Biomedical Engineering Reference
In-Depth Information
The TNF-a will also induce production of vasodilatory substances (VEGF,
postacyclin) and coagulation factors that would facilitate the entry of
leukocytes to the site of injury (10).
One of the main functions of the effector Th-1 T-cells (and Tc-1) is the
activation of alveolar macrophages. This is mediated by IFN-g and the
expression of CD40 ligand, CD40L, will engage CD40 in macrophages that
are presenting antigens to the T-cells. Once activated, macrophages will
increase production of reactive oxygen intermediates, nitric oxide, and lyso-
somal enzymes and will increase secretion of many cytokines, TNF-a, IL-1,
IL-2, IL-18 among others (10). Activated macrophages are aimed at the
more efficient killing of organisms and promote further inflammation
mainly by TNF-a, IL-1, and short-lived lipid mediators.
Activated macrophages can also induce the formation of repair tissue
by secreting growth factors that stimulate fibroblasts proliferation (plate-
let-derived growth factor), collagen synthesis (TGF-b), and new vessel for-
mation. In addition to their effector functions, activated macrophages
become more efficient APCs by increasing the MHC Class II expression
and stimulation of T-cell proliferation and differentiation such as IL-12
and IL-18 (10).
It can be seen that the inflammatory process leading to disease in
COPD cannot be focused in one single cell. Each cell would have their role,
or roles, to play in the process, but there is a necessary and important
co-operation among all the cells involved and this can be best orchestrated
by the T-cells, as we have seen. The rest of the inflammatory cells, besides
being effector arms under the direction of the T-cells, enhance and maintain
the T-cell function by providing the necessary inflammatory milieu for the
maintenance of T-cell activation and costimulation.
A complex inflammatory process is a perfectly designed instrument to
fight infection that has gone wrong producing disease; a link of events well
described in autoimmune diseases, and most likely operating in COPD.
VI.
WHY ONLY SOME SMOKERS DEVELOP COPD: THE
IMMUNOLOGICAL PARADIGM
We have, so far, reviewed the potential role that T-lymphocytes could play
in the development of COPD, and how the increase of T-cells in the lungs of
smokers could be prompted by the presence of antigenic peptides: self or
modified self-antigens, in the lung. This proposed new paradigm for the
pathogenesis of COPD, autoimmunity, could also explain why only a rela-
tively small proportion of smokers develop COPD, a fact that the protei-
nase-antiproteinase paradigm could not easily explain.
We could assume that all smokers would initially develop airway and
parenchymal inflammation, an innate immune response, with tissue damage
