Article on Immunologic Aspects of COPD

(If needed there are pictures provided in this article that can be utilized. They show a comparison
of a non smoker and smoker’s lung specimen, as well as figures for each step of the mechanism
of COPD in smokers.)

Prevalence

Affects about 10% of general population, and is prominent in heavy smokers with a high
prevalence of 50%. COPD is the fourth leading cause of death in developed countries mainly due
to tobacco smoking. Whereas, the risk factor of COPD in underdeveloped countries is burning
fuels for cooking/heating. COPD is projected to be the 3rd leading cause of death worldwide by
2020.

Feature of COPD

“COPD is a limitation of airflow that is not fully reversible and is associated with an
abnormal inflammatory response in the small airways and alveoli.” The main abnormality in the
airways is the inflammatory cell infiltration and remodeling that thickens the air space to
therefore reduce the airway diameter and increase resistance to flow. The majority of these
infiltrative cells are CD8+ T lymphocytes.

Mechanism of COPD in smokers

Findings such as inflammation in the lungs after cessation of smoking has suggested that there
may be an immune response, making COPD an autoimmune disease triggered by smoking. For
non-smokers with COPD may be associated with organ specific autoimmunity. This article
reviewed a possible mechanism that results in T cell mediated inflammation a cause of COPD.

Step 1-Initial response to Cigarette Smoke

It is unknown how smoking acts as a trigger to the innate immune response, but the
“danger hypothesis” of Matzinger is a plausible explanation. It is proposed that the cellular stress
or tissue damage from infection signals the immune system. This is done when the epithelium is
injured from foreign molecules from smoking that cause it to release ligands that bind to TLR
receptors (which recognize displayed pathogens). TLR’s then activate a nuclear factor that then
causes epithelial cells to make mediators of inflammation which activate macrophages and
neutrophils that then release proteolytic enzymes that damage lung tissue.

If the reaction in step 1 is reduced or controlled, this will not continue on to adaptive immunity
and the disease may stop here.
Step 2-T-Cell Activation and Proliferation

Mature dendritic cells go to lymph organs where co-stimulatory molecules and cytokines
create a specific T-cell antigen presentation and proliferation into CD4+ and CD8+ T cells.
These effector T cells express specific chemokine receptors that are strongly expressed in the
structural cells of the airways and pulmonary arteries in people with COPD.

Step 3-Adaptive Immunity Reaction

CD8+ T cells are prominent in airways of COPD patients, and this correlates with the
degree of severity in obstruction and emphysema. This suggests that they cause tissue injury in
COPD by releasing proteolytic enzyme to cause apoptosis or necrosis. B cells in lymphoid
follicles have also been found in airways of patients with COPD. These B cells have shown
mutations that have developed from a response to lung antigens. Pulmonary inflammation in
severe COPD includes large amounts of activated CD8+ T cells and B cells that persist even
after cessation to suggest a self-perpetuating process that is an aspect of autoimmune diseases.

Evidence of Autoimmunity in COPD

-Increased number of T cells and B cells.

-The presence of circulating antibodies against antigens in COPD.

-Presence of IgG auto-antibodies against pulmonary epithelium to promote cytotoxicity.

Why Some Smokers Evade COPD

Not all smokers have a reaction to the antigens that are released from damaged cells. It
was found that the lungs of people who smoke but have normal lung function have greater T
regulatory cells that prevent progression of the immune reaction. There is also a genetic
susceptibility factor found in a study of twins who smoke versus twins who don’t. However,
there no genes have been found to be related to autoimmunity directly.