chronic inflammation

Question 1

What is chronic inflammation?

Answer 1

Inflammation, repair and tissue destruction occurring simultaneously
Much more significant tissue destruction than acute
Frustrated healing
Prolonged (weeks/months/years)
Comes on much slower
Systemic features (fever, malaise) less than acute

Question 2

What causes chronic inflam?

Answer 2

1. Result of previous acute inflam due to injurious agent (grit, suture etc) remaining
   Poor healing due to inadequate blood supply
2. Chronic and low grade from outset- certain microorganisms (eg. Mycobacteria for TB), prolonged exposure to toxins (eg. Silica for silicosis or lipids in plasma [atherosclerosis]) OR autoimmune disease (eg. Rheumatoid arthritis)

Question 3

What are features of chronic inflam?

Answer 3

Minimal vascular changes

Infiltration by chronic inflammatory cells (macrophages, lymphocytes, plasma cells [looks like fried egg])

Ongoing repair- vascular granulation tissue (fibroblasts and endothelial cells) may mature to give scarring

Continued tissue destruction- inflammatory agent/cells

Question 4

What are macrophages?

Answer 4

Derived from blood monocytes
Activated by Interferon-gamma (IFN-y produced by T cells)

M1 inv. in phagocytosis,
antigen presentation (stimulates immune response),
produce cytokines/chemokines (attract inflam cells and regulate inflam response),
produce growth factors and stimulate fibroblasts and endo cells for healing (M2)

Question 5

What are the interactions between immune cells?

Answer 5

Macrophage activate T cells however continuous feedback loop as T cells release cytokines (INF-y) to activate macrophages

Cytotoxic T cells kill virally infected and cancer cells
T helper cells activate B cells->plasma cells that produce antibodies

Macrophages and lymphocytes (T and B cells) release cytokines that help continue this response

Question 6

What are eosinophils?

Answer 6

Resemble neutrophils but have eosinophilic/pink cytoplasm containing pink granules w major basic proteins in
Important in parasitic infections (eg. Malaria, amoebiasis)
Can be toxic to epithelial cells

Question 7

Why is there tissue destruction?

Answer 7

Products of activated macrophages- free oxygen radicals, proteases

Necrotic tissue promotes further inflam

Neutrophils release enzymes

Cytotoxic T cells

Microorganisms release toxins

Question 8

How does repair occur?

Answer 8

1. Regeneration- complete resolution to normal tissue
2. Connective tissue deposition and scar formation- some tissues not capable of complete regeneration OR prolonged, severe damage
   Fibrosis stimulated by the cytokine- transforming growth factor beta (TGF-beta) by macrophages
   Angiogenesis- formation of new blood vessels by vascular endothelial growth factor
   Formation of granulation tissue (3-5days after injury)- made by fibroblasts making collagen and endothelial cells
   Remodelled so less endothelial cells and more collagen

Question 9

What is granulomatous inflam?

Answer 9

Distinct pattern of chronic inflam
Formation of granulomas (collection of multinucleate giant cells and epithelioid macrophages surrounded by rim of lymphocytes)
Can be diffuse or focal

Question 10

What are the types of giant cells?

Answer 10

Foreign body type- macrophages fused together but nuclei in haphazard pattern (eg. Sutures)

Langhans type- nuclei are around edge like horse shoe (often TB)

Question 11

What is the immune response in TB?

Answer 11

Cell mediated immune response T- helper 1 produces cytokines (INF-y) to activate macrophages which activate T-cells
This continued response (hypersensitivity) forms a granuloma

Often necrosis in centre of granuloma due to hypoxia and free oxygen radicals (central caseation)