Lecture 3: Inflammation and the Innate Immune Response

Question 1

What are the 3 lines of defense/phases of the immune response?

Answer 1

Barriers
Innate
Adaptive

Question 2

Describe barriers:

Answer 2

➢ First line of defense
➢ Block or destroy pathogens when they enter the body
➢ i.e. skin, mucosal membranes

Question 3

Describe the innate immune response:

Answer 3

➢ Non-specific attack by molecules, cells, and mechanisms
➢ Triggered by cell or tissue damage
➢ i.e. Inflammation

Question 4

Describe the adaptive immune response:

Answer 4

➢ APC activate T and B cells

➢ Specific antibody production and coordinated cell attack

Question 5

Explain what Rubor is and its cause:

Answer 5

Redness

Cause:
➢ Increased blood flow accounts for the redness
➢ Vasodilation occurs soon after the injury = accelerated blood flow
➢ Histamine causes vasodilation

Question 6

Explain what Calor is and its cause:

Answer 6

Heat

Cause:
➢ Increase in blood flow also causes an increase in heat

Question 7

Explain what Dolor is and its cause:

Answer 7

Pain

Cause:
➢ Swelling puts pressure on local pain receptors = pain and loss of function

Question 8

Explain what Tubor is and its cause:

Answer 8

Swelling

Cause:
➢ Following the increase in blood flow, the microcirculation becomes more permeable
➢ Allows the leakage of protein-rich fluid into the interstitial space
➢ Leukotrienes produced by the mast cells increase vascular permeability

Question 9

What does Histamine do?

Answer 9

Found in many cell types, causes vasodilation

Question 10

What do Kinins do?

Answer 10

Released from damaged tissues, recruits more phagocytes

Question 11

What do Prostaglandins do?

Answer 11

Intensify the effects of Histamine and Kinins, help phagocytes out of the blood and into the tissues

Question 12

What do Leukotrienes do?

Answer 12

Promote adherence of phagocytes and increase vascular permeability

Question 13

Which cytokines secreted by macrophages cause inflammation?

Answer 13

IL-1β
TNF-α
IL-6
CXC18
IL-12

Question 14

How do tissue resident macrophages cause inflammation?

Answer 14

They release cytokines that increase the permeability of blood vessels and chemokines that attract other phagocytes

Question 15

________ differentiate into macrophages and move towards the site of damage

Answer 15

Monocytes

Question 16

__________ released due to inflammation cause the __________ cells in the blood vessels to express _________.

Answer 16

Chemokines
Endothelial
Selectins

Question 17

Explain leukocyte rolling:

Answer 17

Leukocytes roll along the endothelial walls due to weak interaction with selectins and their ligands and integrins (on the cell), eventually, they bind stably (stable adhesion due to chemokine signalling) and squeeze between the cells to exit the vessel

Question 18

WBC can only exit through the _______

Answer 18

veins

Question 19

What are the 5 stages of phagocytosis?

Answer 19

• Chemotaxis
• Adherance
• Ingestion
• Digestion
• Excretion

Question 20

What happens during the chemotaxis stage?

Answer 20

• Phagocytes move up the chemokine concentration gradient to reach the site of inflammation

Question 21

What happens during the adherence stage?

Answer 21

• Membrane of the phagocyte makes contact with the pathogen

Question 22

What happens during the ingestion stage?

Answer 22

• Pseudopods envelop the pathogen

- A vesicle forms around the pathogen = phagosome

Question 23

What happens during the digestion stage?

Answer 23

• Phagosome fuses with a lysosome =pagolysosome

- Enzymes from the lysosome digest the pathogen

Question 24

What happens during the excretion stage?

Answer 24

• After digestion, the phagolysosome is filled with fragments and is called a residual body
• Residual bodies migrate to the cell surface and are exocytosed

Question 25

What is the acute phase response?

Answer 25

A response to pathogen invasion and is related to inflammation, trauma and infection

Question 26

What are acute phase proteins?

Answer 26

proteins that enhance (+’ve acute phase proteins) or inhibit (-‘ve acute phase proteins) inflammation

Question 27

What are some acute phase proteins and their functions?

Answer 27

• Cytokines: IL-6 causes the production of more acute phase proteins
• Fibrinogen: Used for clotting
• Kinins: Increase vasodilation
• C-reactive protein: binds phospholipid
• Mannose-Binding Protein: binds to mannose on microbe surface and activates the C’ pathway

Question 28

Both C-reactive protein and Mannose-Binding Protein attract _________.

Answer 28

Phagocytes

Question 29

What is a fever?

Answer 29

A systemic rise in body temperature

Question 30

What is an antipyretic?

Answer 30

A substance used to control fever

Question 31

What are the benefits of a fever?

Answer 31

• Speeds up the host’s defenses

- Lowers plasma Fe and inhibits microbial growth

Question 32

What are the disadvantages of a fever?

Answer 32

• Denatures proteins
• Inhibits CNS function
• Causes dehydration and electrolyte imbalance
• In extreme cases can lead to coma

Question 33

What is resolution?

Answer 33

• Wounds heal back to original state
• Governed by key lipid, proteins, peptides and gaseous mediators
• Requires orchestrated processes by innate immune cells
• Spent neutrophils undergo apoptosis and are removed by macrophages which kick-starts resolution

Question 34

What is chronic inflammation?

Answer 34

• If the injurious agent is not removed then it progresses to chronic inflammation
• Granuloma can be formed, chronic activation of Macrophages by Th1 cells mediates the formation
• Granulomas contain the pathogen, macrophages circle around a pathogen that can’t be removed

Question 35

What is fibrosis?

Answer 35

• Too much damage to be repaired normally

- Fibroblasts lay day collagen and other proteins to fill in where tissue has died