Pulmonary defence mechanisms

Question 1

How much oxygen do we consume per day?

How much air do we breathe in from the atmosphere?

Answer 1

1. Humans consume ≈ 500L of oxygen/day

2. Inhalation of 8000 L of air/day.

Question 2

What are the two requirements for this huge volume of air to be moved to respiratory surfaces?

Answer 2

• Fast movement of air from atmosphere to respiratory surfaces - places limits on filtering/barrier structures possible.
• Efficient gas exchange - requires a thin membrane innervation by blood vessels, and a warm, moist environment (in which microorganisms also thrive).

Question 3

The air is not sterile, it, therefore, can contain harmful substances, gives some examples

Answer 3

• 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 4

What size and type of particles can air contain?

Answer 4

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

Fine particulate material
• 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)
• 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 5

What do allergens trigger?

Answer 5

Allergens trigger an inappropriate and exaggerated immune system response that results in local inflammation and tissue pathology/dysfunction.

Question 6

What can inhalation of particles over a long period of time cause?

Answer 6

Inhalation of particles over a long period can result in chronic restrictive lung disease due to the damaging effect of particle deposition within respiratory structures and the subsequent immune response triggered. Exposure to certain particles also increases the risk of lung carcinoma (cancer).

Question 7

What mechanisms and features does the respiratory system have to improve immunological function?

Answer 7

Physical obstructions:
• Large scale = nasal hairs, nasal turbinates, branching airway structure.
• Micro scale = cilia, mucus
• Protective reflexes: coughing, sneezing, expiratory reflex

Immunological defence system:
• Lung resident immune cells (e.g. alveolar macrophages)
• Structural cells (epithelial cells)/innate immunity
• Antimicrobial proteins
Biological symbiosis? (commensals/microbiota)

Question 8

What is the function of nasal hairs with the nose?

Answer 8

Nasal hairs within the first 1cm of the nasal passage filter out larger particles (>10μm) present in the air.

Question 9

What is the purpose of nasal turbinates/ conchae

Answer 9

The nasal turbinates/conchae 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 10

Where is mucas produced, what cells produce mucas and what is the purpose of it?

Answer 10

The upper respiratory system (airways and nasal cavity) are lined by a layer of mucus produced by submucosal glands (90%) and goblet cells (10%), which traps inhaled particles

Question 11

Describe the composition of mucus?

Answer 11

Mucus 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 12

How does mucas move?

Answer 12

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 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 13

When does the cilia touch the mucus layer?

Answer 13

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 14

What are the effects of loss/impairment of mucociliary function?

Answer 14

On image

Question 15

Describe the common pathway of neural reflexes to protect the airway from particle exposure

Answer 15

The basic mechanism common to each reflex involves 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 16

Describe how sneezing is initiated?

What stimulates it?

What is the mechanism?

Answer 16

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

Question 17

Describe how coughing is initiated

What stimulates it?

How is it different to sneezing?

Answer 17

Coughing similarly involves these three phases, but is 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 18

Describe the laryngeal reflex

What is it triggered by?

What does it prevent?

What is the mechanism?

Answer 18

(differentiating it from coughing), triggered by stimulation of sensory receptors within the vocal folds. The role of this reflex is to prevent foreign bodies entering the airways, and to expel phlegm and the upper respiratory tract. An initial inspiration before expiration (such as with coughing) is undesired in some circumstances as it could potentially lead to inspiration pneumonia.

Question 19

How does the branching structure of the airway help to filter particles?

How many times does it branch?

How does it work?

Answer 19

Human airways branch approximately 23 times between the trachea and alveoli. 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 20

How do resident immune cells provide the last line of defence?

Answer 20

Resident immune cells (macrophages, and structural cells (e.g. epithelial cells) are present within the tissue structure to provide further defence, coordinate immune responses, and remove deposited particles.

Question 21

What are alveolar macrophages?

Answer 21

Alveolar macrophages (AM) are the resident phagocytes within the lung and develop from progenitors produced in the bone marrow that migrate to the lung.

Question 22

Where are alveolar macrophages found?

Answer 22

AM are found within the airspace (and can travel between alveoli)

Question 23

What do alveolar macrophages do?

Answer 23

Phagocytose pathogens, foreign material and cell debris, digesting it into residual material that is subsequently removed by the lymphatic system.

Question 24

What particles cannot be digested and how are they dealt with?

Answer 24

However certain particles (e.g. asbestos fibers, coal/silica dust) cannot be digested and cleared by macrophages, triggering inflammation and tissue damage/fibrosis. Macrophages constitute part of the innate immune system, and help to trigger further inflammation and an adaptive immune response by secreting cytokines and other inflammatory mediators in response to Toll-like receptor stimulation. Some macrophage populations can also act as antigen presenting cells (presenting antigens to T cells to stimulate cell-mediated immunity, B cell antibody production, etc.), however alveolar macrophages display very little capacity for this.

Question 25

What do leukocytes, structural cells such as epithelial cells and fibroblasts also do?

Answer 25

In addition to leukocytes, structural cells such as epithelial cells and fibroblasts also express pattern recognition receptors, secrete antimicrobial peptides and signal (via cytokine release) to initiate/coordinate immune responses

Question 26

How does the airway and lung microbiota play a role in immunological balance

Answer 26

These organisms play important roles in resisting infection by other pathogens and the development/modulation of a healthy immune system.