LocationHost Defense Mechanism** Upper Airways (trap particles > 10 um) NasopharynxNasal 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 OR Mucocilliary dyskinesia due to smoking, anaesthetics, bronchiectasis, immotile cilia syndrome) IgA secretion (selective IgA deficiency: common 1:400)

LocationHost 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)

 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 & Bronchi Sharp-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 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 )

 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

 Mycoplasma and H.influenza  Impair ciliary function  Influenza A  Destroys cilia causing mucus buildup and 2 nd 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!