Lecture 11 - simplified

Question 1

What are the major actions of soluble mediators?

Answer 1

1. Act as switches
2. Messengers-controlling actions of cells
3. Stimulate pain

Question 2

Briefly outline the origins of important soluble mediators:

Answer 2

1. Liver produces the plasma factors these include Factor XII (Hageman factor) and also complement activation
2. Cellular
   - some are preformed (Histamine and Serotonin)
   - others are newly synthesised

Question 3

Briefly describe the plasma protein cascades in order of when they are activated:

Answer 3

1. Hageman Factor (Factor XII) activates coagulation (clotting) cascade and also the kinin cascade
2. Kinin cascade then activates the fibrinolytic cascade via the action of Kalikrein
3. The plasmin then activates the complement cascade

Question 4

What is the main link between the coagulation system and inflammation?

Answer 4

Thrombin is the main link between the system because it activates fibrinogen to fibrin which is a major coagulation protease.

Question 5

Briefly describe the functioning of the kinin system:

Answer 5

1. generates vasoactive peptides (from plasma protein kininogens) from the action of specific proteases (kalikrienens)
2. The activation of the kinin system produces bradykinin. Bradykinin is short lived and quickly deactivated. (causes smooth muscle contraction, increased vascular permeability, dilation of blood vessels)
3. Kinin system is activated by Hageman Factor (XII) and Kalikrien is a potent activator of Factor XII

Question 6

What is the role of fibrin in the clotting cascade?

Answer 6

1. Increases wbc adhesion and provides a scaffold for them
2. Acts as a glue to trap foreign agents
3. Allows for fibroblast proliferation and collagen production

Question 7

What is the role of fibrin degradation products?

Answer 7

1. Increases vascular permeability
2. Increases leukocytes in exudates
3. Increases chemotaxis (esp. neutrophils)

Question 8

Explain the roles of C3b, C3a, C5a and C5b in the complement cascade?

Answer 8

C5a and C3a: cause inflammation
C3b: causes phagocytosis
C5b: MAC- causes lysis of microbe.

Question 9

Where do Histamine and Serotonin come from?

Answer 9

Histamine and Serotonin and performed within secretory granules within the cell.

Question 10

What are the main effects of Histamine an Serotonin on the cell?

Answer 10

• They stimulate arteriolar dilation, extravascular smooth muscle contraction and increase venue permeability
• Pain (serotonin)
• Chemoattractant for eosinophils (Histamine)

Question 11

When will histamine be released by mast cells?

Answer 11

1. In response to physical injury
2. Immune reactions
3. Fragments of complement (anaphylotoxins)
4. Histamine releasing proteins from leukocytes
5. Neuropeptides (substance P)
6. Cytokines

Question 12

What Arachidonic acid metabolite (Eicosanoid) does a steroid inhibit?

Answer 12

Steroids inhibit phospholipase

Question 13

What Arachidonic acid metabolite (Eicosanoid) do NSAID’s inhibit?

Answer 13

Cyclooxyrgenase

Question 14

What are the functions of the Lipoxins

Answer 14

• inhibit leukocyte recruitment
• inhibit neutrophil chemotaxis and adhesion
• negative regulators of leukotrienes

Question 15

What is the basic functions of Resolvins?

Answer 15

• inhibit leukocyte recruitment + activation

Question 16

What is another name for cytokines and what is the function of them?

Answer 16

• Small molecular weight protein messengers that are activated and are produced by leukocytes after activation
• The major actions of them include endothelial activation, leukocyte activation, fibroblast recruitment, priming of neutrophils, differentiation of lymphocyte subsets

Question 17

What are the main interleukins that are involved in acute inflammation?

Answer 17

IL-1, IL-6 and TNF alpha

Question 18

What is the immediate systemic response to the release to cytokine release?

Answer 18

Systemic: Endotoxic shock
Brain: Fever- appetite + sleep
Bone marrow: Neutrophilia - phagocytosis
Liver: Acute phase proteins