T-Lymphocytes - Chronic Obstructive Pulmonary Disease - page 212

(49). Apoptotic cells and = or their products are normally handled by antigen-
presenting cells (APCs) and can act as antigens and stimulate an adaptive
immune reaction mediated by the major histocompatibility complex
(MHC) Class I molecules and priming CD8 þ T-cells (see later). Increased
apoptosis in emphysema in humans has been well documented (8).
Another direct consequence of exposure to cigarette smoke is necrosis
of epithelial and endothelial cells. After exposure to tobacco smoke in vitro,
a 38% reduction of the cell population in culture can be observed (18) prob-
ably as a result of necrosis. This was confirmed by a recent report showing
that necrosis of epithelial and endothelial cells resulted after exposure to
cigarette smoke condensates, probably as an effect of oxidative stress (52).
Cellular necrosis releases the cytoplasmic contents, including the peptide fin-
gerprint of the cell (including the antigenic fingerprint), and heat shock pro-
teins (HSPs). The HSPs chaperone these peptides for presentation to DCs,
where they are cross-presented to MHC Class I molecules and could activate
CD8 þ T-lymphocytes (see below).
An important requirement for the initiation of a successful adaptive
immune reaction is the prevalence, and persistence, together with the dose
response of the offending agent. In cigarette smoking, the insult prevails
daily and persists for years largely predisposing to a high prevalence of dis-
ease.

It can be seen that the innate immune response, elicited by exposure to
cigarette smoke, could produce a considerable amount of potential antigenic
material (peptides, apoptotic, and necrotic debris) that ought to follow the
rules set for the full immune reaction; i.e., innate immunity is followed by
adaptive immunity, when it cannot handle the ''pathogens'' on its own.
The difference between pathogens, the original reason for the evolution of
the immune response, and exposure to pollutants (cigarette smoke, ozone,
etc.) is that after pollutants trigger the innate immune reaction, the innate
reaction itself becomes harmful, injures the lung, and has the potential to
trigger an autoimmune reaction by ''successfully'' engaging the adaptive
immune response. It would seem that the ability to suppress the develop-
ment of an adaptive immune response would arrest this chain of events
and could prevent the development of COPD (Fig. 2).

III. ADAPTIVE IMMUNITY

A. Dendritic Cells

We have seen that innate immunity specifically recognizes conserved mole-
cules from pathogens, or danger signals from cells, through a family of
receptors. This recognition by the immune system has two major effects.
First, it triggers effector cells of inflammation, neutrophils, macrophages,
and other cells, which represent an immediate defense at the sites of