Biomedical Engineering Reference
In-Depth Information
The physiological function of the immune system (inflammation) is
defense against infectious microbes. However, even noninfectious foreign
substances can elicit immune responses. Furthermore, mechanisms that nor-
mally protect individuals from infection and eliminate foreign substances
are, in some situations, capable of causing tissue injury and disease. There-
fore, a more inclusive definition of immunity is a reaction to foreign
substances, including microbes, as well as to macromolecules, such as pro-
teins and polysaccharides and other agents regardless of the physiological
or pathological consequences of such a reaction (10).
It is important for the understanding of the immune reaction to cigar-
ette-smoke exposure, to realize that innate and adaptive immune responses
(which involve T-cells) are components of an integrated system of host
defense in which numerous cells and molecules function co-operatively.
Two important links exist between innate immunity and adaptive immunity.
First, the innate immune response to microbes (or other offending mole-
cules) stimulates adaptive immune responses and influences their nature.
Second, adaptive immune responses use many of the effector mechanisms
of innate immunity to eliminate microbes or other antigenic substances,
and they often function by enhancing antimicrobial activities of the defense
mechanisms of innate immunity (10).
It is not possible, therefore, to write about the role of the adaptive
immunity (T-lymphocytes in COPD), without reviewing some of the fea-
tures of the innate inflammatory responses induced by cigarette-smoke
exposure, as the innate immune response will determine the development
of the adaptive immune response involving CD4
þ
and CD8
þ
T-cells, as
it is seen in COPD.
B.
Innate Immune Reaction in COPD
The innate immune system consists of epithelial barriers, circulating cells
[macrophages, neutrophils, eosinophils, mast cells, NK cells,
gd
T-cells,
and dendritic cells (DCs)], and proteins (complement) that recognize micro-
bes or substances produced by infections or other foreign harmful sub-
stances and initiate responses that eliminate the offending agent (10). It
has been designed primarily to fight against offending micro-organisms,
and most of the studies leading to the understanding of this complex system
have been based on experiments involving micro-organisms and their pro-
ducts. However, cigarette smoke and other nonmicrobial pollutants (ozone,
NO
2
, and diesel fumes among others) produce a clear innate immune inflam-
mation that is not driven by an infecting organism. Acute innate immune
reactions in the lung can be seen after 24 hr of exposure to two cigarettes
in mice (11) or after 6 hr of acid instillation into the trachea (12).
How does the respiratory system mount a reaction, designed as far as
we know to fight microbial products, against cigarette smoke? As proposed
