Int 8: Inflammation

Question 1

What are some of the inducers/causes of inflammation after response to injury/trauma/exposure?

Answer 1

• Cell lysis
• Virulence factors (LPS, endotoxin, exotoxins, helminth proteases)
• PAMPs
• Cellular necrosis and release of intracellular contents
• Degradation of basement membrane
• Loss of epithelial or endothelial integrity

Question 2

What are some characteristic features of inflammation?

Answer 2

• Vasodilation (redness + heat)
• Increased vascular permeability (entry of plasma proteins such as antibodies, complement components etc to the site of infection)
• Leukocyte extravasation (white blood cells move into tissues (early = neutrophils, Later = monocytes and lymphocytes)
• Stimulation f immune response
• Loss of function

Question 3

Main components of the inflammatory response?

Answer 3

• Mast cells: release granules of inflammatory mediators (histamine)
• Mononuclear phagocytes: phagocytosis and production of pro-inflammatory cytokines
• Neutrophils: phagocytes and proteases
• T-lymphocytes: helper cells
• Platelets
• NK cells
• Fibroblasts, epithelial and endothelial cells
• Vasoactive mediators (histamine)
• Lipid mediators (prostaglandins)
• Proteins

Question 4

What signals are Mast cells activated by? (hint = C)

Answer 4

C3a and C5a and DAMPs

Question 5

When activated, mast cells release a variety of compounds that contribute to inflammation:

a) Histamines
b) Prostaglandins and Leukotrienes
c) Cytokines

What do all the above chemicals do?

Answer 5

a) Dilation of blood vessels and increase their permeability
b) Lipid mediators. Prostaglandin induces vasodilation, enhances permeability and helps recruit immune cells. Leukotrienes are potent chemotactic chemicals that attract other immune cells to the site of infection/damage
c) TFN-alpha, IL-1, IL-6. Amplify and sustain inflammatory response

Question 6

Label which of the following is true of either Prostaglandins or Leukotrienes:

a) Generated from arachidonic acid by cyclo-oxygenase 1 (Cox-1) and cyclo-oxygenase 2 (Cox-2).
b) Short half life
c) Chemotactic factors for neutrophils and macrophages
d) Stimulate proliferation and cytokine release in macrophages
e) Powerful vasodilators
f) Potentiate vasoactive mediators
g) Increase adhesion molecules and toxic oxygen products in neutrophils
h) Pyrogenic
i) Generated from arachidonic acid by 5-lipoxygenase

Answer 6

a) Prostaglandins
b) Prostaglandins
c) Leukotrienes
d) Leukotrienes
e) Prostaglandins
f) Prostaglandins
g) Leukotrienes
h) Prostaglandins
i) Leukotrienes

Question 7

How does inflammation cause a) pain and b) fever?

Answer 7

PAIN:
- Inflammatory mediators affect nociceptors
- Bradykinin causes pain
- Exudation of plasma increases tissue pressure

FEVER:
- Increase of body temp so defenses work better
- Acts on hypothalamus - increase in heat production and retention

Question 8

Inflammation can be resolved by pro/resolution/repair mediators. An exampleof these are Lipoxins and Resolvins that are secreted by macrophages, neutrophils and structural cells. What are 5 of their main functions.

Answer 8

• Reduce diapedesis
• Reduce neutrophil chemotaxis
• Production of pro-inflammatory cytokines
• Vascular permeability
• Initiate phagocytosis of apoptotic neutrophils

Question 9

Another example of pro-resolution/repair mediators is TGF-Beta secreted by M2 macrophages. One of its main functions is to mediate wound healing. Give 4 mechanisms through which it does this?

Answer 9

• Angiogenesis
• Fibroblast proliferation
• Collagen synthesis
• Remodelling of the ECM

TGF-Beta is also a potent inhibitor of pro-inflammatory macrophage activation

Question 10

Efferocytosis is the a)________ of apoptotic cells by b)_________. This is aided by neutrophils that let out signals such as ‘find-me’, ‘keep out’, or ‘eat me’. which helps phagocytes decipher between viable/apoptotic cells

Answer 10

a) Clearance
b) Phagocytosis