Biomedical Engineering Reference
In-Depth Information
cigarette smokers have increased numbers of total cells and macrophages,
but no neutrophils, while older smokers have increased numbers of both
neutrophils and alveolar macrophages in the BAL, when compared with
nonsmokers. From these data, originated the concept that the inflammatory
reaction in the lungs of smokers consisted of neutrophils and macrophages.
The connection between neutrophils and elastase, macrophages and
proteinases, and the destruction of lung tissue by these cells and their potent
proteinases was promptly made, and the proteinase-antiproteinase
balance became the paradigm for the pathogenesis of COPD for over 40
years.
Most likely, there is an important link between the inflammatory
cells, their proteinases, and the injury in smokers' lungs but, clearly, there
are other inflammatory events not necessarily related to the proteinases
that could be important and need to be explored. For the last 10 years,
the investigation of the possible role of inflammation in the pathogenesis
of COPD has switched to the T-cells after Finkelstein et al. (7) described
a prominent T-cell infiltration in the lungs of patients with COPD that was
strongly related to the extent of emphysema. Subsequent work by other
authors (see later) confirmed these results and showed that the
T-cells in the lung of these patients were predominantly CD8
þ
T-cells.
These findings introduced possible new mechanisms for the pathogenesis
of COPD and prompted us to suggest that, if T-cells were involved,
COPD might be an autoimmune disease triggered by cigarette smoking
(8,9).
The aim of this chapter is to review our present knowledge of T-cells
in COPD, explore how they, through an adaptive immune inflammation
(autoimmunity?), could act in the development of the disease, and to explain
how the old and new paradigms could work together in the development of
COPD.
II.
INNATE IMMUNITY
A.
Innate and Adaptive Immunity
The concept of inflammation has evolved substantially since the important
observations made by Hunninghake and Crystal (5) and Martin et al. (6),
and has been fully incorporated into the immunologist's domain. It is
now recognized that an ''early inflammatory'' reaction—neutrophils,
macrophages—represents the so-called innate immune reaction, a primitive
function already found in prokaryotic beings (fruit fly). Intimately linked
with the innate immunity, and only present in eukaryotic animals, is the
adaptive immune response involving B- and T-cells. We should interpret
the traditional inflammation in smokers—neutrophils, macrophages—as
the innate immune response to cigarettes that, as we will see, could lead
to an adaptive response with T-cells.
