Page 554 - Veterinary Immunology, 10th Edition

VetBooks.ir Cell Cooperation

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During a primary immune response, CD8 cytotoxic T cells cannot
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respond to infected cells alone. There are about 10 nucleated cells
in a human-sized body and possibly several hundred naïve T cells
with receptors for each individual viral antigen. Clearly it would be
almost impossible for these T cells to find and kill all the cells
expressing corresponding viral antigens without help. In practice,
dendritic cells link processed antigens to MHC class I molecules

and carry them to lymphoid organs, where they are presented to
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CD8 T cells. To respond fully, the CD8 cells must also be co-
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stimulated by CD4 helper cells. Co-stimulation is only effective
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when both the CD8 and CD4 T cells recognize antigen on the same
antigen-presenting cell. Thus a helper T cell first interacts with an
antigen-presenting dendritic cell through CD40 and CD154. The
helper T cells activate the dendritic cells, upregulate their
expression of MHC class I, and stimulate their production of

interleukin-12 (IL-12). Once activated, dendritic cell MHC class I–
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linked peptides bind to CD8 T cells. For complete activation, the
cytotoxic T cells require three key signals. The first is IL-12 from

activated dendritic cells. The second is an antigen-specific signal
from the antigen–MHC class I complex on their target cell. The
third signal comes from IL-2 and IFN-γ produced by the Th1 cells.
Only after all three signals are received will the CD8 T cells
respond.

Different levels of stimulation trigger different activation
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responses in CD8 T cells. As with helper cells, the duration of the
stimulus is important. Although activated cytotoxic T cells can be

triggered by brief exposure to antigen, naïve T cells must be
stimulated for several hours before responding. The required
stimulation time may be shortened by increasing TCR occupancy or
by providing additional co-stimulation. Once activated, naïve CD8 +
T cells begin to divide. They undergo multiple rounds of division to

generate large numbers of cytotoxic effector cells. Calculations have
suggested that they undergo as many as 19 cell divisions in the
days following antigen exposure and they probably divide every 4

to 6 hours. All this is regulated by extracellular signals from the

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