Question

Individuals who actively smoke have a much higher rate of lung infection. Explain which first-line defense mechanism may be impaired by smoking which allows pathogens to more readily enter the lower respiratory tract.

Answer 1

Smoking increases the susceptibility to
pulmonary infection and is a risk factor for the
development of chronic obstructive pulmonary disease(COPD).

It is postulated that cigarette smoke suppresses the activation of the innate immune system in response to bacterial infection.

In the central airways the epithelial lining is ciliated and covered with a protective mucus layer able to transport particles and microorganisms away from the central airways by mucociliary clearance. This epithelial barrier constitutes the first line of defence. Interspersed between the epithelial cells, mucosal T-cells are located as a specific defence against infectious agents that are penetrating the mucosal barrier. Further into the tissue, in the lamina propria, macrophages, neutrophils and T-cells provide both innate and adaptive immune responses to help clear infections. In the lower respiratory tract, alveolar macrophages are the key cells to keep the environment sterile with the help from, among others, T-cells.

The ciliated respiratory epithelium, the main target of most respiratory viruses, is the first line of defense against harmful environmental agents and protects by sweeping particles away in the overlying mucus gel layer, phagocytosing and killing some pathogens, maintaining a barrier through tight junctions and priming, activating and recruiting other immune cells. Cigarette smoke and many of its components produce structural changes in the respiratory tract. These changes include peribronchiolar inflammation and fibrosis, increased mucosal permeability, impairment of the mucociliary clearance, changes in pathogen adherence, and disruption of the respiratory epithelium .These changes are thought to predispose to the development of upper and lower respiratory tract infections, which may amplify the cigarette smoke–induced lung inflammation. A number of components of cigarette smoke, including acrolein, acetaldehyde, formaldehyde, free radicals produced from chemical reactions within the cigarette smoke, and nitric oxide, may contribute to the observed structural alterations in the airway epithelial cells.

Smoke directly compromises the integrity of this physical barrier, increases the permeability of the respiratory epithelium and impairs mucociliary clearances. Although cigarette smoke has been shown to activate epithelial cells to produce pro-inflammatory mediator, it attenuates the in vitro production of pro-inflammatory mediators by epithelial cells following stimulation with pathogen-associated molecular patterns (PAMPs), such as lipopolysaccharide or double-stranded RNA . Smoke also induces direct oxidative damage to membrane lipids and causes extensive single-strand DNA breaks, triggering repair and apoptotic cascades .Thus, cigarette smoke acutely suppresses the respiratory epithelium and chronically can cause damage, inflammation and may ultimately transform it.

The innate host defence system of the lung is a first-lineprotection system.

Antimicrobial peptides(AMPs) are important effector molecules of the iinnateimmune system.

Thedefensins andcathelicidins are the principal families of AMPshat are expressed in the respiratory tract.

The b-defensins are mainly produced by epithelial cells and are secreted onto the airway surface where they have a broad spectrum of antimicrobial activity.

. In vitro studies and clinical studies show
that the expression of several AMPs is induced by bacterial products and inflammatory mediators.

cigarette smoke suppresses the activation of the epithelial innate host defence system of the lung. Oxidative stress appears to play a role
because hydrogen peroxide exposure mimics the suppressive effect of cigarette smoke and antioxidant treatment weakens this effect.

Cigarette smoke is known to inhibit
the function of professional immune and host defence cells such as dendritic cells,25 T cells26 and alveolar macrophages.