3. Chemical Mediators of Inflammation.

Question 1

What are the 2 groups that chemical mediators are divided into?

Answer 1

Those that are derived from cells and those that are derived from plasma.

Question 2

What are cellular chemical mediators?

Answer 2

Pre-made substances that are located in the cytoplasm of a cell.

Question 3

When are cellular chemical mediators released?

Answer 3

Following the stimulation or lysis of that cell.

Question 4

What are 4 examples of cellular chemical mediators?

Answer 4

Lipid Mediators.

Vasoactive amines.

Cytokines and chemokines.

Lysosomal contents from phagocytic cells.

Question 5

What are plasma chemcial mediators?

Answer 5

Soluble factors that are found in the blood stream.

Question 6

How are plasma chemcial mediators interconnected?

Answer 6

Via a cascade system, this means that when one subunit gets activated it then activates another and so on.

Question 7

Lipid mediators are involved in what pathway?

Answer 7

The arachidonic acid pathway.

Question 8

What enzyme is upregulated when there is damage to the PPL bilayer on cell membranes?

Answer 8

Phospholipase A2.

Question 9

What is the function of phospholipase A2?

Answer 9

It breaks down the phospholipid bilayer and this forms arachidonic acid.

Question 10

What happens to the arachidonic acid that is formed by the destruction of the cell membrane by phospholipase A2?

Answer 10

It is broken down by the cyclooxegenase pathway or the lipooxegenase pathway.

Question 11

What enzymes break down arachidonic acid in the cyclooxegenase pathway ?

Answer 11

Cyclooxegenase-1 (COX-1).

Cyclooxegenase-2 (COX-2).

Question 12

What is made by COX-1?

Answer 12

Thromboxanes and prostaglandins

Question 13

What is made by COX-2?

Answer 13

Prostaglandins.

Question 14

What is made by the lipooxegenase pathway?

Answer 14

Leukotrienes.

Question 15

What is the role of COX-1 in healthy animals?

Answer 15

It helps with the protection of mucosal cells and renal function.

Question 16

When are levels of COX-1 increased?

Answer 16

During inflammation.

Question 17

When is COX-2 expressed?

Answer 17

During inflammation.

Question 18

What is the role of the thrombaxanes that are upregulated during inflammation?

Answer 18

They produce vasoconstriction and platelet aggregation.

Question 19

What are the 5 things produced by prostaglandins during inflammation?

Answer 19

Fever.

Pain.

Vasodilation.

Increased vascular permeability.

Leukocyte adhesion and chemotaxis.

Question 20

How do NSAIDs affect inflammation?

Answer 20

They reduce the up regulation of COX-1 and COX-2.

This reduces the amount of thromboxane and prostaglandins.

This results in less redness, swelling, heat and pain.

Question 21

What changes do we often see if we put an animal of NSAIDs for a long time and why do these changes occur?

Answer 21

Reduced renal function and reduced protection in mucosal areas.

As COX-1 enzymes are active in healthy animals and they are suppressed by NSAIDs.

Question 22

Leukotrienes are involved in what kind of reactions?

Answer 22

Hypersensitivity and allergic reactions.

Question 23

What are the 4 things that leukotrienes can cause in the body?

Answer 23

Smooth muscle contraction.

Vasodilation.

Leukocyte adhesion and chemotaxis.

Mucous secretion.

Question 24

Do leukotrienes or histamine have a more potent response?

Answer 24

Leukotrienes are more potent but have a less rapid response.

Question 25

What produces platelet activating factor following damage to the cell membrane?

Answer 25

Phospholipase A2. Platelet activating factor is a lipid mediator.

Question 26

What is the most potent activator of vascular permeability?

Answer 26

Platelet activating factor. This means it increases the size of gap junctions in the vascular endothelium.

Question 27

What are the 2 things that occur once platelet activating factor has been activated?

Answer 27

WBC chemotaxis and activation. Platelet activation.

Question 28

What are leukocytes?

Answer 28

White blood cells.

Question 29

What is suppressed when an animal is given corticosteroids?

Answer 29

Phospholipase A2. This causes widespread reduction of inflammation.

Question 30

Do NSAIDs or corticosteroids have a better reduction of inflammation?

Answer 30

Corticosteroids, but they have more side effects.

Question 31

What are 5 side effects of glucocorticoids?

Answer 31

Decreased mucosal protection. Increased thirst and urination. Increased blood sugar. Panting and restlessness Immunosuppression.

Question 32

What are 3 examples of vasoactive amines?

Answer 32

Histamine. Serotonin. Nitric Oxide.

Question 33

What are the 3 main cells that produce histamine?

Answer 33

Mast cells. Basophils. Platelets.

Question 34

What cells produce serotonin?

Answer 34

Platelets.

Question 35

What 2 cell types produce nitric oxide?

Answer 35

Macrophages. Endothelial cells.

Question 36

Do vasoactive amines act locally or systemically?

Answer 36

Both.

Question 37

What is the result of the release of vasoactive amines?

Answer 37

Immediate vasodilation that lasts for a short time.

Question 38

Interleukins are a class of what?

Answer 38

Cytokine.

Question 39

What 4 things will interleukins and interferons respond to?

Answer 39

Infection. Hypersensitivities. Inflammation. Cancer.

Question 40

What cells produce interleukins and interferons?

Answer 40

Many different cells.

Question 41

What is influenced by interleukins and interferons?

Answer 41

The innate and adaptive immune systems.

Question 42

What 4 things can activate IL-1?

Answer 42

Fever. Neutrophilia. Activation of endothelial cells. Activation of phospholipase A2.

Question 43

What is stimulated by IL-1?

Answer 43

Acute phase proteins.

Question 44

What 3 things activate TNF-alpha?

Answer 44

Shock. Activation of neutrophils. Activation of endothelial cells.

Question 45

What is stimulated by the activation of TNF-alpha?

Answer 45

The production of other cytokines.

Question 46

What interferon causes a shift from acute to chronic inflammation?

Answer 46

Interferon gamma.

Question 47

What 2 things are activated by interferon gamma?

Answer 47

Macrophages. Lymphocytes.

Question 48

What is the role of IL-10?

Answer 48

Immune system suppression.

Question 49

What are chemokines?

Answer 49

A subclass of cytokines that are involved in the activation of cells and in chemotaxis.

Question 50

What chemokine activates neutrophils?

Answer 50

IL-8.

Question 51

What chemokine activates eosinophils?

Answer 51

Eotaxin (CCL11).

Question 52

What 4 chemokines activate lymphocytes?

Answer 52

CCL1. CCL2. CCL17. CCL20.

Question 53

What chemokine activates monocytes?

Answer 53

Monocyte chemoattractant protein 1 (MCP -1, CCL2).

Question 54

Lysosomal components are found in what 2 immune cells?

Answer 54

Neutrophils. Macrophages.

Question 55

What are 3 examples of lysosomal components found in immune cells?

Answer 55

Reactive oxygen metabolites (free radicals). Antimicrobial peptides Enzymes.

Question 56

The reactive oxygen metabolites found in lysosomal components of immune cells are reactive to what inflammatory mediators?

Answer 56

Pathogens. Host cells.

Question 57

Does thrombaoxane result in vasocontriction or vasodialtion?

Answer 57

Vasoconstriction.

Question 58

What is the complement system comprised of?

Answer 58

Activated proteins that attack pathogens and enhance inflammatory responses.

Question 59

What is the difference between binding in the classical pathway, the mannan-binding lectin pathway and the alternative pathway?

Answer 59

In the classical pathway antibodies bind to antigens. In the mannan-binding lectin pathway lectins bind to mannose. In the alternative pathway there is non-specific binding to the pathogen surface.

Question 60

What is mannose?

Answer 60

A common sugar found on the surfaces of pathogens

Question 61

What is activated when any one of the classical pathway, the mannan-binding lectin pathway or the alternative pathway are activated?

Answer 61

All the pathways end up forming C3-convertase which then forms the membrane attack complex.

Question 62

What is the function of the MAC?

Answer 62

It bores holes in pathogens causing fluids to leak out.

Question 63

What are the 2 anaphylatoxins on the MAC?

Answer 63

C3a. C5a.

Question 64

What is the role of the anaphylatoxins C3a and C5a?

Answer 64

Mast cell degranulation. Vascular dilation, increased permeability. Leukocyte adhesion and chemotaxis.

Question 65

What is the opsonin on the MAC?

Answer 65

C3-B.

Question 66

What occurs when C3-B is activated?

Answer 66

Enhanced phagocytosis by neutrophils and macrophages.

Question 67

Why would an animal with a C3 deficiency be more at risk of developing bacterial meningitis?

Answer 67

As there is a much lower production of the subunits that form the MAC. This means the immune response is not as effective.

Question 68

What would happen if an animals had a defect in C1?

Answer 68

The classical pathway would not work and antibodies would not bind to antigens.

Question 69

How will a C3 deficiency affect the immune response?

Answer 69

Decreased vascular response. Reduced cellular response. Reduced MAC response.

Question 70

How will a C3 deficiency affect the immune response?

Answer 70

The classical pathway will not work.

Question 71

When does the intrinsic pathway for clotting occur?

Answer 71

When there is a platelet plug in the subendothelium. It always occurs when there is damaged tissue.

Question 72

How does a platelet plug activate the the intrinsic pathway for clotting?

Answer 72

It activates factor 12 which starts the cascade.

Question 73

What factor leads to the activation of the intrinsic clotting pathway?

Answer 73

Factor 7.

Question 74

What factor is activated by both the intrinsic and extrinsic pathways?

Answer 74

Factor 10 which leads to the formation of fibrin.

Question 75

What 2 things activate the enzyme kalliekrin?

Answer 75

Microbes. Factor 12.

Question 76

What happens once kalliekrin is activated?

Answer 76

It activates kininogens which then form various kinins.

Question 77

When is the fibrinolytic system activated?

Answer 77

At the same time as the clotting cascade.

Question 78

Why is the fibrinolytic system activated at the same time as the clotting cascade?

Answer 78

To prevent thrombosis from occurring.

Question 79

Plasmin can activate what part of the clotting system?

Answer 79

C3.

Question 80

A massive intravascular immune response promotes what 2 things?

Answer 80

Coagulation. Fibrinolysis.