Pathology 8: Chemical Mediators of Inflammation

Question 1

What are the types of cell derived mediators?

Answer 1

• Vasoactive amines: histamine and serotonin
• Arachondonic acid metabolites
• Nitric oxide (NO)
• Cytokines

Question 2

What are the types of plasma derived mediators?

Answer 2

Complement system

Question 3

Where is histamine stores?

Answer 3

In a performed state in
- mast cells
- basophils
- Platelets

Question 4

How quickly can histamine be released if needed?

Answer 4

Instantly

Question 5

Where are mast cells normally located?

Answer 5

In connective tissues near BV
- may release histamine

Question 6

What is histamine released in response to?

Answer 6

• Physical injury (heat, cold, trauma)
• Immune rxn (IgE binding)
• Presence of complement fragments C3a and C5a (anaphylatoxins)

Question 7

What are the actions of histamine?

Answer 7

• Dilation of arterioles
• Increased vascular permeability of venules

Question 8

what does Increased vascular permeability of venules lead to?

Answer 8

endothelial contraction in venules

Question 9

What is 5-hydrooxytryptamine?

Answer 9

Serotonin

Question 10

Where is serotonin stored preformed? and what is it released in response to?

Answer 10

• Platelets
• Platelet aggregation

Question 11

What is the action of serotonin?

Answer 11

• Dilation of arterioles
• Increased vascular permeability of venules

** Same as histamine

Question 12

Where does arachidonic acid come from?

Answer 12

The degradation of phospholipids by phospholipase

Question 13

What is eicosanoids?

Answer 13

Products of arachidonic acid metabolism

Question 14

What is special about eicosanoids?

Answer 14

it regulates inflammation and homeostasis

Question 15

What are the two primary classes of inflammatory metabolites?

Answer 15

• Prostaglandins and leukotrienes

Question 16

What do corticosteroids inhibit?

Answer 16

The action of phospholipases and therefore any production at all of arachidonic acid

Question 17

What are prostaglandins produced by?

Answer 17

Cyclooxygenases
- COX-1: always expressed
- COX-2: inducible

Question 18

What are the prostaglandins?

Answer 18

Prostacyclins:
- PGE2
- PGI2
- PGF2
- PGD2
Thromboxane:
- TXA2

Question 19

What do asprin and NSAIDS inhibit?

Answer 19

COX-1 and COX-2 therefore inhibiting of prostaglandins

Question 20

What is unaffected by NSAIDS?

Answer 20

lipoxygenase

Question 21

What is lipoxygenase?

Answer 21

An enzyme that produces leukotrienes and lipoxins from arachidonic acid

Question 22

What is leukotrienes actions?

Answer 22

• Chemotaxis for leukocytes
• Vascular effects: vasoconstriction and increased vascular permeability

Question 23

What do lipoxins inhibit?

Answer 23

• Inflammation
• Inhibit leukocyte recruitment and cellular components of inflammation

Question 24

What produces Nitric Oxide?

Answer 24

-Endothelial cells
-Macrophages
- Neurons

Question 25

What is nitric oxide synthesized by?

Answer 25

Nitric oxide synthase

Question 26

What is nitric oxide function in inflammation?

Answer 26

- Vasodilation - Inhibits cellular inflammatory response

Question 27

How does nitric oxide inhibits cellular inflammatory response?

Answer 27

- Reduces platelet aggregation and adhesion (anti-inflammatory) - Inhibits leukocyte recruitment

Question 28

In what form does Nitric oxide kill microbes?

Answer 28

As free radicals

Question 29

What are cytokines?

Answer 29

polypeptides produced primarly by macrophages and lymphocytes

Question 30

What is the action of cytokines?

Answer 30

Modulation of activities of other cells

Question 31

What are the main cytokines involved in acute inflammation?

Answer 31

- IL-1 - TNF (tumor necrosis factor)

Question 32

What are the actions of IL-1 and TNF on vascular endothelium?

Answer 32

- Inc expression of leukocytes adhesion molecules - Production of IL-1 and chemokines - Increase in pro-coagulation and decrease in anticoagulation activity

Question 33

What are the actions of IL-1 and TNF on leukocytes?

Answer 33

- activation - production of cytokines

Question 34

What are the actions of IL-1 and TNF on fibroblasts?

Answer 34

- Proliferation - Increase in collagen synthesis

Question 35

What are the systemic affects of IL-1 and TNF?

Answer 35

- Fever - Leukocytosis - Increased acute-phase proteins - Decreased appetite - Increase sleep

Question 36

What is a complement plasma protein mediator?

Answer 36

- Defense system against microbes - Formation of MAC- membrane attack complex

Question 37

What does compliment activation cause?

Answer 37

- increased vascular permeability - Chemotaxis - Opsonization

Question 38

What are complement proteins stored as?

Answer 38

Inactive plasma precursors: C1-9

Question 39

What are the three pathways of complement activation?

Answer 39

- Classical - Alternative - Lectin

Question 40

What is the classical pathway of complement activation?

Answer 40

- Reaction with IgG and IgM containing antigen-antibody complex

Question 41

What is the alternative pathway of complement activation?

Answer 41

- Contact with microbial surfaces and polysaccharides - Ex: cobra venom and endotoxins

Question 42

What is the lectin pathway of complement activation?

Answer 42

Plasma mannose-binding lectin binds to microbes

Question 43

What does complement activation lead to?

Answer 43

Formation of enzyme C3 convertase

Question 44

What does C3 convertase do?

Answer 44

Cleaves C3

Question 45

what does C3 cleavage lead to?

Answer 45

- Release of C3a (anaphylatoxin) - Covalent attachment of C3b (initiates formation of C5 convertase)

Question 46

What does C5 convertase lead to?

Answer 46

Formation of C5-9 (MAC)

Question 47

What are the complement derived mediators?

Answer 47

- C3a - C5a - C3b

Question 48

What are the anaphylatoxins?

Answer 48

- C3a and C5a

Question 49

What does C3a and C5a do?

Answer 49

Facilitate histamine release from mast cell - Vasodilate - Increase permeability

Question 50

What does just C5a do?

Answer 50

- Activates lipoxygenase pathway of arachidonic acid metabolism in neutrophils and monocytes - Chemotactic for neutrophils, monocytes, eosinophils, and basophils

Question 51

What does c3b do?

Answer 51

Acts as opsonins when fixed to bacteria; facilitating phagocytosis by neutrophils and macrophages (receptor)