Inflammation

Question 1

What are the 4 classical descriptions of inflammation?

Answer 1

Rubor, tumor, calor and dolor (redness, swelling, heat and pain respectively).

Question 2

What is cellulitis?

List 2 common causes.

Answer 2

• Acute skin infection.
• Commonly caused by:

1 - Streptococcus pyogenes.

2 - Staphylococcus aureus.

Question 3

What is the function of inflammation?

Answer 3

To destroy, dilute or wall off an injurious agent and induce repair.

Question 4

List 6 components of barrier immunity.

Answer 4

Physical barriers:

1 - Skin.

2 - Lungs.

3 - Gut.

Active barriers:

4 - Cilia.

5 - Secretions.

6 - Antibacterial peptides.

Question 5

Give an overview of the acute phase response of the innate immune system.

Answer 5

1 - Recognition of the danger signal by innate immune cells.

2 - Response mediated by:

• Cellular activation.
• Cellular recruitment.
• Cytokine activation.
• Complement activation.

3 - Destruction of the pathogen and resolution of inflammation or recruitment of adaptive immune response.

Question 6

How are threats recognised by the innate immune system?

Answer 6

Via pattern recognition receptors (especially on mast cells, however pattern recognition receptors are present on every innate immune cell).

Question 7

List 3 functions of mast cells.

Answer 7

1 - To detect injuries via pattern recognition receptors.

2 - To release histamine and other mediators.

3 - To initiate the inflammatory response.

Question 8

List 3 functions of histamine.

Answer 8

1 - To cause vasodilation.

2 - To widen the endothelial junction, increasing permeability.

3 - To cause irritation of nerve endings, causing itching and pain.

Question 9

List 2 mediators of inflammation.

Answer 9

1 - Histamine.

2 - Arachidonic acid metabolites (eicosanoids).

Question 10

List 3 eicosanoids that mediate inflammation.

Through which pathways are they produced?

Answer 10

Through the COX pathway:

1 - Prostaglandins.

2 - Thromboxane.

Through the lipoxygenase pathway:

3 - Leukotrienes.

Question 11

List 2 effects of COX pathway products.

Answer 11

1 - Vasodilation.

2 - Prolongation of oedema.

Question 12

List 4 effects of leukotrienes.

Answer 12

1 - Vasoconstriction.

2 - Chemotaxis.

3 - Increase vascular permeability.

4 - Bronchospasm.

Question 13

What is montelukast?

Answer 13

A leukotriene receptor antagonist used in asthma.

Question 14

List 2 drugs that block the COX pathway.

Answer 14

1 - Aspirin.

2 - NSAIDs.

Question 15

Give an example of a use of prostaglandins.

Answer 15

Prostaglandins are used to treat pulmonary hypertension.

Question 16

How do nonsteroidal anti-inflammatory drugs (NSAIDs) prevent inflammation?

Answer 16

By blocking the COX pathway.

Question 17

What is the cause of erythema?

Answer 17

Vasodilation.

Question 18

What is the cause of oedema?

Answer 18

Increased vascular permeability.

Question 19

Which type of proteins are the cause of localised heat during inflammation?

Answer 19

Cytokines.

Question 20

List 2 advantages of vasodilation during inflammation.

Answer 20

1 - Increases blood flow and pooling, increasing migration of activated cells to the tissues.

2 - Increases local temperature.

Question 21

What is the advantage of increased endothelial permeability during inflammation?

Answer 21

The fluid loss into tissue leads to concentration and stasis of red blood cells in local vessels.

Question 22

Why is blood stasis advantageous during inflammation?

Answer 22

Because blood stasis contributes towards the migration of immune cells towards the offending agent.

Question 23

List 3 acute phase cytokines.

Answer 23

1 - IL-1.

2 - TNF-alpha.

3 - IL-6.

Question 24

List 6 responses of the body to acute phase cytokines.

Answer 24

1 - The endothelium vasodilates and increases permeability.

2 - The hypothalamus increases the ‘set’ temperature.

3 - Fat and muscle increase mobilisation of energy stores.

4 - The liver increases production of acute phase proteins such as C-reactive protein (CRP).

5 - The bone marrow increases mobilisation of neutrophils.

6 - Dendritic cells release tumour necrosis factor, which stimulates maturation and migration to lymph nodes (initiates the adaptive immune response).

Question 25

List 3 drugs that are blockers of the acute phase response.

Which diseases are these drugs used to treat?

Answer 25

Used to treat inflammatory bowel disease and rheumatoid arthritis:

1 - Anti TNF-alpha.

Used to treat rheumatoid arthritis:

2 - Anti IL-1.

3 - Anti IL-6.

Question 26

What is a risk of overproduction of TNF-alpha and IL-1?

Answer 26

Septic shock.

Question 27

List the stages of development of septic shock.

Answer 27

1 - Endotoxins (lipopolysaccharides) are released from gram-negative bacteria such as E. coli.

2 - The endotoxins enter the circulation and cause massive activation of macrophages in the liver and spleen.

3 - This results in the overproduction of TNF-alpha and IL-1.

4 - This leads to dilation of blood vessels, leakage of fluid into tissues throughout the body and widespread clotting.

5 - These factors collectively cause multiple organ failure.

Question 28

What are granulomas?

What is their function?

Answer 28

• Large organisations of macrophages.

- They function to wall off infections.

Question 29

List 4 outcomes of acute inflammation.

Answer 29

1 - Healing with scar formation.

2 - Abscess formation (encapsulation and pus).

3 - Granuloma formation.

4 - Chronic inflammation (when acute phase can’t be resolved).

Question 30

List 2 factors that might contribute to an unresolved acute phase.

Answer 30

1 - Persistent injury or infection.

2 - Autoimmune disease states such as rheumatoid arthritis and systemic lupus erythematosus.

Question 31

List 3 mechanisms of chronic inflammation.

Answer 31

1 - Cellular infiltration (granuloma formation).

2 - Tissue destruction by inflammatory cells (such as with COPD).

3 - Attempts at repair with fibrosis and angiogenesis.

Question 32

What is the average lifespan of a neutrophil?

Why is this important?

Answer 32

• Between a few hours and a day.

- This is important for terminating acute inflammation when necessary.

Question 33

List 2 anti-inflammatory cytokines.

Answer 33

1 - TGF-beta.

2 - IL-10.

Question 34

How do anti-inflammatory cytokines prevent inflammation?

Answer 34

By inhibiting the production of pro-inflammatory cytokines.

Question 35

List 5 acute phase proteins (APPs).

Answer 35

1 - C-reactive protein (CRP).

2 - C3.

3 - C4.

4 - Fibrinogen.

5 - Ferritin.

Question 36

List 3 negative control proteins for the acute phase response.

Answer 36

1 - Alpha-1 antitrypsin.

2 - Albumin.

3 - Transferrin.

Question 37

List 2 functions of C-reactive protein (CRP).

Answer 37

1 - To opsonise bacteria and fungi.

2 - To activate the classical complement cascade by binding to C1q.

Question 38

What is erythrocyte sedimentation rate (ESR)?

Answer 38

The rate at which erythrocytes settle out of unclotted blood in one hour.

Question 39

Why does erythrocyte sedimentation rate (ESR) change with inflammation?

Answer 39

• Normally, erythrocytes are very buoyant and settle slowly.
• Erythrocytes are negatively charged and repel, preventing aggregation.
• In the presence of acute phase reactants, erythrocytes aggregate due to the loss of their negative charge, resulting in increased sedimentation.

Question 40

What is the effect of IL-1 and IL-6 on bone marrow?

Answer 40

Release of neutrophils from bone marrow neutrophil stores.

Question 41

What is a leukaemoid reaction?

What might cause a leukaemoid reaction?

Answer 41

• Leukocytosis in response to stress or infection.

- Can be caused by exaggeration of leukocyte release in response to IL-1 and IL-6 at the bone marrow.