Chronic inflammation Flashcards
What are the causes of chronic inflammation?
- persistent infections
- allergies
- autoimmunity
- co-morbidities: T2DM, atherosclerosis, Alzheimers
- inflammation against endogenous substances e.g. cholesterol, urate
What immune cells are typically involved in chronic inflammation?
- adaptive immune cells
macrophages, lymphocytes
What are the mechanisms underlying tissue damage and altered function in chronic inflammation?
- necrosis
- fibrosis
- scarring
- collagen deposition
- angiogenesis
What is the histological marker of chronic inflammation?
- hyperchromatic nuclei
- disordered structure
- fibrosis
- altered anatomy
Which chemical mediators are active in chronic inflammation?
adaptive cytokines
e/g/ TFNa and IFNg
What are the main features of macrophages in chronic inflammation?
- 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
What are the main features of lymphocytes in chronic inflammation?
- granulomatous inflammation, autoimmunity, allergy
- recruited by TNFa, IL-1 (from mQ)
- Activate B cell sand mQ
What are the 3 signals that propagate chronic inflammation following T cell: mQ interaction?
- (Tcell) CD40L - CD40 (mQ)
- TCR: MHC-peptide
- IFNg secreted by T cell to act on infected mQ
What are the auxiliary immune cells involved in chronic inflammation?
- eosinophils
- mast cells
- neutrophils
What types of chronic inflammation do neutrophils get recruited to?
suppurative inflammation (abscess, osteomyelitis)
recruited by IL-8
neutrophil-rich infiltrate is called ‘Acute on chronic inflammation’
What are the types of chronic inflammation?
- non-specific
- autoimmune
- chronic suppurative
- chronic granulomatous
What is non-specific chronic inflammation?
= when acute inflammation fails to eradicate causal agent
- tissue destruction
- ulcers
- ischaemic necrosis
e. g. H. pylori
What is autoimmune chronic inflammation?
= immune response to self antigens
- complex mechanisms
- insidious
- progressive and persistent
What is suppurative chronic inflammation?
= persisting suppurative inflammation
starts as acute purulent inflammatio, which accumulates as an abscess
What is suppurative inflammation?
= pus-forming
= purulent
What is an abscess?
- 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
What is chronic granulomatous inflammation?
= develops when causative agent cannot be eliminated
granuloma: prevents spread of infection, contain:
- mQ
- lymphocytes
- fibroblasts
- necrotic tissue
What are the different types of granuloma?
- immune (infection or autoimmune)
- foreign body
- disease of unknown cause (eg sarcoidosis)
What are epitheloid cells?
activated mQ that have undergone changes in appearance
= increased cytoplasm, look like epithelial cells
What is the gross microscopic appearance of a granuloma?
CENTRE
cluster of activated mQ (epitheloid)
PERIPHERY
rim of lymphocytes, fibroblasts and connective tissue
What is another name for multinucleated giant cells?
Langhans giant cells
What are the outcomes of granulomatous inflammation?
- causative agent eradicated (+ tissue healing)
- causative agent persists (granuloma may be calcified over time)
What are the types of tissue repair?
- regeneration
- replacement (with connective tissue): scar/fibrosis
What process is needed in order for tissue repair to occur?
inflammation
- needed for elimination of causative agent
- trigger for repair
Which mQ have important roles in tissue repair?
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
What is PRIMARY INTENTION in wound healing?
- repair by regeneration
e. g. simple, clean unaffected wounds
What is SECONDARY INTENTION in wound healing?
repair by regeneration and scarring
e.g. usually large wounds, abscess, ulcers etc
more complicated process
in primary intention wound healing, what happens ~24hr after?
- neutrophil infiltration of wound
- proteolytic clearance of debris and microbes
What happens ‘days’ after healing by primary intention?
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
What occurs in the later stages of healing by primary intention?
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
What are the main types of abnormal tissue repair?
- wound dehiscence/rupture and ulceration
- hypertrophic scars and keloids
- excessive wound contraction
