Stages of Inflammation

Question 1

What first happens when damage to cells occurs?

Answer 1

Cells release inflammatory signals, a result of non-apoptotic cell death and/or detection of foreign material.

Question 2

What do inflammatory signals cause?

Answer 2

Vasodilators to be released such as histamine and nitric oxide.

Question 3

What happens to the blood vessels surrounding the injury?

Answer 3

They become more permeable, more dilated, leak plasma, and have a reduced flow.

Question 4

What does increased permeability and leakage allow?

Answer 4

Increased vascular permeability and leakage allows for more antibodies, proteins and leukocyte to enter the damaged area.

Question 5

What is histamine released by?

Answer 5

Mast cells, basophils and paltelets.

Question 6

What does histamine do?

Answer 6

Vasodilates, increases vascular permeability and activates endothelia.

Question 7

What are prostaglandins released by?

Answer 7

Mast cells and leukocytes.

Question 8

What do prostaglandins do?

Answer 8

Cause vasodilation, pain and fever.

Question 9

What releases TNF and IL-1?

Answer 9

Macrophages, endothelial cells and mast cells.

Question 10

What do TNF and IL-1 do?

Answer 10

Endothelial activation, fever, malaise, pain, anorexia, shock.

Question 11

What produces chemokines?

Answer 11

Leukocytes and activated macrophages.

Question 12

What do chemokines do?

Answer 12

Increased chemotaxis and leukocyte activation.

Question 13

What releases complement proteins?

Answer 13

Plasma (they are produced in the liver).

Question 14

What do complement proteins do?

Answer 14

Leukocyte chemotaxis and activation, vasodilation (through stimulating mast cells) and opsonization.

Question 15

What do we call the fluid that seeps out of blood vessels and into tissues?

Answer 15

Exudate.

Question 16

How are immune cells recruited to the site of infection?

Answer 16

Chemokines are produced and diffuse out to form a gradient. Leukocytes with complementary chemokine receptors migrate towards the chemokine source.

Question 17

What is neutrophil extravasation?

Answer 17

The process of neutrophils leaving the bloodstream and entering the area of damage.

Question 18

What are the four main steps of neutrophil extravasation?

Answer 18

1. Chemo-attraction
2. Rolling Adhesion
3. Tight Adhesion
4. Transmigration

Question 19

How are neutrophils chemo-attracted?

Answer 19

Cytokines cause endothelial upregulation of adhesion molecules known as selectins.

Question 20

What types of selectins bind to neutrophils?

Answer 20

P and E selectins.

Question 21

What is rolling adhesion?

Answer 21

Where carbohydrate ligands in a low affinity state on neutrophils bind to selectins on the endothelia while flowing across the blood stream.

Question 22

What is tight adhesion?

Answer 22

Where chemokines promote low to high affinity switch in integrins such as LFA-1 and MAC-1. This enhances binding to ligands such as ICAM-1/2.

Question 23

What happens in transmigration?

Answer 23

Cytoskeletal rearrangement and extension of pseudopodia (protrusion of part of a cell).

Question 24

What mediates transmigration?

Answer 24

PECAM interactions on both cells.

Question 25

What do neutrophils do at the site of inflammation?

Answer 25

1. Pathogen recognition.
2. Pathogen clearance.
3. Cytokine secretion.

Question 26

How do neutrophils recognise gram-negative bacteria?

Answer 26

Use of TLR4 and CD14 to identify LPS present in GN bacteria.

Question 27

How do neutrophils clear pathogens?

Answer 27

Phagocytosis.

NETosis

Question 28

What is phagocytosis?

Answer 28

Where neutrophils engulf large particles into membrane bound vesicles known as phagosomes.
Phagosomes fuse with lysosomes to produce a phagolysosome and release Reactive Oxygen Species ROS and antimicrobial peptides such as defensins.

Question 29

What is NETosis?

Answer 29

Where neutrophils create Neutrophil extracellular traps which lead to the death of the neutrophil but also any trapped contents.

Question 30

How is inflammation resolved?

Answer 30

1. Pathogens are cleared.
2. The short half life of neutrophils and the rapid turn over of inflammatory mediators prevents prolonged inflammation.
3. Macrophages clear apoptotic cells as well as produce inflammatory mediators.