Inflammation

Question 1

What is inflammation a response to?

Answer 1

Cellular injury

Question 2

What are the four main signs of acute inflammation?

Answer 2

Redness

Swelling

Pain

Heat

Question 3

What are the causes of inflammation?

Answer 3

Pathogens

Allergens

Auto-antigens

Physical damage

Extreme temperatures

Non-apoptosis cell death

Question 4

What happens in acute inflammation?

Answer 4

Change in local blood flow

Structural changes in the microvasculature

Recruitment/accumulation of immune cells and proteins

Question 5

What happens in the first stage of acute inflammation?

Answer 5

Steady state

Question 6

What happens in the second stage (damage) of acute inflammation?

Answer 6

1. Inflammatory signals
2. Vasodilators released
3. Vascular chnage

Question 7

What are the inflammatory signals in acute inflammation?

Answer 7

Non-apoptotic cell death

Detection of foreign material

Question 8

What vasodilators are released in acute inflammation?

Answer 8

Histamine

Nitric oxide

Question 9

Wha are the vascular changes in acute inflammation?

Answer 9

Increased permeability

Dilation

Reduced flow

Plasma leakage

Question 10

What benefits does increased vascular permeability and leakage bring?

Answer 10

Rapid movement of antibodies into site of inflammation specific to intruding pathogen

Recruiting proteins into tissue site —> increased activation of immune cells and source of protein for tissue repair

Recruitment of leukocytes

Formation of a physical barrier

Question 11

What is exudate?

Answer 11

Fluid, proteins and cells that have seeped out of a blood vessel

Question 12

What is the purpose of exudate?

Answer 12

Form separation between healthy and inflamed tissue
—> prevent inflammatory stimuli and pathogens from migrating into healthy tissue and causing further damage

Question 13

What happens in the third stage (immune cell recruitment) of acute inflammation?

Answer 13

Recruitment of inflammation signals at site of damage

These chemokines diffuse out to form a gradient

Leukocytes expressing complimentary chemokine receptors migrate towards the chemokine source

Question 14

What is an example of immune cell recruitment?

Answer 14

Chemokine: CXCL8 —> IL-8

Receptors: CXCR1 and CXCR2, g coupled 7-transmembrane proteins

Cell type: neutrophils

Question 15

How does neutrophil extravasation work?

Answer 15

1. Chemo-attraction
2. Rolling adhesion
3. Tight adhesion
4. Transmigration

Question 16

What happens in chemo-attraction in neutrophil extravasation?

Answer 16

Cytokines act on endothelial layer to promote upregulation of adhesion molecules

Question 17

What happens in rolling adhesion in neutrophil extravasation?

Answer 17

Carbohydrate ligands in a low affinity state on neutrophils bind selectins and migrate along blood vessel

Question 18

What happens in tight adhesion in neutrophil extravasation?

Answer 18

Chemokines promote low to high affinity switch in integrins —> enhance binding ti ligands

Question 19

What happens in transmigration in neutrophil extravasation?

Answer 19

Cytoskeletal rearrangement and extension of pseudopodia to move cell into interstitium

—> mediated by PECAM interactions on both cells

Question 20

What is neutrophil function at the site of inflammation?

Answer 20

1. Pathogen recognition
2. Pathogen clearance
   —> phagocytosis
   —> netosis —> take DNA out —> trap bacteria in ‘net’ —> allow macrophage to be recruited
3. Cytokine secretion
   —> recruitment and activation of other immune cells

Question 21

What happens in resolution of acute inflammation?

Answer 21

1. Pathogen recognition
   —> immune cells and antimicrobials will recognise infections/particulates
2. Short half life
3. Macrophages
   —> clear apoptosis cells
   —> produce inflammatory mediators
4. Repair/wounding healing

Question 22

What is persistent inflammatory stimuli?

Answer 22

Persistent/prolonged infection

Persistent toxic stimuli —> e.g allergens, pollutants

Unclearable particulates

Autoimmunity

Question 23

What does distinct immune cell infiltrate include?

Answer 23

Inflammatory macrophages

T cells

Plasma

Question 24

What are the good effects of macrophages?

Answer 24

Phagocytic

Cytotoxic

Anti-inflammatory

Wound repair

Question 25

What are the bad effects of macrophages?

Answer 25

Cytotoxic

Inflammatory

Pro-fibrotic

Question 26

What do T cells do in chronic inflammation?

Answer 26

Pro-inflammatory

Cytotoxic

Regulatory

Question 27

What do B cells do in chronic inflammation?

Answer 27

Generate plasma cells —> secrete antibody

Protective, clearing infection

Inflammatory —> driving reaction against self

Can be local to inflammatory site or operate remotely

Question 28

What is granulomatous inflammation?

Answer 28

Chronic inflammation with distinct pattern of granular formation

Triggered by strong T cell responses

Form against resistant agents

Question 29

What is a granuloma?

Answer 29

Aggregation of activated macrophages —> barrier designed for clearance

Question 30

What are the positive outcomes of acute and chronic inflammation?

Answer 30

Clear inflammatory agent

Remove damages cells

Restore normal tissue function

Question 31

What are the negative outcomes of acute and chronic inflammation?

Answer 31

Excess tissue damage

Scarring

Loss of organ function —> organ failure