Pulmonary Defence Mechanisms Flashcards
What potentially harmful organisms and particles can air contain?
Microorganisms- bacteria, viruses, fungi, helminths
Allergens- dust, pollen
Organic particles- occupational exposures, pollution
Toxic gases- carbon monoxide, sulphur dioxide, nitrogen dioxide
What size/type are the particles in air?
Large particles: Foreign body aspiration (e.g. food, liquid, choke hazards) Fine particulate material: Pollution (<2.5-1000um) Pollen (10-100um) Microscopic pathogens: Fungal spores (2-10um) Bacteria (0.5-5um) Viruses (<1um)
How is the respiratory system vulnerable to damage from inhaled particles?
Allergens trigger an inappropriate and exaggerated immune system response that results in local inflammation and tissue pathology/dysfunction
Inhalation exposure to particular organic particles over the long term can result in chronic restrictive lung disease (e.g. fibrosis, coalminer’s pneumoconiosis) 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)
What mechanisms has the respiratory got to improve immunological defence?
Physical obstructions:
Macro- nasal hairs, turbinates, branching airways
Micro- cilia, mucous
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)
How do nasal hair and turbinates help filter air and prevent particles from reaching the airways?
Nasal hairs within the first 1cm of the nasal passage filter out larger particles present in the air
The nasal turbinates/conchae are mucous membrane-lined, ridged structures within the nasal cavity that help to warm and humidify the air before it reaches the airway/lungs, as well as help to filter out particles larger than around 2um
Impairment through decreased nasal hair density and excessive mouth breathing have both been linked to increased asthma risk/morbidity
How do cilia and mucus function to trap and remove microorganisms and particles/
The upper respiratory system are lined by a layer of mucus produced by submucosal glands (90%) and goblet cells (10%) which traps inhaled particles
Mucus consists of a gel with elastic and viscous properties, which consists of 97% water and 3% solids and also contains lysozyme and various antimicrobial proteins to destroy trapped microorganisms
The mucus gel layer lies on top of a periciliary layer which provides a media of low viscosity in which cilia can beat
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 towards the pharynx, where it is then swallowed or expelled
Cilia beating and mucociliary clearance is produced by rhythmic movement of individual cilia- whilst 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.
Impairment is shown in cystic fibrosis and chronic bronchitis
What are the effects of loss/impairment of mucociliary function?
CFTR mutation ↓ Mucus dehydration + ↓ airway surface fluid ↓ Cilia dysfunction ↓ ↓Mucus clearance
What can happen to someone exposed to tobacco smoke (regularly)?
Tobacco smoke exposure ↓ Airway inflammation ↓ Goblet cell hyperplasia + cilia damage ↓ Mucus hypersecretion + ↓mucus clearance
↑ Respiratory infections
Productive cough
Airway dysfunction & obstruction
What are the protective reflexes that remove irritant or harmful particles from the airways?
The three most identifiable being; coughing, sneezing and the laryngeal expiratory reflex, which result from activation of nociceptors within different parts of the upper respiratory tract
How do protective reflexes happen?
The basic mechanism common to each reflex involves activation of afferent sensory neurons, which transit the impulse to breathing centres within the brain (the medulla)
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
How is each protective reflex initiated?
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 a pressure build-up, and a final expiration phase in which air is expelled (…choo!)
Coughing has the same phases as sneezing but is triggered by stimulation of receptors within the larynx and large airways.
In contrast to sneezing, coughing can be initiated voluntarily, and involves bronchoconstriction to further increase expulsion pressure
The laryngeal reflex is a short, forcible expiratory effort without a preceding inspiration, 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
How does the branching structure if the airways help to filter particles?
The overall structural pattern of the airways to increase filtering of air and prevent particles from reaching lower respiratory structures
When inhaled air reaches an airway branching site, airflow changes from laminar to semi-turbulent flow patter, increasing particle deposition as more particles come into contact with the mucus-lined airway wall
Which resident immune cells provide the last line of defence?
Resident immune cells such as 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
What are alveolar macrophages?
Alveolar macrophages (AM) are the resident phagocytes within the lung and develop form progenitors produced in the bone marrow that migrate to the lung AM are found within the airspace and phagocytose pathogens, foreign material and cell debris, digesting it into residual material that is subsequently removed by the lymphatic system
How do alveolar macrophages contribute to the immunological defence of the pulmonary system?
Certain particles (such as asbestos fibres, silica dust) cannot be digested and cleared by macrophages, triggering inflammation and tissue damage/fibrosis
Macrophages secrete cytokines and ither inflammatory mediators and some macrophage populations can also act as antigen-presenting cells, however alveolar macrophages display very little capacity for this
How do alveolar macrophages relate to pathology?
Transgenic mice deficient in alveolar macrophages, show increased biomarkers of infection and reduced survival following infection with various pathogens, including influenza A virus (see Schneider et al. 2014). Similarly immunocompromised human patients (e.g. AIDS) are at great risk of developing opportunistic respiratory infections such as tuberculosis and bacterial pneumonia.
However whilst the immune system plays a critical role in protecting against pathogens, its activity needs to be balanced against the potential damage caused by excessive/recurrent inflammation (for example in asthma, anaphylaxis, COPD and fibrosis
