Pulminary defence mechanisms

Question 1

Why are the lungs a potential site of immunological vulnerability?

Answer 1

• Fast movement of air in and out of the lungs - this places limits on the level of filtering/barrier structures possible (e.g. the solution the GI tract uses – stomach acid – is not possible).
• Efficient gas exchange - requires a large surface area, a thin membrane at the gas-blood interface (delicate structures vulnerable to damage and infection)
• Innervation by blood vessels, and a warm, moist environment - to allow diffusion of respiratory gases (but in which microorganisms also thrive).

Question 2

Give examples of particles/organisms that may be breathed in and could cause harm.

Answer 2

• Microorganisms – bacteria, viruses, fungi, helminths
• Allergens – dust, pollen
• Organic particles – occupational exposures, pollution (e.g. diesel particulate matter)
• Toxic gases – carbon monoxide, sulphur dioxide, nitrogen dioxide

Question 3

Give examples of larger particulates that can end up in the respiratory system.

Answer 3

Foreign body aspiration (e.g. food, liquid, choke hazards)

Question 4

Give examples of fine particulates that can end up in the respiratory system.

Answer 4

o	Pollution (<2.5 - 1000 μm, depending on the specific particle/source. Nanoparticles from diesel exhausts appear to be particularly damaging to the respiratory system as they are able to reach lower parts of the respiratory tree due to their small size)
o	Dust (0.1-1000 μm)
o	Pollen (10 - 100 μm)

Question 5

Give examples of microscopic pathogens that can end up in the respiratory system.

Answer 5

o Fungal spores
o Bacteria
o Viruses

Question 6

What physical defences to foreign objects does the respiratory system have?

Answer 6

• Large scale = nasal hairs, nasal turbinates, branching airway structure.
• Micro scale = cilia, mucus

Question 7

What protective reflexes does the respiratory system have?

Answer 7

coughing, sneezing, expiratory reflex

Question 8

What is featured in the immunological defence system of the respiratory system?

Answer 8

• Lung resident immune cells (e.g. alveolar macrophages)
• Structural cells (epithelial cells)/innate immunity
• Antimicrobial proteins

Question 9

What are nasal turbinates and their function?

Answer 9

Mucous membrane-lined, ridged structures within the nasal cavity that help to warm and humidify air before it reaches the airways/lungs, as well as help to filter out particles larger than ≈ 2μm.

Question 10

What is mucus produced by and what is their function?

Answer 10

Produced by submucosal glands (90%) and goblet cells (10%), which traps inhaled particles.

Question 11

What does mucus consist of?

Answer 11

a gel with elastic and viscous properties, which consists of 97% water and 3% solids (mucin, other proteins, salts, lipids), and also contains lysozyme and various antimicrobial proteins to destroy trapped microorganisms.

Question 12

Where does the mucus gel layer lie?

Answer 12

On top of a periciliary layer (≈ 7μm deep) which provides a media of low viscosity in which cilia can beat.

Question 13

What is the role of the cilia?

Answer 13

the respiratory tract is lined by ciliated epithelium, the coordinated beating of cilia produces a wave of movement that propels the mucus gel layer (and any trapped particles) towards the pharynx, where it is then swallowed or expelled.

Question 14

How do the cilia work?

Answer 14

Each individual cilia moves backward and forwards, the cilia only contacts the mucus gel layer during the forward stroke, as the cilia bends during the reverse stroke so that its tip passes beneath the mucus layer. Thus, the gel layer is propelled in one direction.

Question 15

What is the difference between healthy and infected mucus?

Answer 15

Healthy - clear/slightly cloudy and easily cleared
Infected - mucus may turn yellow or green following respiratory infection due the presence and breakdown of granulocytes. Airway pathology can also result in changes to mucus viscosity, either due to breakdown/shedding of surrounding epithelium or mucus dehydration/poor clearance (e.g. cystic fibrosis).

Question 16

What is the level of mucus production modulated by?

Answer 16

Parasympathetic nervous system stimulation (via cholinergic activation of submucosal glands) as well as local inflammation (e.g. respiratory infection or during an asthma attack).

Question 17

In what diseases is mucociliary impaired and what effect does it have?

Answer 17

In both cystic fibrosis and chronic bronchitis, mucus clearance is impaired leading to recurrent respiratory infections and resulting inflammation/tissue damage.

Question 18

What is the basic mechanism common to both protective reflexes?

Answer 18

activation of afferent sensory neurons, which transmit the impulse to breathing centres within the brain (i.e. the medulla, located within the brainstem). Efferent signals are then transmitted to specific respiratory muscles (e.g. the diaphragm, intercostal and abdominal muscles), the glottis (i.e. to close/open the windpipe) and airways to initiate a coordinated respiratory effort which rapidly expels air from the nasal cavity/airways/lungs.

Question 19

What is the mechanism involved in sneezing?

Answer 19

It is initiated by stimulation of sensory receptors within the nasal cavity and involves a deep inspiration phase, a compression phase (during which the glottis is closed, leading to pressure build-up), and a final expiration phase in which air is expelled.

Question 20

What is the mechanism involved in coughing?

Answer 20

triggered by stimulation of receptors within the larynx and large airways. In contrast to sneezing, coughing can also be initiated voluntarily, and involves bronchoconstriction to further increase expulsion pressure.

Question 21

What is the laryngeal reflex?

Answer 21

A short, forcible expiratory effort without a preceding inspiration (differentiating it from coughing), triggered by stimulation of sensory receptors within the vocal folds.

Question 22

What is the function of the laryngeal reflex?

Answer 22

Prevent foreign bodies entering the airways, and to expel phlegm from the upper respiratory tract.

Question 23

What is the function of branching?

Answer 23

Acts to increase filtering of air and prevent particles from reaching lower respiratory structures.

Question 24

How does the effect of branching work?

Answer 24

When inhaled air reaches an airway branching site, airflow changes from laminar to semi-turbulent flow pattern, increasing particle deposition as more particles come into contact with the mucus-lined airway wall.

Question 25

What are alveolar macrophages (AM)?

Answer 25

The resident phagocytes within the lung and develop from progenitors produced in the bone marrow that migrate to the lung.

Question 26

Where is the function of AMs?

Answer 26

Are found within the airspace (and can travel between alveoli) and phagocytose pathogens, foreign material and cell debris, digesting it into residual material that is subsequently removed by the lymphatic system.
In general they prevent respiratory infections.

Question 27

What is meant by lung micrbiota?

Answer 27

The mucosal surfaces of the respiratory system are not sterile (even in healthy individuals) – they are colonised by huge numbers of commensal bacteria.

Question 28

What is the role of lung microbiota?

Answer 28

The commensal bacteria living in the walls of the respiratory system seem to play important roles in resisting infection by other pathogens and the development/modulation of a healthy immune system..