362
Antigen Presenting Cells (APCs)
diacylglycerols, sphingolipids, and polyiso-
prenoids derived from endogenous and
microbial sources have been described
(Table 2).
Similar to pure lipids, only DNA or RNA
is widely unable to trigger generation of
antibodies. Moreover, APCs obviously lack
specialized receptors for DNA or RNA
necessary for activating T lymphocytes.
Nucleoproteins, however, are suitable to
generate anti-DNA antibodies. Thus, DNA
can serve as a hapten. Anti-DNA antibodies
are
actually
found
in
the
serum
of
patients suffering from the autoimmune
disease
systemic
lupus
erythematosus
(SLE). Some of these antibodies react with
denatured DNA, others with intact double-
strand DNA.
3.3
Origin of Antigens
Under normal circumstances, the im-
mune system relying on APCs reacts only
against foreign antigens, but not against
self-antigens. In cases in which a foreign
antigen is a homolog of a self-antigen, the
extent of the immune response decreases
with increasing similarity between both
antigens. To take this rule into account,
transplantation immunologists differenti-
ate between the donor and the recipient
of a transplanted organ: antigens derived
from a recipient of the same species are
called
alloantigens
. When the antigen is de-
rived from another species, it is named
xenoantigen
. In contrast to that,
autoanti-
gens
are derived from the same organism
and may cause autoimmune diseases.
4
Antigen Entry Sites
Vertebrates offer microbes a large interface
to
enter
the
body.
Consequently,
the
lymphatic system is organized in such
a way that lymphoid tissues are located
in close proximity to all putative entry
sites. Afferent lymphatic vessels drain
fluid and APCs from the skin and from
other peripheral tissues to the lymph
node. The spleen Flters antigen mainly
from the blood stream. The gut-associated
lymphoid tissues (GALT), which include
the tonsils, adenoids, appendix, and the
Peyer’s patches (PP) in the small intestine,
collect antigen from the epithelial surfaces
of the gastrointestinal tract.
Likewise, the bronchial-associated lym-
phoid tissues (BALT) and the mucosal-
associated lymphoid tissues (MALT) pro-
tect the respiratory epithelia and other mu-
cosa respectively. Each of these lymphatic
tissues traps foreign antigens through the
activity of migratory APCs that present
antigenic
peptides
to
T
lymphocytes,
thereby initiating antigen-speciFc immu-
nity. Importantly, even in the absence of
foreign antigen, lymphoid tissues provide
signals to lymphocytes via presentation of
self-antigens. This is important for the
survival of naive and silent T lymphocytes,
thereby contributing to the maintenance
of T-cell homeostasis.
4.1
APCs in the Skin
Antigen that has penetrated the epidermis
is
primarily
picked
up
by
LCs.
LCs
are derived from monocytes that leave
the blood stream and migrate into the
epidermis where they adopt the shape
of typical DCs. Antigen-fed LCs leave the
skin and migrate as so-called
veiled cells
via
the afferent lymph vessels to the draining
lymph nodes. There, they accumulate as
interdigitating dendritic cells (IDCs) in the
T cell–rich areas.
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