Page 237 - Veterinary Immunology, 10th Edition

are linked to serine and about 10% to threonine. Only about 1/2000
VetBooks.ir of the phosphate is linked to tyrosine. Thus tyrosine

phosphorylation is a rare event. Nevertheless it is a key mechanism
in almost all the signal transduction pathways described in this

book.

Transduction Pathways

Although there are many signal transduction pathways, three play

key roles in the immune system. These involve the generation of the
transcription factors: NF-κB, NF-AT, and STAT.

NF-κB Pathway

The NF-κB pathway is the most significant signal transduction

pathway in the immune system. It is the pathway that is activated
when antigens bind to the T cell and B cell antigen receptors (TCR
and BCR); when PAMPs bind to the pattern-recognition receptors
(PRRs), such as the TLRs and NODs; and when TNF-α binds to its
receptor. Thus NF-κB plays a critical role in both innate and

adaptive immunity. The term NF-κB refers to a family of five
transcription factors. These factors can form many heterodimers
that activate different genes. More than 150 unique stimuli can

activate NF-κB, and more than 150 genes are expressed after NF-κB
activation. In a resting cell, NF-κB is found in the cytosol in an
inactive form bound to a protein called IκB. IκB inhibits NF-κB
activity by masking its nuclear binding site. Thus in resting cells,
NF-κB cannot move to the nucleus or activate genes.

The major NF-κB activation pathway is triggered by
inflammatory cytokines IL-1 and TNF-α, by TLRs, and by antigen
receptors, and it is essential for innate immunity. The signals

induced by these stimuli converge on a central regulator of NF-κB,
the IKK (IκB kinase) complex. This complex consists of multiple
subunits with kinase activity. When activated, IKK phosphorylates
IκB. As a result, the IκB dissociates from the NF-κB and is
destroyed. This releases the NF-κB so that it can enter the nucleus

and activate selected genes including those encoding IL-1β, IL-6, IL-
18, IL-33, TNF-α, GM-CSF, and IL-4. NF-κB also activates the genes
coding for chemokines, proangiogenic factors, adhesion molecules,

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