Pulmonary defence mechanisms

Question 1

why are the lungs a site of immunological invulnerability

Answer 1

• Fast movement of air in and out of the lungs- place limits on level of filtering/barrier structures possible
• Efficient gas exchange - large S.A, thin membrane, warm, moist environment at blood gas interface - microbes can thrive

Question 2

Potentially damaging particles/organisms

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

What size/types of particles can air contain

Answer 3

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

Fine particulate material

• Pollution (<2.5 - 1000 μm)
• Dust (0.1-1000 μm)
• Pollen (10 - 100 μm)

Microscopic pathogens

• Fungal spores (2 - 10 μm)
• Bacteria (0.5 - 5 μm)
• Viruses (< 1 μm)

Question 4

Physical features to limit risk of infections

Answer 4

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

Question 5

Protective reflexes to limit risk of infection

Answer 5

Coughing, sneezing, expiratory reflex

Question 6

Immunological defence system to limit risk of infection

Answer 6

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

Question 7

Nasal hairs

Answer 7

Filter out large particles (>10μm) present in the air.

Question 8

Nasal turbinates/conchae

Answer 8

Are 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 9

Make up of mucus

Answer 9

Consists of 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 10

Mucus layer function

Answer 10

The mucus gel layer lies on top of a periciliary layer (≈ 7μm deep) which provides a media of low viscosity in which cilia can beat. Maintaining sufficient periciliary layer depth is critical to effective mucociliary clearance for this reason. As the respiratory tract is lined by ciliated epithelium

Question 11

Cilia

Answer 11

The coordinated beating of cilia produces a wave of movement that propels the mucus gel layer towards the pharynx, where it is then swallowed or expelled.

Question 12

How is cilia beating produced

Answer 12

Cilia beating and mucociliary clearance is produced by rhythmic movement of individual cilia
- 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 13

Cystic fibrosis & chronic bronchitis

Answer 13

mucus clearance is impaired leading to recurrent respiratory infections and resulting inflammation/tissue damage.

Question 14

3 most distinct reflexes to remove harmful particles

Answer 14

sneezing
coughing
laryngeal expiratory reflex

Question 15

What activates the 3 distinct reflexes

Answer 15

Nociceptors within different parts of the upper respiratory tract

Question 16

Afferent sensory neurons

Answer 16

Transmit impulse to breathing centres within the brain

Question 17

Efferent signals

Answer 17

• Then transmitted to specific respiratory muscles, glottis and airways to initiate a coordinated respiratory effort which rapidly expels air from nasal cavity/airways/lungs
• Via parasympathetic & motor nerves

Question 18

How is sneezing initiated

Answer 18

• Stimulation of sensory receptors within nasal cavity
• Deep inspiration phase
• Compression phase (glottis is closed leading to pressure build up)
• Final expiration phase which air is expelled

Question 19

How is coughing initiated

Answer 19

Stimulated by receptors within the larynx and large airways
Can also be voluntary
Involves bronchoconstriction to further increase expulsion pressure

Question 20

Laryngeal reflex

Answer 20

Short, forcible expiratory effort without a preceding inspiration

Question 21

How is a laryngeal reflex stimulated

Answer 21

Stimulation of sensory receptors within the vocal folds

Question 22

Role of laryngeal reflex

Answer 22

Prevent foreign bodies entering airways and to expel phlegm in upper respiratory tract

Question 23

How does the branching structure of airways help to filter particles

Answer 23

• Increase filtering of air and prevent particles form reaching lower respiratory structures
• When inhaled air reaches and airway branching site airflow changes from laminar to semi-turbulent flow pattern, increasing particle deposition - particles come into contact with mucus lined airway wall

Question 24

Alveolar macrophages

Answer 24

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

Question 25

Important role of alveolar macrophages

Answer 25

Prevent respiratory infections

Question 26

How does airway/lung microbiota help to maintain immunological balance

Answer 26

The mucosal surfaces of the respiratory system are not sterile (even in healthy individuals) – they are colonised by huge numbers of commensal bacteria.
These organisms play important roles in resisting infection by other pathogens and the development/modulation of a healthy immune system.