MCBoM- Chemical mediators of Inflammation

Question 1

Vasoactive amines

Answer 1

HISTAMINE
Widely distributed, from mast cells, basophils and platelets
Released by these cells in response to physical injury or immune reaction
Causes dilation of arterioles and increased vascular permeability of venules
SEROTONIN
In platelets and enterochromaffin cells
Similar action to histamine

Question 2

Plasma proteases- Complement system

Answer 2

Found in plasma
Requires activation: C1 by classical or lectin pathways, C3 by alternative pathways
Causes lysis of microbes by MAC (membrane attack complex) C5-9
C3b -opsonin
C5a -chemotactic agent
C3a and C5a -anaphylotoxins

Question 3

Plasma proteases- Coagulation system

Answer 3

Found in plasma
Requires activation
Converts soluble fibrinogen to fibrin
Some play a role in inflammation:
thrombin-> increased leukocyte adhesion, fibroblast proliferation
fibrinopeptide-> increased vascular permeability, chemotaxis
factor Xa-> increased vascular permeability, leukocyte exudation

Question 4

Plasma proteases- Kinin system

Answer 4

Found in plasma
Requires activation
Activation causes release of bradykinin, leading to increased vascular permeability, contraction of smooth muscle, vasodilation, pain

Question 5

Arachidonic acid metabolites

Answer 5

AA is 20 carbon polyunsaturated fatty acid
Derived from diet or by conversion from lenoleic acid (essential FA)
Esterified in membrane phospholipids
Metabolites are eicosanoids, synthesised by cyclooxygenase and lipooxygenase

Question 6

Cytokines

Answer 6

Proteins mainly produced by lymphocytes and macrophages, modulates function of other cell types
Monokines- produced by monocytes
Lymphokines- produced by lymphocytes
Chemokines- cytokines that have the ability to stimulate leukocyte movement (chemokinesis) and directed movement (chemotaxis)
IL1 and TNF are major mediators of inflammation
-> more sleep, decreased appetite, more acute phase proteins

Question 7

Nitric Oxide

Answer 7

Soluble gas produced by endothelial cells, macrophages and specific neurones in brain
Short half life, so paracrine effect (local)
Functions:
-vasodilator
-antimicrobial activity
-pathogenesis of shock
-decreased leukocyte adhesion and migration
-decreased platelet aggregation and adhesion

Question 8

Platelet Activating Factor (PAF)

Answer 8

From platelets, basophils/mast cells, neutrophils, monocytes/macrophages, endothelium
Functions:
-activation of platelets
-chemotaxis
-bronchoconstriction
Low concs-> vasodilation, increased vascular permeability
High concs-> vasoconstriction

Question 9

Lysosomal constituents of leukocytes

Answer 9

Neutrophils and monocytes contain lysosomal granules

• Larger azurophilic/primary granules
• Smaller specific/secondary granules

Question 10

Vasodilation

Answer 10

-Prostaglandins
-Nitric Oxide
So more blood to site of injury, provides WBCs and antibodies

Question 11

Increased vascular permeability

Answer 11

-Vasoactive amines
-C3a and C5a
-Bradykinin
-Leukotrines
-PAF
So chemicals can leave the blood to get to the tissue, site of injury

Question 12

Chemotaxis and leukocyte activation

Answer 12

-C5a and leukotrines
-Chemokines
-Bacterial products
To guide WBCs to site of injury so can activate and destroy injurious agent

Question 13

Fever

Answer 13

• IL1, IL6, TNF

- Prostaglandins

Question 14

Pain

Answer 14

• Prostaglandins

- Bradykinin

Question 15

Tissue damage

Answer 15

-Neutrophil and macrophage lysosomal enzymes
-Oxygen metabolites (free radicals produced by cell)
-Nitric Oxide
To protect the body, just some collateral damage