Carbohydrate Antigens
293
responsible for the initial recognition step
in the Frst line of internal defense, which
triggers the initiation of various pathogen-
killing or inhibition machineries. These in-
clude agglutination, endocytosis by phago-
cytic cells, and the activation of protease
cascades, resulting in clotting, melaniza-
tion, or complement-mediated killing of
the pathogen. A fucose binding lectin,
called
fucolectin
, was demonstrated to be
an immune-recognition molecule in in-
vertebranes and vertebrates, such as the
horseshoe crab (
Tachypleus tridentatus
)and
the Japanese eel (
Anguilla japonica
).
5
Immune Responses to Microbial
Polysaccharides
5.1
T-independency of Anti-polysaccharide
Responses
Microbial
polysaccharides
are
T-inde-
pendent antigens. As illustrated in ┬▒ig. 7,
a polysaccharide activates B-cells directly
by cross-linking their membrane-bound
immunoglobulins, the B-cell antigen re-
ceptors (BCRs). Cross-linking BCRs is
sufFcient to induce B-cell proliferation,
CD40L
FasL
Fas
mlg
MHC II
T cell
B-cell
(a) T-independent
(b) T-dependent
Tl-2
Tl-1
B-cell
Fig. 7
Schematics of the TI- and TD-models of B-cell activations. The
diagram demonstrates two distinct models of B-cell activation, the
T-independent (TI) and the T-dependent (TD) models. (a) Both TI-I
antigen (LPS) and TI-II antigen (polysaccharide) are able to cross-link
the BCR (Ig) of B-cells and induce B-cell proliferation in the absence of
T-cell help. TI-1 antigens (LPS) are po
lyc
lona
lB-ce
l
lact
ivators;TI-II
antigens activate only the B-cells that express antibodies speciFc for
given TI-II antigens. (b) TD protein activates B-cells in an
antigen-speciFc and MHC-restricted manner. Unlike the TI antigens,
protein antigens, in general, do not contain repeating structures and
thereby are unable to cross-link the BCR (Ig) of B-cells on their own.
Instead, specialized antigen-presenting cells, such as dendritic cells,
macrophages, or B-cells themselves, take up protein antigens, process
them in cells, and present the protein-derived peptides by their MHC
class II molecule. Such peptide-bound MHC class II molecules are able
to bind and activate CD4
+
T-helper cells (Th) that express the
appropriate T-cell receptor (TCR). Subsequent to the Frst initiation,
additional molecular interactions, such as CD40 and CD40 ligand, and
CD28/CTLA4-Ig with B7-1/B7-2, take place and activate further the
interaction between T-B cells.
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