Pulmonary Defence Mechanisms Flashcards
What are the non-specific protective mechanisms in the airways?
- Cough reflex
- Antimicrobials e.g lysozyme
Outline the role of pulmonary macrophages in the immune system.
- Pathogen and dead cell clearance
- Mediate inflammation and tissue repair in response to infection
- Antigen presentation
- Immune surveillance
Describe alveolar macrophages.
- Found in lumen of alveoli
- Prevents alveolar collapse through catabolism of surfactant
- Phagocytosis of exogenous substrates
Describe interstitial macrophages.
- In lung interstitium
- Antigen presentation, tissue remodeling and aids dendritic cell function (prevents airway allergy)
Describe the macrophage response to pulmonary disease.
SEE SLIDES
What type of cells are the pneumocytes?
EPITHELIAL
What are the functions of alveolar type I and II pneumocytes?
- TYPE I - gas exchange between alveoli and blood in capillaries
- TYPE II - surfactant and complement protein secretion
Describe type I pneumocytes
- Flattened and thin in shape - minimised diffusion distance for gas exchange
- Connected by occluding junctions - prevent tissue fluid leakage into alveolar air spaces
- Amitotic - unable to replicate
- Type II cells differentiate to Type I when required
Describe type II pneumocytes.
- Cuboidal and possess granules - store surfactant components
Describe complement activation in the lung.
- Type II pneumocytes synthesise and secrete complement proteins C2-C5 and Factor B
- Cause tissue damage which can result in ARDS, asthma, pneumonia and COPD when overly activated
Describe immune complex-mediated lung injury. PART 1
- Antigen inhaled in lung bound by its antibody. C1q binds to antibody and activates complement cascade
Describe immune complex-mediated lung injury. PART 2
- Lung injury initiates inflammation by complement activation through synthesis of complement proteins from type II pneumocytes
Describe immune complex-mediated lung injury. PART 3
- Complement proteins exacerbate lung inflammation - proteins act as chemoattractants for neutrophils
Describe pulmonary surfactant. PART 1
- Lipid-protein film lines respiratory surface of lungs in mammals
- Reduces surface tension at air-liquid interface in alveoli
- Maintains fluid balance in lung - e.g across alveolar-capillary membrane
Describe pulmonary surfactant. PART 2
- Transports mucus and inhaled particles - prevents adhesion in upper airways
- Aids pulmonary innate immune response - establish barrier against infection
Describe the two hydrophilic proteins found in surfactant
- SP-A and SP-D
- Synthesised and secreted by type II epithelial cells
- Act as collectins
- Recognise, bind and clear pathogens - enhanced phagocytosis by innate immune cells e.g neutrophils, alveolar macrophages
Describe the hydrophobic proteins found in the surfactant.
- SP-B and SP-C
- Contribute to stability of interfacial films
- Involved in interfacial adsorption of surface-active molecules in air-liquid interface
- Deficiencies in protein cause respiratory dysfunction
Describe AMP (antimicrobial peptide)
- Expressed at airway mucosal surfaces
- Antibacterial and antiviral properties
- Inhibits biofilm formation, viral replication
- Involved in opsonisation and facilitates phagocytosis
- Modulates inflammation and toxin neutralisation
Give examples of AMP
- Lactoferrin - bactericidal, antiviral and bacteriostatic glycoprotein. Limits iron for microbe growth - destabilises outer membrane for Gram-negative bacteria
- SLPI - similar to lactoferrin. Inhibits viral DNA synthesis - defense against elastases
- Lyzosyme - bactericidal and bacteriostatic. Targets peptidoglycan cell wall
Describe alpha-1 antitrypsin
- Protease inhibitor - protects lung tissue from enzymes of inflammatory cells
- Produced in liver and bone marrow by lymphocytic and monocytic cells in lymphoid tissue
- Dampens effects of elastase - which can damage elastin in lungs
Give two conditions in which alpha-1 antitrypsin deficiency is implicated.
- COPD
- Emphysema
Describe changes in alpha-1 antitrypsin function.
- Mutation of glutamic acid to lysine causing abnormal folding
- 10-15% develop liver fibrosis/cirrhosis - antitrypsin not secreted properly - accumulates in liver
- Cigarette smoke can also cause inactivation
Describe IgA
- Most common Ig in secretions
- Found in either monomeric/dimeric forms
- Forms antibody-antigen complexes
- Involved in opsonisation
- Neutralise pathogens - bind to viral surface proteins that allow viral entry into host cells
Compare and contrast IgA1 and IgA2.
- Half -life of IgA1 is 5-7 days and IgA2 is 4-6 days
- 11-14% of IgA1 in serum, IgA2 1-4% in serum
- IgA1 activated by alternative and lectin pathways. No activation for IgA2
- Both interact with epithelial cells, phagocytes
Describe antiviral B cell immunity in the lungs. PART 1
- T helper cells activate B cells - antibody-secreting cells/memory cells produced
- Dendritic cells carrying viral antigens, migrate to secondary and tertiary lymphoids. Present antigens to B cells
Describe antiviral B cell immunity in the lungs. PART 2
- Antigen recognition initiates differentiation - B cells migrate to lymphoids and proliferate
- Contact with CD+ T helper cells recognise antigen presented by B cell via MHC Class II
- Ig isotype class switching from IgM to IgG or IgA and proliferation
Describe T helper cells and cytotoxic cells. PART 1
- CD4+ T helper cells help B cells mount antibody response
- Provide feedback to dendritic cells via co-stimulatory molecules
- CD4+ T cells perform cytotoxic functions, mediate macrophage activation and induce genes in mucosal tissues - contribute to host defense
Describe T helper cells and cytotoxic cells. PART 2
- Enhance and maintain responses of CD8+ cytotoxic T cells
- CD8+ T cells contribute to cytokine production and kill viral-infected cells
Describe T cells in lung diseases
- In COPD and CF, reduced anion transported in lung epithelial cells
- Reduced airway surface liquid and reduced antimicrobial activity
- Persistent inflammation and chronic T cell activation/proliferation
- Parenchymal lung damage
