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What is chronic inflammation?

Chronic response to injury associated with fibrosis.


Why does chronic inflammation arise?

1. secondary to acute inflammation
2. arises 'de novo': some chronic infections (e.g. TB), some autoimmune conditions (e.g. RA), prolonged exposure to some toxic agents (e.g. silica)
3. develops alongside/superimposed on acute inflammation


What are the major cell types in chronic inflammation? How is this different to acute inflammation?

Major cell types = macrophages and lymphocytes.

In acute inflammation, neutrophils are predominant.


Which new tissue type arises in chronic inflammation?

granulation tissue


Describe the lifecycle of a macrophage.

i) Monocytes made in BM and circulate in blood for ~6 days.
ii) Enter tissues - i.e. are now macrophages - and become dormant until activated by local challenge.
iii) Live for many months and can replicate (unlike neutrophils).


Name 6 functions of macrophages.

Defensive roles:
1. Phagocytosis - not always as effective as neutrophils but better at destroying some difficult to kill bacteria such as M. tuberculosis
2. Antigen presentation to immune system
3. Secretion of numerous substances (esp. cytokines) that summon and activate other cells
4. Induce fever, acute phase reaction and cachexia

Repair roles:
5. Stimulate angiogenesis (important in wound healing)
6. Induce fibrosis


What are the functions of lymphocytes in chronic inflammation?

- B cells: differentiate into plasma cells for antibody production
- T cells: cytotoxic effect on virus-infected cells and tumour cells

+ cytokine secretion to influence other inflammatory cells


Apart from macrophages and lymphocytes, which cells are seen in chronic inflammation?

1. Eosinophils : normally scattered throughout body tissues but seen in large numbers in certain circumstances.

2. Fibroblasts : respond to chemotatic stimuli, produce CT substances such as collagen, elastin and glucosaminoglycans.

3. Myofibroblasts : differentiated fibroblasts that can contract, important in wound healing.


In which circumstances do eosinophil numbers increase?

1. parasite infections
2. some immune responses, e.g. in bronchi in asthma
3. some tumours, e.g. Hodgkin's lymphoma


What are giant cells and when are these seen?

Fusion of macrophages to produce very large single cells - contain dozens to 100s of nuclei. Represents frustrated phagocytosis.

Seen in granulomatous inflammation.


What are the 3 types of giant cell and when are these specifically seen?

1. Langhans giant cells
- nuclei arranged around periphery of cell (horseshoe)
- often (but not exclusively) seen in tuberculosis

2. Foreign body giant cells
- nuclei arranged randomly in cell
- often (but not exclusively) seen when a hard to digest foreign body is present

3. Touton giant cells
- nuclei arranged in ring towards centre of cell
- form in lesions where there is a high lipid content, e.g. fat necrosis and xanthomas


How do chronic inflammation and the immune system overlap?

1- Immune diseases can cause pathology by chronic inflammation, e.g. RA, viral hepatitis

2- Chronic inflammatory processes can stimulate immune responses


What is granulomatous inflammation?

Type of chronic inflammation in which granulomas are seen.


What are granulomas?

- Aggregations of chronic inflammatory cells (0.5-1 mm diameter) that form around particles that are poorly soluble or difficult to eliminate, e.g. splinters, 'tough' bacteria such as M. tuberculosis.
- Particles can be free or phagocytosed within centre of granuloma - are walled off, concentrated with mononuclear cells


What are epithelioid cells?

Macrophages modified to look like epithelial cells - are elongated, have eosinophilic cytoplasm and appear tightly packed.


What are the 2 general types of granulomas?

1. Foreign body granulomas:
- develop around material that is not antigenic, e.g. surgical thread
- contain macrophages, foreign body giant cells, epithelioid cells and some fibroblasts (at the periphery)
- very few, if any, lymphocytes

2. Hypersensitivity or immune type granulomas
- develop around insoluble but antigenic particles that cause cell-mediated immunity, e.g. tuberculosis, leprosy, fungi
- contain macrophages, giant cells (may be of Laghans type), epithelioid cells (usually more prominent than in foreign body granulomas), some fibroblasts (at periphery) and lympocytes
- can undergo central necrosis (particularly seen in granulomas associated with TB)


Give 3 examples of diseases in which hypersensitivity/immune-type granulomas are seen.

Diseases with unknown aetiology:
i. sarcoidosis - granulomas are seen in organs throughout body
ii. Crohn's disease (50% cases)
iii. Wegener's granulomatosis


Why can hypersensitivity/immune-type granulomas be harmful?

Occupy parenchymal space within an organ.


Name 3 possible complications of chronic inflammation.

1. fibrosis (e.g. liver cirrhosis)
2. impaired organ function (e.g. chronic inflammatory bowel disease) and atrophy (gastric mucosa)
3. stimulation of immune response


What is fibrosis?

Excess of fibrous tissue that occurs when fibroblasts are stimulated by cytokines to produce excess collagen - typically seen in chronic inflammation.


Why is fibrosis initially helpful, but harmful if it is excessive/inappropriate?

Collagen production initially helpful in chronic inflammation as:
- helps wall off infected area
- production of fibrous scar to replace damaged tissue essential in wound healing

But if excessive/inappropriate, can:
- replace normal parenchymal tissue and impair organ function
- if area of fibrosis contains enough myofibroblasts, can slowly contract and cause further problems (e.g. contraction of cirrhotic liver will impair flow of portal blood, resulting is ascites)