Mediators of inflammation

Question 1

What are the 5 hallmarks of inflammation?

Answer 1

redness (rubor), swelling (tumour), heat (calor; only applicable to the body’ extremities), pain (dolor) and loss of function (functio laesa).

Question 2

What are the 5 steps of inflammation?

Answer 2

• Recognition
• Recruitment
• Removal
• Regulation
• Repair

Question 3

What are the benefits of inflammation?

Answer 3

• Dilutiion/inactivation of biological and chemical toxins
• Killing/ sequestering/degradation of microbes, foreign material, nectrotic material and neoplastic cells
• Providing wound healing factors
• Restricting movement allowing time for repair
• Increasing temperature to induce vasodilation and inhibit replication of pathogens

Question 4

What are harmful consequences of inflammation?

Answer 4

• Could be misdirected (allergies including asthma)
• Could be excessive, prolonged and difficult to control

Question 5

Give an example of an agent that is difficult to control and can cause excessive collateral damage.

Answer 5

Tuberculosis

Question 6

Give an example of a surface that cannot engulf an agent.

Answer 6

Ag/Ab on immovable flat surface such as the glomerular basement membrane

Question 7

What are the main cells involved in acute inflammation?

Answer 7

Neutrophils

Question 8

What are the vascular effects of acute inflammation?

Answer 8

• Dilation
• Congestion
• Increased permeability (oedema, plasma proteins in tissue, emigration of leukocytes from microcirculation)

Question 9

How long does the onset of acute inflammation take?

Answer 9

Minutes or hours

Question 10

How long does the onset of chronic inflammation take?

Answer 10

Days

Question 11

What are the main cells involved in chronic inflammation?

Answer 11

Lymphocytes, plasma cells, macrophages

Question 12

What causes chronic inflammation?

Answer 12

• Persistant infection
• Hypersensitivity (auto-immune and allergy)
• Prolonged exposure to potential toxic agents

Question 13

What are the most important mediators of acute inflammation?

Answer 13

• Vasoactive amines
• Lipid products
• Cytokines/chemokines
• Complement proteins

Question 14

What are the major producers of mediators of acute inflammation?

Answer 14

Macrophages, mast cells and dendritic cells

Question 15

What are the minor producers of mediators of acute inflammation?

Answer 15

Platelets, neutrophils, endothelial cells, epithelial cells

Question 16

Give 2 examples of vasoactive amines.

Answer 16

Histamine and Serotonine

Question 17

What cells produce Histamine?

Answer 17

Mast cells, Basophils, Platelets

Question 18

What causes histamines to be released?

Answer 18

• Trauma
• Cold
• Heat
• Binding of Abs (IgE)
• Complement fragments C3a and C5a (anaphylatoxins)

Question 19

What cells produce serotonin?

Answer 19

Platelets and neuroendocrine cells

Question 20

What are the effects of serotonin on blood vessels?

Answer 20

Vasoconstriciton

Question 21

Give 3 examples of Arachdonic acid metabolites (eicosanoids).

Answer 21

• Prostoglandins
• Leukotriens
• Lipoxins

Question 22

What Arachdonic acid metabolite has an anti-inflammatory function?

Answer 22

Lipoxins

Question 23

What cells are prostoglandins produced by?

Answer 23

Mast cells, macrophages, endothelial cells and platelets

Question 24

What cells are Leukotreins produced by?

Answer 24

Mast cells and Leukocytes

Question 25

What cells are involved in the first step of Lipoxin synthesis?

Answer 25

Leukocytes (especially neutrophils)

Question 26

What enzymes convert Arachdonic acid to Prostaglandin?

Answer 26

COX1 and COX2

Question 27

What inhibits Prostaglandin synthesis?

Answer 27

Aspirin, NSAIDS, selective COX2-inhibitors

Question 28

What enzymes convert Arachdonic acid to Leukotriens?

Answer 28

Lipoxygenase (3 types)

Question 29

What inhibits Leukotrien synthesis?

Answer 29

5- Lipoxygenase inhibitor, LT-R-antagonist

Question 30

What cells are involved in the second stage of Lipoxin synthesis?

Answer 30

Platelets

Question 31

What enzyme converts Arachdonic acid to Lipoxin?

Answer 31

Lipoxygenase

Question 32

Why does Lipoxin have an anti-inflammatory reaction?

Answer 32

It inhibits the recruitment of Leukocytes

Question 33

What cells produce Cytokines?

Answer 33

Mainly Macrophages but also lymphocytes, dendritic cells, epithelial, endothelial and CT cells

Question 34

What are the roles of Cytokines?

Answer 34

- Endothelial activation (expression of adhesion molecules and mediators) - Leukocyte activation (response to stimuli and microbiocidal action) - Systemic acute phase response including fever, and presence of cachexia

Question 35

Give examples of Cytokines.

Answer 35

TNF, IL-1, IL-6, IL-17

Question 36

What is the function of IL-6?

Answer 36

Local and systemic inflammation

Question 37

What is the function of IL-17?

Answer 37

Neutrophil recruitment

Question 38

What are the 4 major groups of chemokines?

Answer 38

C CC CXC CX3C

Question 39

What group of chemokines are Lymphocytes attracted to?

Answer 39

C and CC

Question 40

What group of chemokines are monocytes, basophils, eosinophils and lymphocytes in?

Answer 40

CC

Question 41

What group of chemokines are neutrophils attracted to?

Answer 41

CXC

Question 42

What are the 3 main functions of chemokines?

Answer 42

- stimulation of leukocyte attachment to endothelium (via integrins) - Maintenance of tissue architecture ( for example of T and B cells in different areas of lymph nodes) - Leukocyte migration

Question 43

Where are complement proteins located?

Answer 43

Present in the plasma in inactive forms

Question 44

What are the 3 main functions of complement proteins?

Answer 44

- Inflammation - Opsonation and phagocytosis - Cell lysis

Question 45

What part of complement leads to chemotaxis and stimulates the lipoxygenase pathway ?

Answer 45

C5a

Question 46

What part of complement promotes phagocytosis by neutrophils and macrophages?

Answer 46

C3b

Question 47

What part of complement contributes to cell lysis?

Answer 47

MAC complex (C5b-C9)

Question 48

Give an example of a complement inhibitor?

Answer 48

Anti-C5 antibody (Eculizimab)

Question 49

What are mediators of chronic inflammation

Answer 49

Cytokines

Question 50

What cytokines result in the termination of immune response and induction of tissue repair and fibrosis?

Answer 50

TGF-B and IL-10