Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

1300 Chapter 24: The Innate and Adaptive Immune Systems
membrane of Gram-negative bacteria; TLR5 recognizes the protein that forms
the bacterial flagellum; and TLR9 recognizes short, unmethylated sequences of
bacterial, viral, or protozoan DNA, called CpG motifs, which are uncommon in
vertebrate DNA.
In addition to TLRs, vertebrates use several other families of PRRs to detect
pathogens. One is the large family of NOD‐like receptors (NLRs). Like TLRs,
NLRs have leucine-rich repeat motifs, but they are exclusively cytoplasmic and
recognize a distinct set of bacterial molecules. Individuals who are homozygous
for a particular mutant allele of the NLR gene NOD2 have a greatly increased
risk of developing Crohn’s disease, a chronic inflammatory disease of the small
intestine, possibly triggered by a bacterial infection. Another class of PRRs consists
of RIG‐like receptors (RLRs), which are members of the RNA helicase family
of proteins. They are also exclusively cytoplasmic and detect viral pathogens. A
fourth class of PRRs consists of C‐type lectin receptors (CLRs), which are transmembrane
cell-surface proteins that recognize carbohydrates (which is why they
are called lectins) on various microbes. Table 24–1 summarizes some PRRs and
their ligands and locations in cells. Collectively, these and other PRRs act as an
alarm system to alert the innate and adaptive immune systems that an infection
is brewing (Movie 24.1).
When a cell-surface or intracellular PRR binds a PAMP, it stimulates the cell
to secrete a variety of cytokines and other extracellular signal molecules. Some of
these inhibit viral replication, but most induce a local inflammatory response that
helps eliminate the pathogen, as we now discuss.
Activated PRRs Trigger an Inflammatory Response at Sites of
Infection
When a pathogen invades a tissue, it activates PRRs on or in various cells of the
innate immune system, resulting in an inflammatory response at the site of infection.
The inflammatory response depends on changes in local blood vessels and is
characterized clinically by local pain, redness, heat, and swelling. The blood vessels
dilate and become permeable to fluid and proteins, leading to local swelling
and an accumulation of blood proteins that aid in defense. At the same time, the
endothelial cells lining the local blood vessels are stimulated to express cell adhesion
proteins, which promote the attachment and escape of white blood cells or
leukocytes (see Figure 19–29B), adding to the local swelling; initially neutrophils
escape, followed later by lymphocytes and monocytes (the blood-borne precursors
of macrophages).
Table 24–1 Some Pattern Recognition Receptors (PRRs)
Receptor Location Ligand Origin of ligand
Toll-like receptors (TLRs)
TLR3 Endolysosomal system Double-stranded RNA Viruses
TLR4 Plasma membrane Bacterial lipopolysaccharide (LPS); viral coat proteins Bacteria; viruses
TLR5 Plasma membrane Flagellin Bacteria
TLR9 Endolysosomal system Unmethylated CpG DNA Bacteria, viruses, protozoa
NOD-like receptors (NLRs)
NOD2 Cytoplasm Degradation products of peptidoglycans Bacteria
Retinoic acid-inducible gene 1-like receptors (RLRs)
RIG1 Cytoplasm Double-stranded RNA Viruses
C-type lectin receptors (CLRs)
Dectin1 Plasma membrane β-Glucan Fungi