Defense Mechanisms of Respiratory Tract

What are sources of injury to respiratory system?

1) Air (Inhaled) 2) Hematogenous 3) Direct Extension (Penetrating injury)

Where do particles 1-2 microns settle?

Bronchiolar/alveolar junction (gravity)

Where do particles 2-10 microns settle?

Bronchus (inertial impaction)

What are the defenses of the air exchange system?

1) Alveoli lack cilia and mucus produce cells 2) No mucociliary clearance 3) MACROPHAGES = primary defense - Exception: Mycobacterium, Listeria, Brucella, Salmonella, Rhodococcus (resistant to degradation w/i macrophages) 4) Local alveolar secretory products - Surfactant -> phagocytosis - Lactoferrin/transferrin (epithelial and inflmmx cells) - Leukocytes produce Lysozyme 5) Alveolar defense against oxidants - Oxidative stress can damage lung - Inhaled oxidant gasses, local toxic metabolites or free radical production by lung macrophages - Epithelial cells of alveoli and bronchi (catalase, superoxide dismutase, vitamin E (natural antioxidants))

What is the mucocilliary clearance/apparatus?

1) Complex of water, glycoproteins, lipid and antibody - Rhythmic movement to remove particulates 2) Mucus covers epithelium and collects particulates and absorbs soluble gases 3) Mucus is coughed up 4) Aerosolized ammonia levels can paralyze cilia (>20ppm)

What is the cost of lung inflammation?

1) Decreased gas exchange (inflammatory exudates) 2) Leukocyte-derived enzymes and oxygen radicals injure/destroy lung tissue 3) Repair processes can permanently decrease lung compliance and thicken the blood-gas barrier -Scarification, fibrosis, collagen

What is deposition and clearance of the conducting system defense?

1) Deposition (particles trapped) -Can overwhelm clearance ability 2) Clearance (Deposited particles are destroed, neutralized or removed from mucosal surfaces) *Must remain in steady state balance

How is the lung protected from blood pathogens?

1) Endothelium diffusion barrier 2) Intravascular macrophages in lung capillaries - Trap and phagocytize stuff, can be overwhelmed 3) Lung primary site of microbial removal in ruminants, cats, pigs, horses (other structure is the liver)

What are the components of mucus found in the mucociliary apparatus?

1) Lactoferrin 2) Lysozyme 3) Beta-defensins - directly toxic 4) IgA, some IgG 5) Collectins - agglutinate/opsonize *Clearance occurs within 2-6 hours

What are M cells?

1) Modified non-ciliated epithelium (microfold cells) 2) Overlies BALT/NALT and phagocytize particulates and antigens 3) Present antigen to macrophages 4) Both cell mediated and humoral immunity 5) Secretory IgA > IgG or IgM 6) Chronic Dz -> BALT/NALT hyperplasia - Hyperplastic tissue can narrow lumen; can impair air movement

What is the first line of defense of the respiratory tract?

1) Mucus 2) Reflexes (Sneezing, coughing) 3) Antibodies and innate defense proteins (kill or opsonize microbes) 4) Alveolar macrophages *Multilayered defence - Goal is to maintain sterile lung WITHOUT inducing inflammation

What causes dysfunction in the respiratory system?

1) Viral infection - Impairs phagocytic function, immunosuppression, direct necrosis of respiratory epithelium 2) Bacterial infection - Bordetella, Mycoplasma ->disrupts cilia 3) Toxins (ammonia, H2S) 4) Immunodeficiency (SCID, steroids, stress) 5) Others (dehydration, anesthesia, etc)

Where do particles <0.3 microns settle?

Alveolus (Diffusion)

What is physical clearance of conducting system defense?

Coughing, sneezing, mucociliary clearance, and phagocytosis

What is the second line of defense of the respiratory tract?

Cytokines produces by macrophages and airway epithelium -> recruit neutrophils and more macrophages -> INFLAMMATION ***If infection can not be contained by first lines of defense.

Where do particles >10 microns settle?

Larynx (inertial impaction)