So how is a threat detected?
Well, there are these Pattern Recognition Receptors
- PRRs, that can recognize infectious agents.
And what they recognize on the
infectious pathogen are structures
that are called Pathogen-Associated
Molecular Patterns or PAMPs, P-A-M-P.
Also, Pattern Recognition Receptors, as well
as recognizing PAMPs on foreign infectious
agents can recognize structures associated
with damage to our own body cells.
And we call these structures
Damage-Associated Molecular Patterns.
So Pattern Recognition Receptors
can recognize both PAMPs and DAMPs.
And these can be present on the cell
surface or sometimes inside cells,
and these may be on pathogen cells or
they may be on our own body cells.
What is important to appreciate, is that although this
recognition is often described as being broadly
specific, what is actually being recognized is
recognized in a very, very highly specific way.
So for example, we’ll mention a few Pathogen-Associated
Molecular Patterns in a few moments.
One of them is called
lipopolysaccharide or LPS.
LPS is found on
And there are lots of different
types of Gram-negative bacteria.
So LPS is shared between several different bacteria but
the recognition of LPS is very, very highly specific.
So recognition is structurally-specific but what is recognized
is common to whole groups of organisms or host cells.
These Pattern Recognition Receptors can be
inside cells, in other words, intracellular.
And if they’re intracellular, if they’re
inside a cell, they may be present on the
endosomes within the cell or they may be
present within the cytosol of the cell.
Alternatively, they may be present on the surface of
cells, cell surface Pattern Recognition Receptors.
Or indeed, they may be released or secreted from
cells as soluble Pattern Recognition Receptors.
You can now look at a number of different
Pattern Recognition Receptors and the PAMPs that they recognize.
Let’s start with endosomal
Pattern Recognition Receptors.
There is a group of 10 or so Pattern Recognition
Receptors that are called toll-like receptors.
Couple of examples for you now; TLR3, toll-like
receptor recognizes the PAMP viral double-stranded RNA.
TLR7 and TLR8 recognize
viral single-stranded RNA.
Whereas TLR9 recognizes a particular nucleotide sequence
within the DNA of bacteria, called bacterial unmethylated CpG.
Let’s now turn to cytosolic
Pattern Recognition Receptors.
NOD-1 (nucleotide-binding oligomerization
domain-containing protein-1) and NOD-2.
These recognize bacterial
These structures are found
on Gram-positive bacteria.
So again, shared between many different
bacteria but the recognition of
peptidoglycan by NOD-1 and NOD-2 is highly
specific for that particular structure.
RIG-1 (retinoic acid-inducible gene 1)
recognizes viral double-stranded RNA.
And as a third example of a cytosolic Pattern
Recognition Receptor, NLRP3 (NOD-like receptor family,
pyrin domain containing 3) which is part of the
inflammasome which we’ll discuss in a few seconds.
This recognizes bacterial
Cell surface Pattern Recognition Receptors; TLR2,
again recognizes bacterial structures that are shared
between many different bacterial species, various
bacterial lipopeptides and lipoproteins.
TLR4 recognises bacterial
And TLR5 recognises
And finally, soluble Pattern
Mannose binding lectin that recognizes
the sugar mannose as its name suggests.
And Ficolin, which recognizes
N-acetylglucosamine, another sugar.
Let’s now turn to Pattern Recognition Receptors
which recognize DAMPs - Damage-Associated
Molecular Patterns or sometimes called
Danger-Associated Molecular Patterns.
These are Pattern Recognition Receptors that recognize
structures produced by our own body cells following damage.
A couple of examples of Pattern
Recognition Receptors present on cell
surfaces that recognize DAMPS: RAGE,
the receptor for advanced glycation
end products as its name suggests
recognizes advanced glycation end products
that are produced by our
own cells in response to damage.
And RAGE, TLR2 and TLR4 recognize
HMGB1 (high mobility group box 1).
So if you were paying attention you’ll see
that RAGE recognizes two
different DAMPs - advanced glycation end products and HMGB1.
Whereas TLR2 and TLR4 are specific not for
advanced glycation end products, but for HMGB1.
And then finally, cytosolic Pattern Recognition
Receptors, involved with a structure called the
inflammasome; NLRP3 recognizes the Damage or
Danger-Associated Molecular Pattern, uric acid.