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Disease and Defense: Unit 2 > Chemical Mediators of Inflammation > Flashcards

Chemical Mediators of Inflammation Flashcards

1
Q

Is histamine (H) cellular-derived or plasma protein-derived?

A

It is a cell derived mediator

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2
Q

Name two vasoactive amines.

A
  1. Histamine

2. Serotonin

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3
Q

What are the effects of histamine?

A
  1. Arterial dilation

2. Endothelial contraction

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4
Q

Name three cells that release histamine

A
  1. Mast cells
  2. Basophils
  3. Platelets
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5
Q

What inactivates histaminase?

A

Histaminase

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6
Q

Name 6 things that initiate the release of histamine from mast cells.

A
  1. Physical causes (mechanical or temperature)
  2. Immune- binding of IgE
  3. Compliment (C3a, C5a)
  4. Histamine releasing proteins (from leukocytes)
  5. Neuropeptides
  6. Cytokines (IL-1, IL-8)
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7
Q

What is the effect of serotonin on vessels?

A

Vasoconstriction to aid in clotting

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8
Q

What cells in the blood contain serotonin?

A

Platelets contain serotonin granules

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9
Q

Where is arachidonic acid (AA) derived from?

A

AA is derived from cell membrane phospholipids and is transformed into a number of compounds that mediate inflammation and hemostasis

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10
Q

Name four sources of arachidonic acid (AA).

A
  1. Leukocytes
  2. Mast cells
  3. Endothelium
  4. Platelets
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11
Q

What two things can inactive arachidonic acid (AA)?

A
  1. Spontaneous decay

2. Enzymes

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12
Q

AA metabolites are formed by two main pathways.
1. Cyclooxygenase
2. Lipoxygenase
What does each pathway produce?

A
  1. Cyclooxygenase- prostaglandins and thromoboxanes

2. Lipoxygenase- Leukotrienes and lipoxins

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13
Q

What drugs interact with AA metabolism?

A

NSAIDs block cyclooxygenase

Glucocorticoids block phopholipase A2 (which shuts down the whole AA pathway)

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14
Q

Prostaglandins are produced by what pathway?

A

Cyclooxygenase

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15
Q

What are the effects of prostaglandins?

A

They contribute to symptoms of pain and fever

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16
Q

What two compounds are produced by the lipooxygenase pathway?

A
  1. Leukotrienes

2. Lipoxins

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17
Q

What are the functions of leukotrienes?

A

Mediate specific functions in inflammation. Ex. Chemotactic for neutrophils

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18
Q

What compound is generated by leukocytes as they enter tissue?

A

Lipoxins

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19
Q

What are the functions of lipoxin?

A

They antagonize leukotrienes and are anti-inflammatory. Ex. Inhibit neutrophil chemotaxis

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20
Q

Name three functions of platelet-activating factor.

A
  1. Platelet aggregation
  2. Vasodilation
  3. Vascular permeability
  4. Bronchoconstriction
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21
Q

How are platelet-activating factors produced?

A

Similarly to AA: phospholipase A2 cleaves lipids from cell membranes

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22
Q

Are cytokines part of the innate or adaptive immune system?

A

Both

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23
Q

What are the functions of TNF and IL-1?

A

They cause endothelial activation (leukocyte binding and recruitment)

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24
Q

What are some systemic effects of TNF and IL-1?

A
  1. Fever

2. Acute phase protein synthesis

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25
Q

What produces TNF and IL-1?

A

Macrophages, mast cells, and endothelial cells

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26
Q

What stimulates macrophages, mast cells, and endothelial cells to produce TNF and IL-1?

A

Presence of microbial products, immune complexes and T cell mediators

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27
Q

Chemokines are small proteins separated into two groups based on structure. What are the two groups?

A
  1. CXC

2. CC

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28
Q

What is the primary function of chemokines?

A

Chemotaxis, but also activates leukocytes.

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29
Q

What is the function of CXC?

A

Chemotactic for neutrophils (IL-8)

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30
Q

What is the function of CC?

A

Chemotactic for a variety of cells (e.g. eotaxin for eosinophils)

31
Q

What is the function of IFN-gamma?

A

Stimulates classical macrophage activation

32
Q

What is the function of IL-12?

A

Stimulate the growth and function of T cells

33
Q

What cell(s) release reactive oxygen species (ROS)?

A

Neutrophils and macrophages

34
Q

Name three forms of reactive oxygen species (ROS).

A
  1. *O2- (NADPH oxidase pathway)
  2. *OH
  3. HOCL* (Myeloperoxidase in neutrophils)
35
Q

What enzyme protects host cells from reactive oxygen species?

A

Superoxide dismutase

36
Q

What are four functions of NO?

A
  1. Free radical that kills microbes
  2. Vasodilation
  3. Antagonizes platelet activation
  4. Reduces leukocyte recruitment
37
Q

What is NO produced from?

A

L-arginine

38
Q

What enzyme converts L-arginine to NO?

A

Nitric oxide synthase (NOS)

39
Q

From what cells is type II, inducible NOS produced?

A

Macrophages and endothelial cells.

40
Q

What induces macrophages and endothelial cells to make Type II, inducible NOS?

A

IL-1, TNF, INF-gamma and bacterial endotoxin. This NO is related to inflammation

41
Q

From what cell is type III, endothelial NOS produced?

A

….Endothelial. It is constitutively expressed in endothelial cells

42
Q

What cells produce lysosomal enzymes?

A
  1. Neutrophils- azurophil granules

2. Monocytes- granules

43
Q

What is the function of lysosomal enzymes?

A

To kill microbes and digest ingested materials, but it can also damage host tissue

44
Q

In what environment is acid protease activated?

Neutral protease?

A

Within the phagolysosome (low pH)

Activated outside the cell (neutral pH)

45
Q

What mitigates damage of the host tissue from proteases?

A

Protease inhibitors

46
Q

Name two protease inhibitors and their functions.

A
  1. Alpha-1-antitypsin: neutrophil elastase inhibitor

2. Alpha-2-Macroglobulin: Inhibits a large variety of proteinases

47
Q

Are the granules within the neutrophil all the same??

A

No!! They are different and have different functions

48
Q

What is the function of neuropeptides?

A

They initiate inflammation particularly active in vascular tone and permeability

49
Q

What organs are neuropeptides particularly active?

A

The lung and the GI

50
Q

What is substance P?

A

A neuropeptide that is 11 amino acids long.

  • Secreted by nerves and inflammatory cells
  • binds the neurokinin-1 receptor
  • generates proinflammatory effects in immune and epithelial cells
51
Q

Is complement plasma protein derived or cell derived?

A

Plasma protein-derived mediator

52
Q

Is compliment involved in an inflammatory or immune process?

A

Both

53
Q

What does compliment do to vasculature and leukocytes?

A

Causes increased vascular permeability and leukocyte chemotaxis

54
Q

How is compliment activated?

A

Proteolysis

55
Q

What enzyme converts C3 to C3a and C3b?

A

C3 Convertase

56
Q

What three separate pathways lead to C3 convertase formation?

A
  1. Classical
  2. Alternative
  3. Lectin
57
Q

What is the function of C3a and C5a?

A

They increase vascular permeability and stim mast cells to release histamin

58
Q

What is the function of C5a?

A

Activates the lipogenous pathway for AA metabolism

59
Q

What is the function of C5a, C4a, C3a?

A

Activate leukocytes increasing their endothelial adhesion. Also chemotactic agents for neutophils, eopinophils, basophils, and monocytes

60
Q

What is the function of C3b?

A

Acts as opsonin for enhanced phagocytosis

61
Q

What is the function of MAC?

A

Essentially multiple C9 proteins (formed by 5b-C9). Creates pores that violate the membranes of some bacteria

62
Q

What is the function of C1 inhibitor?

A

Blocks activation of C1

63
Q

What is the function of decay-accelerating factor (DAF) and factor H?

A

Limit C3/C5 convertase formation

64
Q

Where are inhibitors of complement found?

A
  1. Free within the plasma

2. Associated with cells protect host tissue

65
Q

What are three functions of Factor XII (Hageman factor)?

A
  1. Activates the kinin system
  2. Stimulates the clotting cascade, including several other factors that impact inflammation
  3. Whenever clotting system is activated, so the fibrinolytic system
66
Q

What is the function of kenin system?

A
  1. Eventually becomes bradykinin which causes increased vascular permeability, vascular dilation and pain
  2. Intermediate product Kallikrein is chemotactic and activates Factor XII
67
Q

What is a function of Factor Xa?

A

Leads to vascular permeability

68
Q

What are three functions of thrombin in inflammation?

A
  1. Binds to protease activated receptors on endothelial cells, activating them
  2. Cleaves fibrinogen creating fibrinopeptides which increase vascular permeability and are chemotactic
  3. Cleaves compliment factor 5 forming factor 5a
69
Q

What role does the fibrinolytic system play in inflammation?

A

Releases active inflammatory mediators resulting in vascular permeability, dilation and C3a formation

70
Q

What antagonizes leukotrienes?

A

Lipoxins

71
Q

What antagonizes complement?

A

Compliment regulatory proteins (C1 Inhibitor)

72
Q

What antagonizes the activation of macrophages?

A

IL-10

73
Q

What is the function of TGF-beta?

A

Promotes fibrosis and is anti-inflammatory

Disease and Defense: Unit 2 (12 decks)

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