Acute Inflammation-Mediators

Question 1

The most important mediators of acute inflammation are:

Answer 1

1. Vasoactive amines
2. Prostaglandins and leukotrienes(lipid products)
3. Chemokines
4. Products of complement activation

Question 2

Cell-derived mediators are produced by cells that detect invaders and damage in tissues

True or false
Give examples of such cells

Answer 2

Macrophages 
Dendritic cells
Mast cells 
Platelets 
Neutrophils

Question 3

The cell-derived mediators of inflammation can be classified into:

Answer 3

Primary/Preformed- secluded in the intercellular granules of leukocytes and released during inflammation eg histamine in mast cells

Secondary/Newly synthesized-produced de novo eg prostaglandins, leukotrienes, cytokines

Question 4

Plasma derived mediators are produced in the liver and are activated by proteolytic cleavages

Give an example

Answer 4

Products of complement system

Question 5

Mention 8 cell-derived mediators of inflammation, their principal sources and their actions

Answer 5

•Histamine, from:
mast cells
basophils
platelets
•Function: 
vasodilation
⬆️vascular permeability 
Endothelial activation 

•Serotonin, from:
Platelets
•Function:
Vasoconstriction 
⬆️vascular permeability 

•Prostaglandins, from:
Mast cells
Leukocytes 
•Functions:
Pain 
Fever
Vasodilation 

•Leukotrienes, from:
Mast cells
Leukocytes 
•Functions:
⬆️vascular permeability 
Chemotaxis 
Leukocyte adhesion and activation 

•PAF, from: 
Leukocytes 
Mast cells 
•Functions:
Vasodilation 
⬆️vascular permeability 
Leukocyte adhesion 
Chemotaxis 
Degranulation 
Oxidative burst 

•Nitric oxide, from:
Endothelium 
Macrophages 
•Functions:
Vascular smooth muscle relaxation 
Killing of microbes 

•Cytokines(TNF, IL-1), from:
Macrophages
Endothelial cells
Mast cells 
•Functions:
Endothelial activation
Fever/pain/anorexia/hypotension 
⬇️vascular resistance 

•Chemokines, from: 
Leukocytes 
Activated macrophages 
•Functions: 
Chemotaxis 
Leukocyte activation

Question 6

Mention plasma-derived mediators of inflammation, their principal sources and actions

Answer 6

•Complement products, from:
Plasma
•Functions
Leukocyte chemotaxis and activation 
Vasodilation 
Mast cell stimulation 

•Kinins, from: 
Plasma 
•Functions
⬆️Vascular permeability 
Smooth muscle contraction 
Vasodilation 
Pain

Question 7

Histamine is released by mast cell degradation in response to:

Answer 7

1. Trauma
2. Binding of antibodies to mast cells
3. Products of complement system(C3a and C5a)

Question 8

The lipid mediators of acute inflammation are produced from❓

Answer 8

Arachidonic acid, in membrane phospholipids through the action of phospholipases(phospholipase A2) activated by ⬆️cytoplasmic Ca2+

AA is gotten from dietary sources or from conversion of linoleic acid

Question 9

Mention AA-derived mediators and their functions

Answer 9

Increased intracellular Ca2+
⬇️Phospholipases
Arachidonic acid
⬇️ OR ⬇️ *
5-lipoxygenase 12-lipoxygenase
⬇️ ⬇️
Leukotrienes Lipoxins
⬇️ ⬇️
Vasoconstriction Vasodilation
Bronchospasm ❌Chemotaxis
⬆️permeability Monocyte adhesion

                      *OR
                       ⬇️
            Cyclooxygenase 
                      ⬇️
                 Prostaglandin
          ⬇️                           ⬇️
Prostacyclin           Thromboxane A2
          ⬇️                           ⬇️
 Vasodilation            Vasoconstriction  ❌platelet aggregation        Opp. 

•PGD, PDE, PGF
Vasodilation
Edema

Question 10

Cyclooxygenase inhibitors❓

Answer 10

NSAID eg Ibuprofen, used in the treatment of pain and fever

Question 11

5-lipoxygenase inhibitors❓

Answer 11

Used in inhibiting formation of leukotrienes Eg Zileuton

Useful in asthma treatment, along with leukotriene receptor antagonists eg Montelukast

Question 12

Anti-inflammatory agents?

Answer 12

Corticosteroids

Inhibit phospholipases

Question 13

Mention the functions of the cytokines you know

Answer 13

Endothelial activation
Leukocyte activation
Systemic acute phase response

TNF:
Leukocyte recruitment
Leukocyte adhesion to endothelium
Leukocyte migration through vessels

IL-1:
Stimulates expression of endothelial adhesion molecules
Emigration of neutrophils and macrophages
Fever

Question 14

Where are cytokines produced?

What are their antagonists useful in treating?

Answer 14

By activated dendritic cells and macrophages

Chronic inflammatory diseases eg rheumatoid arthritis and psoriasis

Question 15

The complement pathway is made up of 3 parts❓

What is the end of this pathway❓

Answer 15

Classical: triggered by C1 to antibody (IgM/IgG) that is bound to an antigen

Alternate: triggered by microbial surface protein (no antigen)

Lectin: triggered when pectin binds to carbohydrates on microbes and activates C1

•To create the membrane-attack system(C5b-9)

Question 16

The critical step in complement activation is which❓

Answer 16

The proteolysis of the third and almost abundant component, C3

Question 17

C3a and C5a (anaphylatoxins) stimulate histamine release from mast cells

True/false
What effect does that have?

Answer 17

True

Vasodilation
⬆️vascular permeability

Question 18

Which product of the complement system activates the lipoxygenase pathway of AA

Answer 18

C5a

Question 19

Which product of the complement system act as an opsonin and promotes phagocytosis by neutrophils and macrophages❓

Answer 19

C3b C3b

Question 20

Which product of the complement system increase permeability of cells to water and ions and eventually death❓

Answer 20

Membrane attack complex

Question 21

Regulatory proteins of the complement system❓

Answer 21

C1 inhibitor: inherited deficiency is the cause of hereditary angioedema

Decay Accelerating Factor and CD59: proteins linked to plasma membranes by (glycophosphatidyl inositol) GPI anchor

DAF prevents formation of C3 convertase
CD59 prevents formation of MAC

Mutation of enzyme that produces GPI anchor results in PNH

Question 22

Functions of PAF

Answer 22

Vasoconstriction

At low conc.:
Vasodilation
⬆️vascular permeability

Question 23

Describe the production, degradation and function of bradykinin

Answer 23

Kinin—Kininogen—braydikinin by kallikrein

Functions of bradykinin 
Contraction of smooth muscle 
Permeability of smooth muscle 
Pain when injected into skin
Dilation of blood vessels

Kininase deactives