Page 615 - Veterinary Immunology, 10th Edition

VetBooks.ir

FIG. 20.5 Peripheral tolerance through clonal anergy will develop if
a TCR is stimulated by antigen in the absence of simultaneous co-
stimulation through the CD28/CD80 or CD28/CD86 pathway.

Binding to the TCR by an antigen in the absence of co-stimulation
activates the tyrosine kinases and phospholipase of the T cell and
2+
raises its intracellular Ca . This results in enhanced production of
IκB that inhibits NF-κB. This prevents the cell from making

cytokines, especially IL-2. Tolerant Th1 cells produce less than 3%
of normal IL-2 levels and much less IFN-γ and TNF-α. Once
induced, this “anergy” can last for several weeks.

Triggering of T cell responses normally requires prolonged
interactions with antigen-presenting cells (APCs). Tolerance
induction, on the other hand, is characterized by relatively short
interactive episodes. Thus a key difference between T cell activation
and anergy may simply be the duration of their encounter with

APCs.
Very high doses of an antigen can induce a form of clonal anergy
called immune paralysis (Fig. 20.6). The high doses of the antigen

probably bypass APCs, reach the Th cell receptors directly, and in
the absence of co-stimulation, trigger paralysis.

615