The importance of the innate immune response cannot be overstated. This is perha
ID: 267301 • Letter: T
Question
The importance of the innate immune response cannot be overstated. This is perhaps best demonstrated by examining a disease in which innate immunity is affected at both the first and second lines of defense and analyzing the consequences. Cystic fibrosis is a recessive genetic disorder which leads to changes in mucous secretions causing them to be very thick and viscous. Subsequent microbial infections of the respiratory system in these individuals can be devastating. The result of these infections is damage to many organs, most notably the lungs where scar tissue forms and eventually leads to lung failure if lung transplantation is not possible. Based on what you have learned about the innate immune response, please explain:
a. How a change in mucous viscosity might impact the ciliary escalator and the first line of defense
b. how thick mucus secretions (defect in the first line of defense) leads to an appropriate second line of defense
c. how this defect in the second line of defense culminates in lung damage. You also need to identify what the defect is in the second line of defense in your answer.
Explanation / Answer
a. ANS: Changes in the mucus viscosity have several impacts in cilia motility and in mucus clearance rates. Cilia movements in the respiratory tract maintain flow of mucus to an optimal rate, which thus permits optimal elasticity and viscosity. if the viscosity is low, the motility of the mucus will be greater and will overcome ciliary movement, and if the viscosity is too high, cilia are not able to transport it. So, deviations in the typical viscosity of the mucus, will have negative effects in ciliary movement and thus in the first line of defense.
As this case is increased viscosity, it means that mucus clearance and transport is not going to be possible, as ciliaryescalator can only transport mucus if it has an appropriate viscosity. Transport is important, as constant flow of mucus prevents or reduces the chances for bacteria and other pathogen colonization. As mucus movement is reduced, then the probability of colonization is increased. Increased viscosity of mucus also affects flow of substances secreted by epithelial cells, which may act as inhibitors of pathogen colonization and activity.
b. ANS: One of the issues in the specific case of cells on the second line of defense such as macrophages is that mucus provides a medium on which these cells can move. If the density of the mucus is too high, then these cells are not going to be able to move and attack pathogens and other bacteria properly, or their motility is going to be greatly reduced with the same negative effect. Even if the pathogens are not able to move either, colonization and multiplication of colonies is going to be greater. even if the macrophages are able to attack the pathogens, intracellular signaling proteins such as Interleukin family of proteins, won’t diffuse on the organs to activate the specific immune response
c. ANS: The second line of defence is a nonspecific resistance that destroys foreign pathogens in a generalied waywithout targeting any specific individuals. Inhibition of the mucus clearance and on the action of second line of defense elements such as macrophages, will cause increased rates of colonization of pathogens in the lung tissues as mentioned before. This will cause direct damage to the tissue as most products produced by pathogens are toxic for the cells in the tissues. So the inflammation can increase rate of lung damage.
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