Chronic inflammation

Question 1

What are the causes of chronic inflammation?

Answer 1

• persistent infections
• allergies
• autoimmunity
• co-morbidities: T2DM, atherosclerosis, Alzheimers
• inflammation against endogenous substances e.g. cholesterol, urate

Question 2

What immune cells are typically involved in chronic inflammation?

Answer 2

• adaptive immune cells

macrophages, lymphocytes

Question 3

What are the mechanisms underlying tissue damage and altered function in chronic inflammation?

Answer 3

• necrosis
• fibrosis
• scarring
• collagen deposition
• angiogenesis

Question 4

What is the histological marker of chronic inflammation?

Answer 4

• hyperchromatic nuclei
• disordered structure
• fibrosis
• altered anatomy

Question 5

Which chemical mediators are active in chronic inflammation?

Answer 5

adaptive cytokines

e/g/ TFNa and IFNg

Question 6

What are the main features of macrophages in chronic inflammation?

Answer 6

• act as sentinels
• derive from monocytes in blood
  phagocytes
  activate other cells
  secrete inflammatory cytokines (IL-1, TNFa)
  produce growth factors for tissue repair
  lead to tissue destruction in chronic inflammation

Question 7

What are the main features of lymphocytes in chronic inflammation?

Answer 7

• granulomatous inflammation, autoimmunity, allergy
• recruited by TNFa, IL-1 (from mQ)
• Activate B cell sand mQ

Question 8

What are the 3 signals that propagate chronic inflammation following T cell: mQ interaction?

Answer 8

• (Tcell) CD40L - CD40 (mQ)
• TCR: MHC-peptide
• IFNg secreted by T cell to act on infected mQ

Question 9

What are the auxiliary immune cells involved in chronic inflammation?

Answer 9

• eosinophils
• mast cells
• neutrophils

Question 10

What types of chronic inflammation do neutrophils get recruited to?

Answer 10

suppurative inflammation (abscess, osteomyelitis)

recruited by IL-8

neutrophil-rich infiltrate is called ‘Acute on chronic inflammation’

Question 11

What are the types of chronic inflammation?

Answer 11

• non-specific
• autoimmune
• chronic suppurative
• chronic granulomatous

Question 12

What is non-specific chronic inflammation?

Answer 12

= when acute inflammation fails to eradicate causal agent

• tissue destruction
• ulcers
• ischaemic necrosis
  e. g. H. pylori

Question 13

What is autoimmune chronic inflammation?

Answer 13

= immune response to self antigens

• complex mechanisms
• insidious
• progressive and persistent

Question 14

What is suppurative chronic inflammation?

Answer 14

= persisting suppurative inflammation

starts as acute purulent inflammatio, which accumulates as an abscess

Question 15

What is suppurative inflammation?

Answer 15

= pus-forming

= purulent

Question 16

What is an abscess?

Answer 16

• fibrosis walls off a focus of acute inflammation
  = localised collection of purulent inflammation
• pyrogenic bacteria
• central necrotic area
• may need to be laid open and allowed to heal

Question 17

What is chronic granulomatous inflammation?

Answer 17

= develops when causative agent cannot be eliminated

granuloma: prevents spread of infection, contain:
- mQ
- lymphocytes
- fibroblasts
- necrotic tissue

Question 18

What are the different types of granuloma?

Answer 18

• immune (infection or autoimmune)
• foreign body
• disease of unknown cause (eg sarcoidosis)

Question 19

What are epitheloid cells?

Answer 19

activated mQ that have undergone changes in appearance

= increased cytoplasm, look like epithelial cells

Question 20

What is the gross microscopic appearance of a granuloma?

Answer 20

CENTRE
cluster of activated mQ (epitheloid)

PERIPHERY
rim of lymphocytes, fibroblasts and connective tissue

Question 21

What is another name for multinucleated giant cells?

Answer 21

Langhans giant cells

Question 22

What are the outcomes of granulomatous inflammation?

Answer 22

• causative agent eradicated (+ tissue healing)

- causative agent persists (granuloma may be calcified over time)

Question 23

What are the types of tissue repair?

Answer 23

• regeneration

- replacement (with connective tissue): scar/fibrosis

Question 24

What process is needed in order for tissue repair to occur?

Answer 24

inflammation

• needed for elimination of causative agent
• trigger for repair

Question 25

Which mQ have important roles in tissue repair?

Answer 25

M1
classically activated mQ
eliminate microbes and dead cells

M2
alternatively activated mQs
secrete growth factors
secrete cytokines 
trigger fibroblast proliferation and collagen synthesis at injured site

Question 26

What is PRIMARY INTENTION in wound healing?

Answer 26

• repair by regeneration

e. g. simple, clean unaffected wounds

Question 27

What is SECONDARY INTENTION in wound healing?

Answer 27

repair by regeneration and scarring

e.g. usually large wounds, abscess, ulcers etc
more complicated process

Question 28

in primary intention wound healing, what happens ~24hr after?

Answer 28

• neutrophil infiltration of wound

- proteolytic clearance of debris and microbes

Question 29

What happens ‘days’ after healing by primary intention?

Answer 29

day 2: migration and proliferation of epithelial cells at wound edges

day 3: mQ replaces neutrophils, invasion of granulation tissue

day 5: granulation tissue fills wound, angiogenesis and oedema

Question 30

What occurs in the later stages of healing by primary intention?

Answer 30

week 2: fibroblast proliferation
collagen deposition
vessel regression
scar blanching

month 1: 
scar with few inflammatory cells
normal epidermis
dermal appendages are lost permanently 
wound strength will recover to 80% of pre-injury

Question 31

What are the main types of abnormal tissue repair?

Answer 31

• wound dehiscence/rupture and ulceration
• hypertrophic scars and keloids
• excessive wound contraction