Pulmonary Defence Mechanisms Flashcards

1
Q

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

A
  • Cough reflex
  • Antimicrobials e.g lysozyme
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2
Q

Outline the role of pulmonary macrophages in the immune system.

A
  • Pathogen and dead cell clearance
  • Mediate inflammation and tissue repair in response to infection
  • Antigen presentation
  • Immune surveillance
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3
Q

Describe alveolar macrophages.

A
  • Found in lumen of alveoli
  • Prevents alveolar collapse through catabolism of surfactant
  • Phagocytosis of exogenous substrates
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4
Q

Describe interstitial macrophages.

A
  • In lung interstitium
  • Antigen presentation, tissue remodeling and aids dendritic cell function (prevents airway allergy)
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5
Q

Describe the macrophage response to pulmonary disease.

A

SEE SLIDES

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6
Q

What type of cells are the pneumocytes?

A

EPITHELIAL

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7
Q

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

A
  • TYPE I - gas exchange between alveoli and blood in capillaries
  • TYPE II - surfactant and complement protein secretion
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8
Q

Describe type I pneumocytes

A
  • 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
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9
Q

Describe type II pneumocytes.

A
  • Cuboidal and possess granules - store surfactant components
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10
Q

Describe complement activation in the lung.

A
  • 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
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11
Q

Describe immune complex-mediated lung injury. PART 1

A
  • Antigen inhaled in lung bound by its antibody. C1q binds to antibody and activates complement cascade
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12
Q

Describe immune complex-mediated lung injury. PART 2

A
  • Lung injury initiates inflammation by complement activation through synthesis of complement proteins from type II pneumocytes
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13
Q

Describe immune complex-mediated lung injury. PART 3

A
  • Complement proteins exacerbate lung inflammation - proteins act as chemoattractants for neutrophils
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14
Q

Describe pulmonary surfactant. PART 1

A
  • 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
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15
Q

Describe pulmonary surfactant. PART 2

A
  • Transports mucus and inhaled particles - prevents adhesion in upper airways
  • Aids pulmonary innate immune response - establish barrier against infection
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16
Q

Describe the two hydrophilic proteins found in surfactant

A
  • 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
17
Q

Describe the hydrophobic proteins found in the surfactant.

A
  • 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
18
Q

Describe AMP (antimicrobial peptide)

A
  • 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
19
Q

Give examples of AMP

A
  • 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
20
Q

Describe alpha-1 antitrypsin

A
  • 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
21
Q

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

A
  • COPD
  • Emphysema
22
Q

Describe changes in alpha-1 antitrypsin function.

A
  • 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
23
Q

Describe IgA

A
  • 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
24
Q

Compare and contrast IgA1 and IgA2.

A
  • 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
25
Q

Describe antiviral B cell immunity in the lungs. PART 1

A
  • 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
26
Q

Describe antiviral B cell immunity in the lungs. PART 2

A
  • 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
27
Q

Describe T helper cells and cytotoxic cells. PART 1

A
  • 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
28
Q

Describe T helper cells and cytotoxic cells. PART 2

A
  • Enhance and maintain responses of CD8+ cytotoxic T cells
  • CD8+ T cells contribute to cytokine production and kill viral-infected cells
29
Q

Describe T cells in lung diseases

A
  • 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