1. Immune Deficiencies and Lung Infection
1.1. IgG2- capsulated bacteria
1.2. IgG1/3, complement- Gram -ve bacteria
1.3. Lymphocyte- viral infection
1.4. HIV- pneumocystis
1.5. Defensins- cystic fibrosis
1.6. Chemotherapy, surgery and polar age- broad infection
2. Alveolar Epithelial Cells
2.1. Type I Pneumocyte
2.1.1. Extremely thin- 0.2 microns
2.1.2. Squamous, often below limit of detection
2.1.3. Minimal covering for capillaries
2.1.4. Supported by reticular connective tissue and a vasal layer
2.2. Type II Pneumocyte
2.2.1. Cuboidal cells, interspersed amongst Type I cells
2.2.2. Located at angular junction of alveolar walls
2.2.3. Characterised by redish, foamy or vacuolated cytoplasm
2.2.4. Secretory in nature- make surfacant and new type I and II cells
3. B-defensins and Surfactant protein
3.1. Defensins- small cationic detergent peptides
3.1.1. Highly conserved
3.1.2. Active against bacteria, fungi and viruses
3.1.3. Bind to membrane to form pores
3.1.4. Disrupt viral glycoproteins and envelope
3.1.5. High defensin levels associated with infection resistance in CF patiens
3.2. Surfactant proteins- SP A, SP D, C1q, Mannan binding lectin
3.2.1. Ca2+ dependent, collagenous, carbohydrate binding proteins
3.2.2. Bind and agglutinate pathogens
3.2.3. Promote phagocytosis
3.2.4. Fix complement
4. Inflammation during infection
4.1. Epithelial turnover and tight junctions
4.2. Cilial clearance
4.3. Mucus
4.4. Airway shape and longitudinal air flow
4.5. Coughs and sneezes clear diseases
4.6. Humoral branch includes lysozyme, lactoferrin, complement and defensins
4.7. Alveolar macrophages, mast cells
5. Lung Adaptive Immune Mechanisms
5.1. Lung is an immunoresponsive organ
5.1.1. Local IgA/E production in upper airways
5.1.2. Transuded serum IgG in lower airways
5.2. Local autonomous cell mediated immunity
5.2.1. Hylar lymph nodes at main bronchi
5.2.2. Inducible BALT
5.2.3. Parabronchial and parattracheal nodes
6. Effect of smoking
6.1. Weaker response to vaccination
6.2. Lower antibody titre
6.3. Adverse effect of smoking on Hep B vaccine
6.4. More risk of infection, lung tumours, and asthma
6.5. 4 fold increase in macrophage number but poor activation response
6.5.1. Poor APC function
6.5.2. Reduced phagocytic activity
6.5.3. Suppressed cytokine production
6.6. In lymphocytes
6.6.1. Decreased IgG, M, A and sA production but increased IgE production
6.6.2. Decreased functional antibody
6.6.3. Reduced NK function, decreased antigen and mitogen stimulation
6.7. In neutrophils
6.7.1. Increased neutrophil numbers
6.7.2. Reduced chemotaxis, phagocytosis and respiratory burst
6.7.3. Increased peroxidase and elastase activity
7. COPD
7.1. Chronic lung Injury
7.2. Marked by repeated episodes of inflammation
7.3. Continues tissue repair
7.3.1. Distorted matrix deposition
7.3.2. Mesenchymal cells proliferate
7.3.3. Lung architecture is altered
8. COPD Spectrum
8.1. Inhaled agents can cause alveolitis/ pneumonitis
8.2. Circulating agents can cause endothelial injury
9. COPD and fibrosis
9.1. In most cases no known initiating event is recognised, fibrosis is diagnosed
9.2. Th17 cells are activated and lead to
9.2.1. Defensin production by epithelial cells
9.2.2. Inflammatory cytokine production- IL-1 , IL-6, TNF
9.3. This leads to:
9.3.1. Neutropil and macrophage recruitment
9.3.2. Altered mucous production
9.3.3. Epithelial desquamation
9.3.4. Fibroblast proliferation
9.3.5. Collagen deposition
10. Features of Lung Immunity
10.1. Structure and function
10.2. Innate defence mechanisms
10.3. Macrophages
10.4. Adaptive Responses
11. Lung disease
11.1. Infection
11.2. Allergy
11.3. COPD
11.4. Cancer
12. Lung Structure and Function
12.1. Evolved as gas exchange apparatus
12.2. Upper airways conduct- 2 cm^2 cross section
12.2.1. Up to 23 bifurications- trachea to bronchi to bronchioles
12.3. Lower airways facilitate gas exchange- 75m^2 cross section
12.3.1. Respiratory bronchioles, 300m alveoli
12.4. Large mucosal surface
12.4.1. 9000L of air per 24hr resting
12.4.2. Filtration of entire cardiac output
12.5. Effectively sterile- efficiently protected
13. Respiratory epithelium
13.1. Pseudo-stratified columnar epithelium with goblet cells
13.2. Found in airway down to respiratory bronchioles
13.3. Protective- mucus traps particles and removes them by coordinated cilia action
13.4. Tight junctions (zonula occludens)
13.4.1. Variable impermeable barrier to fluid formed by claudin and occludin proteins joining cytoskeleton of adjacent cells
13.4.2. Prevents water loss and entry of infectious/allergenic agents
13.4.3. Increased permeability in asthmatic epithelial cells
14. Asthma
14.1. Allergic Th2 mediated response
14.1.1. Can be induced by exercise, cold air, air pollution, infection, aspirin and obesity
14.2. Common alergens include dander, pollen and dust mites
14.3. Effector cells are IgE prime mast cells, eosinopils and basophils
14.4. Lower chance of Th1 cell mediated autoimmunity like diabetes or MS
14.5. Inflammatory disease of airway wall mediated by TH2 cytokines
14.5.1. IL-5 induces eosinophilia
14.5.2. IL-4 and IL-13 induce goblet cell metaplasia and bronchial hyperreactivity
15. APC in Asthma
15.1. DC
15.1.1. CD11c DC required for IL-3 production by Th2 cells
15.1.2. Plasmacytoid DC required for respiratory tolerance
15.2. Alveolar macrophages
15.2.1. Clear inhaled particles and pathogens
15.2.2. Prime Th1 response
15.2.3. Activated macrophages may be induced by respiratory synctitial virus or sendai virus and prime
15.2.4. Don't migrate to lymph nodes