Biomedical Engineering Reference
In-Depth Information
a proportion of the lymphocytes delivered to this tissue leave the circulating
blood by migrating out of veins that are lined by specialized high endothelial
cells. The B-cells that enter the lymphatic tissue in this way accumulate at
the edge of the lymphoid follicles and T cells in the tissue that surrounds
the follicles (57). Antigens picked up by dendritic cells located in the epithe-
lium and lamina propria, are processed as they are transported to regional
lymph nodes in the afferent lymphatics (Fig. 5C) and deposited in the mar-
ginal sinus of the node. These dendritic cells percolate through the node
where they have the opportunity to present antigen to both B cells located
at the edge of the follicles and T cells located in the paracortical tissues
between and beneath these follicles before they exit in the efferent lymphatic
of the node. The CD4 T lymphocytes that are activated by antigen presented
to them in paracortical tissue migrate to the edge of the follicles where their
chance of meeting a B cell that has been activated by the same antigen is
very much improved over that available in peripheral blood. The B cells that
receive help signals from the CD4 T cells proliferate and migrate into the
germinal center of the follicle where they produce antibody of varying affi-
nity that binds to antigen presented to them by a separate set of follicular
dendritic cells. The B cells that produce low affinity antibody receive a death
signal and undergo apoptosis whereas those that present high affinity anti-
body continue to mature into memory cells and plasma cells capable of
secreting antibody.
The bronchial associated lymphoid tissue (BALT) differs from that
found in regional lymph nodes in that it does not have a capsule and does
not receive afferent lymphatic vessels (compare Fig. 5C and D). The BALT
collections (Fig. 5D) receive antigen transported directly across the epithe-
lium by specialized epithelial M-cells. The cuff of lymphocytes that surround
the B cell rich germinal centers of these lymphoid follicles extends to the
epithelium of both the conducting airways and the alveolar surface suggest-
ing that they may receive antigens transported across both the alveolar and
small airway surface (36,41,57,59). The dominant class of antibody pro-
duced in a mucosal immune response is IgA and the major stimulus for
the switching of antibody isotype from IgM to IgA during this response is
TGF-b and IL-5 (57). The B cells that mature in the germinal centers of
the mucosal lymphatics home back to the lamina propria below the epithe-
lial basement membrane after they enter the circulation and secrete their
IgA as a dimer held together by a J chain. This complex binds to poly Ig
receptors at the base of the epithelial cells and is actively transported to
the airway luminal surface where it is released into the lumen by proteolytic
cleavage. Much remains to be learned about the mucosal immune response
of the lung in human disease and its precise relationship to the pathogenesis
of airway obstruction.
The humoral component of the adaptive immune response generates
mature B cells that produce antibodies that protect the host against
