Biomedical Engineering Reference
In-Depth Information
microbes that remain in the extracellular space (57). These antibodies are
able to neutralize microbial toxins and initiate a much more efficient opso-
nization and phagocytic process that can be mounted by the innate system.
Antibodies that attach to the surface of microorganisms also bind the C1q
component of the large multimeric C1 complement molecule circulating in
the plasma and initiating the classical complement pathway. Interleukin 2
is produced by T lymphocytes and stimulates the proliferation of T cells,
B cells, and natural killer cells. A Th2 subset of CD4 positive lymphocytes
secrete IL-4 to initiate antibody isotype switching to IgE production in B
cells and IL-5 that stimulates eosinophil production and activation. IL-5
also co-operates with TGF-
b
to switch B cells to the production of an
IgA antibody isotype. Without these stimuli the B cells produce the more
common IgM, IgG, and its subclasses.
The cellular component of the adaptive immune response protects the
host from microbes that either survive within phagocytes or infect nonpha-
gocytic cells (58). The adaptive immune response to microbes residing within
the phagosomes of phagocytes is mediated by a CD4 Th1 lymphocytes as
well as CD8 T cells. Both these cells are able to recognize antigens displayed
on the surface of macrophages and secrete cytokines that activate them to
kill the organisms they have phagocytosed. The CD8 positive lymphocytes
are also able to recognize nonphagocytic cells infected by intracellular
pathogens and destroy them in three steps. The first is a recognition step
where the cytotoxic lymphocyte uses the T-cell receptor to bind to foreign
material displayed on the surface of the target cell with the HLA self mole-
cule. The second involves the molecule perforin which creates holes that
connect the cytotoxic T cell to its target and the third involves the introduc-
tion of the enzyme granzyme that activates the target cell caspases and
introduces apoptosis.
There is a substantial increase in mucosal lymphoid follicles in the small
airways of patients with severe (GOLD-3) and very severe (GOLD-4) COPD
(36). This probably reflects an adaptive immune response to the colonization
of the peripheral lung in the later stages of COPD severity. The bacteria that
commonly colonize and infect the lungs of patients at this stage of their
disease include Haemophilus influenzae, Moraxella catarrhalis, Streptococcus
pneumoniae, Pseudomonas aeruginosa, Enterobacteriaceae, and Haemophilus
parainfluenzae (43). Sethi and colleagues have reported an important longitu-
dinal cohort study of patients with COPD that was designed to detect new
strains of organisms by pulse field electrophoresis (60). Their results showed
that the presence of new strains is common, that some new strains produce
exacerbations and that the acquisition of a new strain enhances the risk of
an acute episode more than twofold. Abbe Abe (61) and others have also
shown that the cellular immune response to these new strains is type specific
and that it commonly targets epitopes expressed on the outer membrane
proteins (OMPs) of the organism. The antibodies produced against one
