BCR 15 - Respiratory Infections

What are the three main categories of host pulmonary defences?

Mechanical defences, local innate defences, and systemic adaptive defences

How do mechanical defences protect the respiratory tract?

They repel, block or eject invading microorganisms before they establish infection

What are local innate defences in the lung?

Immune responses that act at epithelial surfaces using soluble factors and innate immune cells

What are systemic adaptive defences in respiratory infection?

Humoral and cell mediated immune responses that are antigen specific and provide memory

How do pulmonary defences change during infection?

They are upregulated and systemic immune cells migrate into the lungs to act locally

Why is the respiratory tract particularly vulnerable to infection?

It is in continuity with the external environment

What are the key anatomical features of the upper respiratory tract?

Air filled cavities lined with epithelium, covered with mucus, containing saliva and a resident microbiome

Is the upper respiratory tract sterile?

No, it contains a nasal and oropharyngeal microbiome

Why is the upper respiratory tract a common portal of entry for pathogens?

It connects directly to both the respiratory and gastrointestinal tracts

How does air normally travel through the upper respiratory tract?

Through the nose over the turbinates to the posterior pharynx, under the epiglottis and into the trachea

What is the function of the epiglottis during swallowing?

It closes over the trachea to prevent aspiration into the lower airways

How do nasal hairs protect against infection?

They block the entry of large inhaled particles

How do the nasal turbinates contribute to host defence?

They increase surface area and create turbulence to trap particles in mucus

What is the role of mucus in the upper respiratory tract?

It traps inhaled particles and microorganisms

What is the function of the sneeze reflex?

It expels trapped particles, irritants and pathogens from the nasal passages

How do epithelial tight junctions act as a defence mechanism?

They form a physical barrier preventing pathogen entry between cells

How does saliva contribute to mechanical defence?

It washes epithelial surfaces and maintains epithelial integrity

How does mucus contribute to local immune defence?

It traps pathogens and contains antimicrobial substances

What antimicrobial enzyme is found in saliva and mucus?

Lysozyme

How does the microbiome protect against respiratory infection?

It resists colonisation by pathogenic organisms

How can systemic antibiotics increase respiratory infection risk?

They disrupt the normal microbiome, reducing colonisation resistance

What are the main structural features of the lower respiratory tract?

Branching airways lined by ciliated columnar epithelium that end in alveoli

Were the lower airways historically considered sterile?

Yes, but low density microbiota have now been identified

What is the pleural space?

A space outside the lung that is not in continuity with the airways

How can the pleural space become infected?

By spread from lung infection or via the bloodstream

What is meant by a safe swallow?

Coordinated pharyngeal and laryngeal muscle action that prevents aspiration into the lower airways

How does aspiration increase infection risk?

It allows non sterile upper airway contents to enter the lower respiratory tract

What is the function of the cough reflex?

It expels mucus, bacteria and inflammatory cells from the airways

Why is normal ventilation important for preventing infection?

Patent and structurally normal airways allow effective clearance of secretions and pathogens

What is the mucociliary escalator?

A coordinated system of cilia and mucus that moves trapped particles towards the throat for removal

Where is the mucociliary escalator found?

In the nasal passages, trachea and bronchi

How does disruption of the mucociliary escalator affect infection risk?

It increases susceptibility to respiratory infection

What type of epithelium lines the conducting airways?

Ciliated columnar epithelium covered with mucus

What are cilia?

Microscopic hair like projections from epithelial cells that beat rhythmically

How do cilia contribute to host defence?

They propel mucus and trapped particles towards the throat for swallowing or coughing

What is the normal ciliary beat frequency?

Approximately 12 to 15 Hz

What produces airway mucus?

Goblet cells

What are mucins?

Glycoproteins that form the structural basis of mucus

What are the two layers of airway mucus?

An outer gel layer and an inner periciliary layer

What is the function of the gel layer of mucus?

It traps dust, particles and microorganisms

What is the function of the periciliary layer?

It allows cilia to beat freely and effectively

What happens to mucus containing trapped pathogens?

It is swallowed or coughed out

How does lysozyme kill bacteria?

It cleaves the peptidoglycan layer of bacterial cell walls

What are defensins?

Small cationic peptides that disrupt microbial membranes

How does complement contribute to respiratory defence?

It kills bacteria directly and enhances phagocytosis

What is lactoferrin and how does it act?

An iron binding glycoprotein that inhibits bacterial growth and blocks some viral entry

What are type 1 interferons?

Cytokines that inhibit viral replication and protect uninfected cells

What is the role of neutrophils in respiratory infection?

They are recruited during infection to phagocytose and kill pathogens

Are neutrophils normally present in healthy airways?

No, they are recruited during inflammation

What is the role of macrophages in the lung?

They phagocytose pathogens, initiate inflammation and present antigen to lymphocytes

Where are alveolar macrophages located?

They reside in the alveoli of healthy lungs

What is the role of natural killer cells in the lung?

They recognise and kill cells infected with intracellular pathogens

What is the function of eosinophils in pulmonary defence?

They participate in defence against multicellular parasites

What are type 1 pneumocytes?

Alveolar lining cells involved in gas exchange

What are type 2 pneumocytes?

Alveolar cells that produce surfactant and antimicrobial peptides

What is surfactant?

A phospholipid substance that reduces surface tension and supports immune defence

How does surfactant contribute to host defence?

It reduces microbial adherence and enhances phagocytosis

What are pattern recognition receptors?

Receptors on immune and epithelial cells that detect conserved microbial structures

How does antigen presentation initiate adaptive immunity?

Dendritic cells and macrophages present processed antigens to naïve T cells in lymph nodes

How are helper and cytotoxic T cells generated?

Naïve T cells differentiate after antigen presentation in lymph nodes

How are B cells activated in respiratory infection?

Helper T cells release cytokines that stimulate B cells to produce antibodies

What are the main functions of immunoglobulins in the lung?

Neutralisation, complement activation and opsonisation of extracellular pathogens

What is the role of IgM in infection?

It is the earliest antibody produced in acute infection

What is the role of IgG in respiratory infection?

It prevents infection, limits haematogenous spread and reduces disease severity

What is the role of IgA in mucosal immunity?

It is secreted into mucus and prevents pathogens from establishing infection

How can IgA deficiency affect the lungs?

It predisposes to recurrent pulmonary infections

What is the function of CD8 positive cytotoxic T cells?

They kill infected cells and release cytokines

What is the function of CD4 positive helper T cells?

They coordinate immune responses and support cytotoxic T cells and B cells

What is the role of Th1 cells in pulmonary defence?

They secrete interferon gamma to activate macrophages against intracellular pathogens

What is the role of Th2 cells in pulmonary defence?

They promote responses against extracellular pathogens and recruit eosinophils

Why is cell mediated immunity critical in lung infections?

It is essential for controlling intracellular pathogens

What is meant by pathogenesis of respiratory infection?

The processes by which a microorganism establishes infection and causes disease

What must a pathogen achieve to cause lower respiratory tract infection?

Reach the host, access lower airways, adhere, survive, multiply and cause tissue damage

What are the main routes by which pathogens reach the lower airways?

Inhalation, migration from upper airway, aspiration and haematogenous spread

How does aspiration lead to pneumonia?

Failure of airway protection allows upper airway contents to enter the lungs

What is haematogenous spread in respiratory infection?

Dissemination of pathogens via the bloodstream to the lung or pleural space

What are the two main modes of respiratory pathogen transmission?

Direct inhalation and indirect contact transmission

How does particle size affect deposition in the respiratory tract?

Smaller particles penetrate deeper into lower airways and alveoli

What size particles are typically filtered in the nose?

Approximately 10 micrometres

What size particles can reach the alveoli?

Less than 2 micrometres

What is an aerosol?

A particle less than 5 micrometres that can reach lower airways

What is a droplet in respiratory transmission?

A particle larger than 5 to 10 micrometres that usually deposits in upper airways

How is SARS-CoV-2 transmitted?

Through aerosols and droplets, with risk increased by close proximity and poor ventilation

Why does intubation increase transmission risk of SARS-CoV-2?

It generates high levels of infectious aerosols

What are adhesins?

Microbial surface proteins that bind to host epithelial receptors

What are pili and how do they aid infection?

Hair like bacterial structures that enhance adherence to epithelial cells

How does biofilm formation enhance pathogenicity?

It allows strong adherence and protects bacteria from host defences

How can pathogens interfere with the mucociliary escalator?

By secreting toxins that paralyse cilia

What is transcytosis?

Transport of pathogens across epithelial cells from apical to basolateral surfaces

What is receptor mediated endocytosis in infection?

Binding to specific host receptors that triggers internalisation into cells

How can immune cells transport pathogens across epithelium?

By phagocytosing but failing to kill them, allowing intracellular transport

How does epithelial cell death promote infection?

It disrupts barrier integrity allowing deeper invasion

How do bacterial toxins weaken epithelial barriers?

They disrupt tight junctions enabling paracellular migration

How does smoking increase pneumonia risk?

It damages respiratory epithelium and impairs mucociliary clearance

How do bacteria evade phagocytosis?

By killing phagocytes or inhibiting complement mediated opsonisation

What is the function of a bacterial capsule?

It prevents complement binding, phagocytosis and antibody recognition

How do respiratory viruses evade interferon responses?

By producing proteins that suppress interferon signalling

How does intracellular survival help pathogens evade immunity?

It hides them from antibodies and some innate mechanisms

What is antigenic variation?

Mutation of surface antigens allowing escape from adaptive immunity

What are anti immunoglobulin proteases?

Bacterial enzymes that degrade antibodies