Antigen Presenting Cells (APCs)
Innate immunity
Acquired immunity
NK cells
B lymphocytes
Dendritic cells
T lymphocytes
Fig. 1
Cells of the innate immune system versus
cells of the acquired immune system. Eosinophils,
neutrophils, macrophages, and natural killer (NK)
cells confer innate immunity. B lymphocytes,
macrophages, and dendritic cells are professional
antigen presenting cells, often referred to as
‘‘APCs.’’ They are the key players in facilitating
acquired immunity.
eosinophils and neutrophils, and phago-
cytic cells, such as microglial cells in the
brain or Kupffer cells in the liver. None
of these elements require speciFc anti-
gen recognition. These cells belong to the
innate immune system. However, most
pathogens cannot be eliminated by in-
nate immunity alone but only through
the involvement of elements of the adap-
tive or acquired immune system, which
is antigen-speciFc. This system relies on
antigen presenting cells that do not simply
destroy antigens but expose their anti-
gens on the surface for recognition by
T cells. In particular, macrophages link
the innate with the acquired immune sys-
tem being both phagocytes and antigen
presenters. Antigen exposure to effec-
tor T lymphocytes leads to production
of antigen-speciFc antibodies, to cytolytic
elimination of infected cells in an antigen-
speciFc manner and/or to pathogen killing
by phagocytosis. Thus, antigen presenting
cells govern the initiation of both humoral
and cellular immunity.
Antigen Presenting Cells (APCs)
The Discovery of Langerhans
In the second half of the nineteenth cen-
tury, the histologist Langerhans was the
Frst to detect a cell that immunologists
nowadays call an
antigen presenting cell
He used a gold impregnation method to
stain skin sections and saw irregularly
shaped cells with long protrusions rem-
iniscent of dendrites of cutaneous nervous
system cells. These cells formed a net-
work of dendrites within the spinal layer
of the epidermis and were called
hans cells
(LCs). At the ultrastructural level,
LCs can be identiFed by unique organelles
in their cytoplasma, termed
Birbeck gran-
. Birbeck granules are unique to LCs
and allow us to distinguish them from
macrophages and other dendritic cells. Al-
most a century later, LCs were rediscovered
by immunologists and shown to function
as APCs. Today, it is obvious that LCs are
representatives of the dendritic cell fam-
ily, specialized in trapping antigens that
have penetrated the epidermis of the skin.
Hence, they function as the sentinels of the
antigen-speciFc skin immune response.
Professional APCs
The term APC refers to not only LCs but to
all types of leukocytes that are responsible
for taking up antigens at the entry sites of
the body, transporting them to lymphoid
organs where they recruit antigen-speciFc
T lymphocytes (short: T cells). APCs thus
act at the very beginning of an adaptive
immune response. In order to mount such
a response against an antigen that enters
the body for the Frst time, APCs must be
able to activate so-called
T cells that
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