Antigen Presenting Cells (APCs)
375
small molecules, such as the TCR and
MHC molecules, from interacting with
each other.
Exploratory adhesive interactions of T
cells and APCs precede formation of the
synapse. The adhesion molecule ICAM-3
has been reported to initiate antigen-
independent scanning of the APC surface
by T cells followed by early signaling
events
and
rearrangements
of
the
T
cellular cytoskeleton. The synapse itself
appears to be a highly dynamic structure.
At the beginning, cognate TCR ligands
localize
to
an
outermost
ring
of
the
nascent
synapse,
whereas
LFA-1
and
ICAM-1 constitute the c-SMAC. After 5
to 10 min, ICAM-1 moves to the p-SMAC
and MHC-peptide clusters concentrate at
the heart of the synapse. Finally, the
coreceptor CD4 progressively migrates out
of the c-SMAC in the course of synapse
maturation. Strikingly, synapses between
naive CD4
+
or CD8
+
TcellsandDCscan
form in the absence of antigen or MHC
molecules. This ±nding underscores the
fact that the synapse is a flexible rather
than a static entity. In conclusion, the
immunological synapse can be viewed
as a platform that favors interactions
between costimulatory molecules, such as
CD28, thereby facilitating priming of naive
T cells.
8
Macrophages
Macrophages belong to the ±rst line of in-
nate defense to protect the vertebrate body
from invasive microorganisms. When a
microorganism crosses an epithelial bar-
rier and replicates in a host tissue, it is
rapidly recognized by mononuclear phago-
cytes, or macrophages. Macrophages dif-
ferentiate from monocytes that leave the
blood circulation to migrate into tissues
throughout the body. Together with neu-
trophils, macrophages are key players of
the innate immune response because they
are equipped to recognize, ingest, and
destroy many pathogens without the aid
of an adaptive immune response. It is
noteworthy that macrophages endocytose
the equivalent of their entire cell vol-
ume in about 30 min and, on the other
hand, secrete more distinct products than
even hepatocytes, which secrete numerous
serum proteins.
As macrophages react very rapidly on en-
countering an infecting microorganism,
and since the immune system of inver-
tebrates relies entirely on macrophage-
driven innate responses, in the early 1960s,
Elie Metchnikoff believed that the same
would be true for vertebrates. In the mean-
time, we know that macrophages are of
superior importance in the nonadaptive
branch of our immune system, but play a
less dominant role in mounting an adap-
tive immune response, since they express
comparably low amounts of MHC and cos-
timulatory molecules. Nevertheless, they
do cross talk extensively with B and T cells
and may be very important for targeted
effector T-cell functions in the context of
infected cells.
8.1
Evolutionary and Cellular Origin
Macrophages in culture behave very simi-
lar to amoeba feeding on microorganisms.
From this and other similarities, it was
concluded that the amoeba is one of the
earliest or the earliest form of a phago-
cytic cell or macrophage. The evolutionary
pathway from the ancient amoeba to the
modern macrophage is unknown. How-
ever, the urgent need for an amoeba to
distinguish between other amoeba that
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