THE IMMUNE SYSTEM OF THE RESPIRATORY TRACT

Location Host Defense Mechanism*

Upper Airways (trap particles > 10 um)

Nasopharynx Nasal hair

Turbinates

Waldeyer’s Ring: pharyngeal and tubal tonsils (pathologies: acquired or congenital immundeficiency disorders, lymphomas, CLL, myeloma)Mucociliary apparatus (pathologies: increased mucosal viscosity & thickness: CF, asthma, chronic bronchitis ORMucocilliary dyskinesia due to smoking, anaesthetics, bronchiectasis, immotile cilia syndrome)IgA secretion (selective IgA deficiency: common 1:400)

Location Host Defense Mechanism*

Upper Airways (trap particles > 10 um)

Oropharynx

Saliva (contains fibronectin, IGA, lactoferrin, lysozyme, peroxidase, secretory leukocyte proteinase inhibitor. (Saliva secretion reduces with ageing)Waldeyer’s Ring palatine and lingual tonsils (pathologies: acquired or congenital immundeficiency disorders, lymphomas, CLL, myeloma)

Sloughing of epithelial cells

Cough reflex (pathologies: CVA, ventilator, lung transplant, elderly, neonates, smoking, paralysis, neuromuscular disorders)Complement production (low levels C3 & C4 with SLE)

Waldeyer’s Ring

MALT Tissue

The MALT tissues relevant to the respiratory system are:

NALT (Waldeyer’s ring of tonsilar tissue from the upper nasopharynx (adenoids) to the posterior tongue – inducer and effector

LALT laryngeal lymphoid tissue BALT (bronchus associated lymphoid

tissue: found in peribronchial, perivascular and interstitial areas of the lung

Conducting Airways (trap 2-10 um particles)

Trachea & BronchiSharp-angled branching of airways (particle forward momentum causes lodgement in airway surface liquid)Mucociliary apparatus

Airway surface liquid (lysozyme, lactoferrin, secretory leukocyte proteinase inhibitor)

Dendritic cells Antigen processing and presentation to Th lymphocyte →stimulation of memory and effector T cells and B cells

Bronchus-associated lymphoid tissue (BALT)

Immunoglobulin production (IgG, IgM, IgA)

Lower Respiratory Tract (most bacteria are 0.5-2 um and can reach alveoli)

Terminal airways, alveoli

No mucocillary apparatus but alveolar lining fluid contains surfactant, FFAs, fibronectin, IGG, complement, iron-binding proteins)

Alveolar & intravascular macrophages (phagocytosis, cytokines)Neutrophil recruitment(pattern recognition receptors→transcription factor stimulation→proinflammatory and anti-inflammatory cytokine and chemokine production)

Interstitial macrophages (lung connective tissue)Dendritic cells (alveolar septa)Bronchus-associated lymphoid tissue (BALT)

Antigen processing and presentation to CD4+Th & secretion of cytokines→stimulation of effector T cells (by IL2) and B cells (by IL4, IL13 & IFN-γ)

Impairment of Defences

Impaired epiglottic closure: stroke, seizure, drug abuse, normal sleep -> aspiration of oropharyngeal flora

Alcohol Impairs epiglottic and cough reflex Alters colonisation of oropharynx – G+ve to G-ve Decreased neutrophil mobilisation & effectiveness Blocks TNF response to endotoxin Induces macrophage secretion of IL10

(antiinflammatory) Tobacco impairs mucociliary & macrophage

functions

Impairment of Defences Mycoplasma and H.influenza

Impair ciliary function Influenza A

Destroys cilia causing mucus buildup and 2nd infections Extrapulmonary sepsis decreases lung clearance of bacteria Burn inhalation injury with ventilator support (50% incidence of

pneumonia, 37% mortality rate). Drugs: especially cancer chemotherapy, immunosuppressants, proton

pump and H2 inhibitors Other factors that impair pulmonary host defenses include old age,

premature birth, hypoxaemia, acidosis, toxic inhalations, pulmonary oedema, malnutrition

Lymphadenopathy due to compression from sarcoidosis, solid tumours Bronchial obstruction due to adenocarcinoma Systemic disease: diabetes, renal failure, GORD, COAD, CHF, HIV Splenectomy: encapsulated bacteria like S.pneumoniae must be

opsonised then removed by splenic macrophages, or else!