Inflammation

Question 1

What is inflammation?

Answer 1

A rapid, non-specific response to cellular injury

Question 2

What are the 4 signs of inflammation?

Answer 2

Swelling (tumor)
Pain (dollor)
Redness (Rubor)
Heat (calor)

Question 3

What causes chronic inflammation?

Answer 3

Caused by persistent inflammatory stimuli e.g.:

• persistent/ prolonged infection
• persistent toxic stimuli
• unclearable particulates
• autoimmunity

Question 4

What kind of cells are present in chronic inflammation?

Answer 4

Macrophages
T cells and other lymphocytes
Plasma cells

Question 5

What is granulomatous inflammation?

Answer 5

Chronic inflammation with a distinct pattern of granuloma formation
Aggregation of activated macrophages
Triggered by strong T cell responses

Question 6

What is the role of macrophages in inflammation?

Answer 6

Recruited as monocytes to the site of inflammation but are also tissue resistant

Pros: phagocytic, cytotoxic, anti-inflammatory and can repair wounds

Cons: cytotoxic, inflammatory and pro-fibrotic

Question 7

What are qualities of T cells in inflammation?

Answer 7

Pro- inflammatory e.g. TNF
Cytotoxic
Regulatory- control immune system

Question 8

What are qualities of B cells in inflammation?

Answer 8

Generate plasma cells
Protective, clear infection
Inflammatory
Can be local or remote

Question 9

What are differences between acute and chronic inflammation?

Answer 9

Acute is immediate and lasts a few days whereas chromic is delayed and may last months or years

In acute neutrophils are predominant whereas in chronic macrophages are predominant

In acute histamine are released wheras in chronic there is ongoing cytokine release

In acute there’s prominent necrosis whereas in chronic there’s prominent scaring

Question 10

What are long- term outcomes of inflammation?

Answer 10

PROS: clears inflammatory agent, removes damaged cells, regain normal tissue function

CONS: excess tissue damage, scarring, loss of tissue function, ECM deposition, broncho-pseudomonia

Question 11

What is the first step of acute inflammation?

Answer 11

Inflammatory signals

Non-apoptotic cell death, detection of PAMPS and DAMPS by PRRs

Question 12

What are PAMPS, DAMPS and PRRs

Answer 12

PAMPS= pathogen associated molecular patterns e.g. peptidoglycan
DAMPS= damage associated molecular patterns (released when plasma membrane injured or cell dies)
PRRs= pathogen recognition receptors

Question 13

What is the second step of acute inflammation?

Answer 13

Vasodilators released

Histamine and nitric oxide

Question 14

What is histamine secreted from and what does it do?

Answer 14

From mast cells, basophils and platelets

Causes vasodilation, increased vascular permeability and endothelial activation

Question 15

What is the third step of acute inflammation?

Answer 15

Vascular changes

Increased permeability, dilation, reduced flow, plasma leakage

Question 16

What is the last step of acute inflammation?

Answer 16

Immune cell recruitment
Chemokine produced at site of damage, diffuse to form gradient. WBCs (neutrophils and macrophages) with complimentary receptors migrate towards source

Question 17

What are chemokine secreted by and what is their role?

Answer 17

From activated macrophages- involved in chemotaxis, leukocyte activation

Question 18

Whats the importance of neutrophils?

Answer 18

Often first cel type recruited to site of inflammation

Question 19

What soluble mediators are released at injury?

Answer 19

Histamine
Chemokines
Prostoglandins
Cytokines
Compliment proteins

Question 20

What are prostaglandins secreted from and what do they do?

Answer 20

come from mast cells and leukocytes. Cause vasodilation, pain and fevers

Question 21

What are cytokines secreted from and what do they do?

Answer 21

Main source is macrophages, endothelial cells, mast cells

Cause endothelial activation, fever, malaise, pain, anorexia, shock

Question 22

What are compliment proteins secreted from and what do they do?

Answer 22

Main source is plasma (made in liver)

Actions involve chemotaxis and activation, vasodilation,, opsonisation

Question 23

How do neutrophils get from blood vessels to the site of inflammation?

Answer 23

By neutrophil extravasion

1. Chemo-attraction : cytokines- endothelial up regulation of adhesion molecules like selectins
2. Rolling adhesion: Carbohydrate ligands on neutrophils bind selectins (on endothelia) with low affinity
3. Tight adhesion: chemokines promote switch from low to high affinity integrins to enhance binding of ligands e.g. ICAM1
4. Diapadesis (exit) and Transmigration: cytoskeletal rearrangement and extension of pseudopodia, mediated by PECAM interactions on both cells- so neutrophils reach inflammation site

Question 24

What is exudate?

Answer 24

Exudate is fluid, proteins and cells which have seeped out of blood vessels
Acts as a barrier between inflamed tissue and healthy tissue

Question 25

What is the function of neutrophils?

Answer 25

Pathogen recognition: use of TLR4 and CD14 to identify lipolysaccharides present on gram negative bacteria

Pathogen clearance: phagocytosis and netosis
Phagocytosis- large particels englufed in phagosomes with lysosome
Netosis- unique form of cell death characterised by release of decondensed chromatin and granular contents to extracellular space

Cytokine secretion: recruitment and activation of other immune cells

Question 26

What is the resolution of acute inflammation?

Answer 26

Pathogen recognition
Short half-life- neutrophils have short half life
Macrophages- clear apoptotic cells
Repair wound/ healing