Chronic peripheral airways (non-cartilaginous airways) there is an

Chronic obstructive
pulmonary disease is a progressive disease characterised by airflow obstruction
and destruction of lung parenchyma (cellular tissue of the organ). The airway
limitation becomes progressive and is associated with an abnormal inflammatory
response of the lungs to noxious particles of gas, primarily caused by
cigarette smoking.

All cigarette smokers
have inflammatory changes in their lungs however patients with COPD have
enhanced or abnormal inflammatory response to inhaled toxic agents. Reactions
to these inhaled toxins could result in mucous hypersecretion 1(chronic
bronchitis), tissue destruction (emphysema), disruption of normal repair and
defence mechanisms causing small airway inflammation (bronchiolitis) and
fibrosis.

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Structures of lungs effected by immune response

The pattern of inflammation involves recruitment of lymphocytes,
macrophages and neutrophils, as well as activation and damage to structural
cells following the release of inflammatory chemokines and cytokines. The
pathological changes in the lungs of patients with COPD are found in the
proximal and peripheral airways, lung parenchyma and pulmonary vasculature.
These changes are present to different extents in affected individuals.

Proximal airways have an increase of macrophages and CD8
T-lymphocytes (virus, bacteria and tumor surveillance). These T lymphocytes
secret cytokines like TNF-a that causes apoptotic cell death (resulting in
inflammation). Submucosal bronchial gland enlargement occurs and goblet cell
metaplasia (resulting in excessive mucous production or chronic bronchitis)

Moving down to peripheral airways (non-cartilaginous airways) there
is an increased number of B-lymphocytes, lymphoid follicles and fibroblasts. Peribronchial
fibrosis airway narrowing occurs as COPD progresses with age.

Lung parenchyma has alveolar wall destruction due to loss of
epithelia and endothelial cells. These injured epithelial cells produce MIG and
IP-10 that are ligands for CXCR3 expressed on Th1 cells2.
Th1 cells are required in producing elastin-destroying enzyme that causes
emphysema that causes exacerbation of COPD. 

Innate response

The immune
inflammatory changes associated to COPD are linked to a tissue-repair and
-remodelling process that increases mucus production and causes emphysematous
(irreversible expansion of alveoli) destruction of the gas-exchanging surface
of the lung

Innate inflammatory
system is the first line of defence where the muscociliary clearance occurs
consisting mainly of macrophages that clear foreign material from lower
respiratory tracks. In COPD patients this function is impaired making them
prone to infection in respiratory tracts due to accumulation of foreign
substances.

Alveolar macrophages
clear airspaces of infections by secreting of oxygen metabolites, lysozyme,
antimicrobial peptides and proteases, and through processes of phagocytosis and
intracellular killing3.
However, this function is impaired in COPD patients thus making them more likely
to have lung infections.

Cigarette smoking
activates innate immune cells by triggering pattern recognition receptors to
release “danger signal” that act as ligands to Toll-like receptors,
triggering the production of cytokines and inducing innate inflammation.

Complement system4
binds to a multitude of foreign surfaces and trigger clearance through
phagocytosis. These proteins and phagocytic cells have receptors for them and
are very important to be maintained in a smoker’s lung. However large
quantities of carbonaceous combustion products strain the clearance ability of
alveolar macrophages.

Adaptive Immune response

COPD is characterised
when there is an increase in inflammatory cells like neutrophils, macrophages,
T Lymphocytes (CD8 > CD4) and dendritic cells. These
cells release cytokines, chemokines, reactive oxygen species and proteolytic enzymes.
Growth factors such as transforming growth factor-? (TGF-?) which may cause
fibrosis in the airways either directly or through the release of another
cytokine (connective tissue growth factor)

Mature lymphoid follicles are shown to be increased in airways of
COPD patients. Their presence is associated due with bacterial colonization or
frequent lower respiratory tract infections or possibly an autoimmune response.
These mature follicles mature5
to plasma cells producing antibodies (in response to antigens like bacteria,
toxins) that promote mucosal immunity (IgA) that would increase pathogen
clearance. Binding of antibodies causes complement activation, their action
results in air space enlargement

 

 

Oxidative stress

Oxidative stress is the imbalance of oxidants (free radicals) and
antioxidants and this burden is increased in COPD and could further progress in
exacerbations. This causes inactivation of antiproteinases (doesn’t allow
protein digestion) and stimulation of mucous production. Oxidative stress6
could induce inflammatory responses by activating many intercellular pathways-
enhancing transcription factor activation (e.g.nuclear factor-?B (NF-?B)) and
epigenetic events (such as decreasing histone deacetylates) that lead to
increased gene expression of proinflammatory mediators. They also cause DNA
damage that could further lead to diseases such as Cancer, neurodegenerative disorders
and atherosclerosis.

Conclusion

COPD patients have exaggerated inflammatory andimmune response due
to the exposure of various injuries (caused from cigarette smoking).  The cycle of inflammation and repair may
result in resolution thus associating with mucous hypersecretion, fibrosis, tissue
destruction and both airway and parenchyme remodeling. Picture7
below shows the basic summary of the actions of immune system cells that act on
the respiratory tract in COPD patients

1 ABCD of COPD pg6-7 –
4/11/2010  by Graeme P.Currie

2 http://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.0010025
– 19/10/2004 Public Library of Science.

3 http://www.atsjournals.org/doi/full/10.1164/rccm.2210007
– 15/1/2003 by Heffrey B.Rubins

4 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2713325/
– November,2005 by Robert P.Schleimer

5 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5142126/figure/F1/
– August 2016, by Francesca Polverino (American physiological society)

6 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3546726/
– December,2012 by Eirini Neofytou

7 http://www.thinkcopdifferently.com/en/About-COPD/What-is-COPD/Pathophysiology-of-COPD
, Nature review immunology, pg 183 2008- Barnes, PJ

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