Question

People who smoke have higher rates of respiratory infections. Explain using 150-200 words, why this might be, involving aspects of the first line of defense.

Answer 1

cigarette smoking also appears to be a major risk factor for respiratory tract infections... Both active and passive cigarette smoke exposure increase the risk of infections. Passive exposure to tobacco smoke in children contributes significantly to morbidity and mortality... The mechanism of increased susceptibility to infections in smokers is multifactorial and includes alteration of the structural and immunologic host defenses.

Structural changes caused by smoking

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 clearance . Although cigarette smoke has been shown to activate epithelial cells to produce pro-inflammatory mediators )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....

Similar to its effects on the respiratory epithelium, cigarette smoke compromises the ability of alveolar macrophages to phagocytose bacteria ) and apoptotic cells and to sense PAMPs...

Natural killer (NK) cell activity in peripheral blood has been reported to be reduced in smokers compared with nonsmokers . These alterations appear to be reversible, since NK activity in ex-smokers was similar to that of a never-smoking group compared with smokers . The recovery period was relatively short, as little as 6 weeks . Since NK cells are important in the early surveillance response against viral infections and resistance against microbial infections , impairment of NK cell activity by cigarette smoking is a potential mechanism for the increased incidence of infections among smokers.

natural killer cells have an important role in innate host defense against microbial agents and in protective antitumour immune surveillance. This is achieved by direct cytotoxicity through perforin and granzymes, CD95 ligand-induced apoptosis and pro-inflammatory cytokine and chemokine release . Several studies have shown that NK cell numbers and activity are decreased in smokers compared with non-smokers . Exposure to cigarette smoke attenuates the cytotoxic activity and cytokine production of NK cells in humans and mice , thereby linking NK cell defects to increased infection risk and cancer.

Animal studies have shown that nicotine inhibits the antibody-forming cell response through impairment of antigen-mediated signalling in T cells and suppression of intracellular calcium response ). It has been suggested that nicotine through activation of protein tyrosine kinases and depletion of inositol-1,4,5-trisphosphate-sensitive calcium stores in T cells could be a major immunosuppressive component in cigarette smoking.....