7.3 Mechanisms of Lung Inflammation

Question 1

What are the four broad classes of substances/factors that can damage the lungs

Answer 1

• Microbes
• Foreign bodies
• Cell stress
• Allergens

Question 2

Give some examples of types of extracellular microbes that can damage the lungs

Answer 2

• Bacteria
• Fungi
• Parasites

Question 3

Give some examples of types of intracellular microbes that can damage the lungs

Answer 3

• Viruses
• Tuberculosis

Question 4

A pathogen has breached the epithelial lining of the lungs. What are the types of cells that will try and defend the body, and are they adaptive or innate?

Answer 4

Cells such as
- Dendritic cells
- Phagocytes
- NK cells

Will come into action. They are innate.

Question 5

What are defensins? Where in the barrier of the respiratory system are they located?

Answer 5

They are proteins located in the mucous layer of the respiratory tract. Their role is to attack and neutralise pathogens within the mucus layer

Question 6

Which histological layer of the respiratory tissue do innate immune cells reside in?

Answer 6

Lamina propria

Question 7

How do phagocytes call for backup from the adaptive immune system?

Answer 7

By secreting cytokines

Question 8

What type(s) of innate lymphoid cells are involved in infective inflammation?

Answer 8

Type 1 and 3

Question 9

What type(s) of innate lymphoid cells are involved in allergy?

Answer 9

Type 2

Question 10

What are the four main pillars of innate immunity of the lungs?

Answer 10

• Phagocytes
• Dendritic cells
• Innate lymphoid cells
• Cytokines

Question 11

How can pathogens evade the immune system of the lungs in individuals with intact immunity?

Answer 11

• Adherence to epithelial cells (in the case of viruses: adhering and replicating)
• Toxin release (impairs cilia function)

Question 12

Describe three mechanisms by which respiratory immune defenses can be compromised

Answer 12

• Defective mucus (such as in CF)
• Damaged cilia (such as in smokers)
• Defects in immune cells (such as in HIV)

Question 13

Outline the defences of the respiratory systyem against infection (total overview)

Answer 13

• Barrier: epithelial cells, with mucus and defensins in the mucus. Cilia escalate trapped pathogens up to be coughed out or swallowed
• Innate: in lamina propria, we have dendritic cells, phagocytes, innate lymphoid cells and cytokines
• Adaptive: B and T cells as usual

Question 14

Broadly, what type of receptor to innate immune cells rely on to detect extracellular and intracellular pathogens?

Answer 14

Pattern recognition receptors

Question 15

What pro-inflammatory cytokines do innate immune cells release upon recognition of a threat

Answer 15

• IL-6
• TNF alpha

Question 16

How can acute lung inflammation lead to oedema

Answer 16

• Release of inflammatory mediators
• Vasodilation and increased vascular permeability of nearby capillaries
• Fluid leaks into capillaries

Question 17

What is it called when fluid acutely leaks into the alveoli?

Answer 17

Acute respiratory distress syndrome

Question 18

How is acute lung inflammation resolved after it has served its purpose?

Answer 18

• Cells have short half lives, and most naturally die
• Some macrophages stick around and remove alveolar debris
• Lymphatics reabsorb fluid
• Macrophages also release TNF beta to stimulate fibroblast activity (in severe cases)
• Type 2 pneumocytes proliferate to restore alveolar lining

Question 19

Describe the cellular response to intracellular pathogens such as tuberculosis. How does this lead to granuloma formation?

Answer 19

• Pathogen is within phagocytes such as macrophages
• CD4+ T cells secrete inflammatory mediators that cause macrophages to releases reactive nitrogen intermediates and kill the pathogen
• CD8+ T cells then kill the macrophages
• Granuloma forms around necrotic cell; innermost layer is epithelial cells, surrounded by B and T cells

Question 20

How can tuberculosis lead to type 4 hypersensitibity?

Answer 20

• After granuloma formation, T cell activity remains elevated
• Over time, this leads to a type 4 hypersensitivity reaction as a consequence of primary infection

Question 21

In healthy respiratory surfaces, what is the pH range of mucus? Why?

Answer 21

• 5.5-6.7 (somewhat acidic)
• This creates an environment that is not conducive to bacterial growth

Question 22

What are pattern recognition receptors, what is the name of the substances they detect, and what are these substances?

Answer 22

• Pattern recognition receptors detect Pathogen-Associated Molecular Patterns (PAMPs)
• PAMPs are nucleic acids that signal some form of infection (non-specific)

Question 23

What are the two kinds of pattern recognition receptors?

Answer 23

• Toll Like Receptors (TLR)
• Cytosolic receptors

Question 24

How can PRRs differentiate native mRNA from pathogen mRNA?

Answer 24

Our mRNA: methyl group at 5’ end
Foreign: no methyl cap

Question 25

In what instances would cytosolic receptors interpret cytoplasmic dsRNA as a PAMP?

Answer 25

- All of them - That doesn't usually happen

Question 26

Under what instances would cytosolic receptors interpret dsDNA in the cytoplasm as a PAMP

Answer 26

- Every instance - This does not usually occur

Question 27

Are extracellular TLRs often used to detect viral infections?

Answer 27

- no - Viruses are intracellular pathogens; thus, we usually rely on endosomal TLRs to detect viral infection

Question 28

At which point in DNA is it usually methylated?

Answer 28

CpG (Cytosine phosphate Guanine)

Question 29

Name a condition which can be result in inherited mechanical compromise of the immune system

Answer 29

Cystic fibrosis

Question 30

List some acquired conditions/substances that can lead to mechanical compromise of the respiratory immune system

Answer 30

- COPD - Ethanol - Tobacco smoke

Question 31

What is the main cause of disorders of phagocytosis?

Answer 31

Neutropaenia (death of neutrophils)

Question 32

What characterises disorders of humoral immunity?

Answer 32

- Decreased antibody levels - Inability to form new antibodies

Question 33

What two types of drugs can cause disorders of humoral immunity?

Answer 33

- Corticosteroid therapy - Antimetabolite use

Question 34

What diseases can cause disorders of cellular immunity?

Answer 34

- Hodgkin's disease - HIV/AIDS

Question 35

Which age group is most susceptible to pneumonia?

Answer 35

Children under the age of 5