Pulmonary Defence Mechanisms

Question 1

What are the non-specific protective mechanisms in the airways?

Answer 1

• Cough reflex
• Antimicrobials e.g lysozyme

Question 2

Outline the role of pulmonary macrophages in the immune system.

Answer 2

• Pathogen and dead cell clearance
• Mediate inflammation and tissue repair in response to infection
• Antigen presentation
• Immune surveillance

Question 3

Describe alveolar macrophages.

Answer 3

• Found in lumen of alveoli
• Prevents alveolar collapse through catabolism of surfactant
• Phagocytosis of exogenous substrates

Question 4

Describe interstitial macrophages.

Answer 4

• In lung interstitium
• Antigen presentation, tissue remodeling and aids dendritic cell function (prevents airway allergy)

Question 5

Describe the macrophage response to pulmonary disease.

Answer 5

SEE SLIDES

Question 6

What type of cells are the pneumocytes?

Answer 6

EPITHELIAL

Question 7

What are the functions of alveolar type I and II pneumocytes?

Answer 7

• TYPE I - gas exchange between alveoli and blood in capillaries
• TYPE II - surfactant and complement protein secretion

Question 8

Describe type I pneumocytes

Answer 8

• 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

Question 9

Describe type II pneumocytes.

Answer 9

• Cuboidal and possess granules - store surfactant components

Question 10

Describe complement activation in the lung.

Answer 10

• 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

Question 11

Describe immune complex-mediated lung injury. PART 1

Answer 11

• Antigen inhaled in lung bound by its antibody. C1q binds to antibody and activates complement cascade

Question 12

Describe immune complex-mediated lung injury. PART 2

Answer 12

• Lung injury initiates inflammation by complement activation through synthesis of complement proteins from type II pneumocytes

Question 13

Describe immune complex-mediated lung injury. PART 3

Answer 13

• Complement proteins exacerbate lung inflammation - proteins act as chemoattractants for neutrophils

Question 14

Describe pulmonary surfactant. PART 1

Answer 14

• 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

Question 15

Describe pulmonary surfactant. PART 2

Answer 15

• Transports mucus and inhaled particles - prevents adhesion in upper airways
• Aids pulmonary innate immune response - establish barrier against infection

Question 16

Describe the two hydrophilic proteins found in surfactant

Answer 16

• 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

Question 17

Describe the hydrophobic proteins found in the surfactant.

Answer 17

• 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

Question 18

Describe AMP (antimicrobial peptide)

Answer 18

• 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

Question 19

Give examples of AMP

Answer 19

• 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

Question 20

Describe alpha-1 antitrypsin

Answer 20

• 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

Question 21

Give two conditions in which alpha-1 antitrypsin deficiency is implicated.

Answer 21

• COPD
• Emphysema

Question 22

Describe changes in alpha-1 antitrypsin function.

Answer 22

• 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

Question 23

Describe IgA

Answer 23

• 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

Question 24

Compare and contrast IgA1 and IgA2.

Answer 24

• 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

Question 25

Describe antiviral B cell immunity in the lungs. PART 1

Answer 25

- 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

Question 26

Describe antiviral B cell immunity in the lungs. PART 2

Answer 26

- 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

Question 27

Describe T helper cells and cytotoxic cells. PART 1

Answer 27

- 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

Question 28

Describe T helper cells and cytotoxic cells. PART 2

Answer 28

- Enhance and maintain responses of CD8+ cytotoxic T cells - CD8+ T cells contribute to cytokine production and kill viral-infected cells

Question 29

Describe T cells in lung diseases

Answer 29

- 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