376
Antigen Presenting Cells (APCs)
should be left untouched and nutrient
microorganisms that should be engulfed
and degraded, is obvious. Hence, any sur-
face receptor that allowed the amoeba
to speciFcally recognize food would have
been a great evolutionary progress. Such
a receptor could have been the ancestor
of a pattern-recognition receptor (PRRs).
Such PRRs have originally been proposed
by Janeway. They could serve in distin-
guishing bacteria or viruses, which carry
regularly organized membrane or coat
proteins named
pathogen-associated molec-
ular patterns
(PAMPs) from self-proteins,
which are not organized in such pat-
terns. In the meantime, equivalents of
PRRs have been found: the family of
Toll-like receptors (TLRs), which recognize
various types of viral or bacterial sub-
stances, such as lipopolysaccharide (LPS)
or dsRNA. And indeed, TLRs are expressed
on macrophages and on DCs.
All vertebrates and many invertebrates
have a population of phagocytic cells that
patrol their bodies. Macrophages are found
in higher vertebrates in especially large
numbers in connective tissue, in associa-
tion with the gastrointestinal tract, in the
lung, where they are found in both the
interstitium and the alveoli, along blood
vessels in the liver (termed
Kupffer cells
),
throughout the spleen, where they remove
senescent blood cells, and in the thymus,
where they aid in thymocyte education.
Beyond
that,
macrophages
are
also
found at several strategically important
locations in the lymph nodes. They are
particularly enriched in the marginal sinus
zones where the afferent lymph enters the
lymphoid tissue, and in the medulla, where
the efferent lymph collects before having
access to the blood. Here, they obviously
prevent antigens from entering the blood
stream, a critical event, as otherwise sepsis
would occur.
Irrespective
of
their
tissue
localiza-
tion, they differentiate from bone mar-
row–derived monocytes, which are con-
siderably
smaller
and
not
phagocyti-
cally active.
±or targeting macrophages into sites of
infection, macrophages bear low levels of
chemotactic receptors, such as the f-Met-
Leu-Phe or 7-transmembrane-
α
-helical re-
ceptor. It binds to N-formylated peptides
produced by bacteria, and rarely by mito-
chondria.
8.2
Antigen Recognition Receptors
Macrophages express several receptors
on
their
surface,
which
are
able
to
recognize a large variety of bacterial or
viral constituents (Table 5). The peculiarity
of some of these surface receptors is that
they can bind pathogen surfaces directly.
These receptors are also known as pattern-
recognition molecules, as discussed above.
Receptors of the innate immune system
mediate different functions. Several of the
Tab. 5
Antigen recognition receptors on
macrophages.
Receptor
Ligand(s)
Mannose receptor
(CD206)
Terminal mannose or
fucose of glycoprotiens
or lipids
Scavenger
receptor (CD36)
Anionic polymers on
microbial surfaces,
apoptotic bodies
f-Met-Leu-Phe
receptor
N-formylated peptides
TLR2
Peptidoglycans
Lipopeptides
TLR3
dsRNA
TLR4/CD14
Endotoxin (LPS)
TLR4/CD91
Hsps
TLR5
Bacterial flagellin
TLR9
CpG oligonucleotides
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