 - Veterinary Immunology, 10th Edition

cells and macrophages. Macrophages stimulate NK cell activities
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with TNF-α and IL-12.

Once activated, NK cells kill target cells through either a
perforin/granulysin/NK-lysin pathway or through the death
domain pathway involving CD95L. NK cell granules are stored

preformed in resting NK cells (in contrast to cytotoxic T cells, which
only produce theirs on demand). Once an NK cell encounters a
target cell, a synapse forms at the contact site. Activating KIRs
induces MHC molecules to form a ring around a cluster of adhesion

molecules. At the center of the synapse, there is a cSMAC through
which NK cell granule contents can pass. Receptors and signaling
molecules also segregate in the cSMAC, whereas integrins and talin
accumulate in the pSMAC. Inhibitory KIRs, in contrast, prevent the

localization of lipid rafts to the immune synapse.
Perforins, granulysin, and NK-lysin are found in NK cell
granules, and their expression is increased by exposure to IL-2 and
IL-12. NK cell perforin is a protein of 70 to 72 kDa (slightly larger

than that produced by T cells). It produces small (5 to 7 nm dia)
channels in target cell surfaces. Presumably, granzymes are injected
into the target cells through the perforin channels.

Functions

Unlike T and B cells that circulate as resting cells and so require
several days to become fully activated, NK cells are “on call” and
can be rapidly activated by IFNs released from virus-infected cells
or by IL-12 from stimulated macrophages. As a result, NK cells

promptly attack tumors and virus-infected cells. They participate in
innate defenses long before antigen-specific primary adaptive
responses can be generated.

NK cells kill some tumor cells, xenografts, and virus-infected cells
(Fig. 19.11). Thus they are active against herpesviruses, influenza,
and poxviruses. Some Ly49 molecules on mouse NK cells can also
recognize viruses directly so that, for example, they can kill
cytomegalovirus-infected cells. NK cells can also kill bacteria such

as Staphylococcus aureus, Mycobacteria, and Salmonella typhimurium;
protozoa such as Neospora caninum; and some fungi.

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