Biomedical Engineering Reference
In-Depth Information
6
NF-
κ
B in the Innate
Immune System
Matthew S. Hayden and Sankar Ghosh
CONTENTS
6.1
6.2
NF-
κ
B in Barrier Function .......................................................................... 108
6.3
Development of Innate Immune Cells............................................. 109
6.3.2
Survival of Cells of the Innate Immune System ............................. 111
6.4
NF-
κ
B and PRRs ......................................................................................... 112
6.4.1
TLR Signaling to NF-
κ
B ................................................................. 114
6.4.1.1
MyD88-Dependent Signaling ........................................... 115
6.4.1.2
TRIF-Dependent Signaling............................................... 116
6.4.1.3
Negative Regulation of TLR Signaling............................ 117
6.4.2
NF-
B and CARD-Carrying PRRs ................................................. 117
6.4.2.1
κ
CATEPILLER-NODs ....................................................... 118
6.4.2.2
RIG-I and MDA5.............................................................. 118
6.5
B and the Innate Response to Pathogens............................................ 120
NF-
κ
6.1
INTRODUCTION
As discussed in
Chapter 1
, NF-
B was discovered from studies on the immune system.
These studies led to the appreciation of the multiple roles played by NF-
κ
B during the
initiation, maintenance, and resolution of the immune response. The mechanisms of
NF-
κ
B signaling have been discussed in detail in
Chapters 3
,
4
, and
5
; therefore, in
this chapter and the next, we will focus on the biological role of NF-
κ
κ
B in the immune
system. All of the mammalian NF-
B, and IKK family members have been
knocked-out in mice and analysis of perturbations in the immune responses of these
mice have underscored the important role of NF-
κ
B, I
κ
B in this crucial aspect of physiology.
The immune system can be broadly divided into two arms — innate and
adaptive. The innate immune system includes barriers that prevent pathogen entry;
germline encoded pattern recognition receptors (PRRs) that identify pathogens;
soluble antimicrobial effectors; and various cellular components with antimicrobial
κ
107
