3. Chronic inflammation Flashcards
(21 cards)
What is chronic inflammation?
Chronic response to injury associated with fibrosis.
Why does chronic inflammation arise?
- secondary to acute inflammation
- arises ‘de novo’: some chronic infections (e.g. TB), some autoimmune conditions (e.g. RA), prolonged exposure to some toxic agents (e.g. silica)
- 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:
- Phagocytosis - not always as effective as neutrophils but better at destroying some difficult to kill bacteria such as M. tuberculosis
- Antigen presentation to immune system
- Secretion of numerous substances (esp. cytokines) that summon and activate other cells
- Induce fever, acute phase reaction and cachexia
Repair roles:
- Stimulate angiogenesis (important in wound healing)
- 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?
- Eosinophils : normally scattered throughout body tissues but seen in large numbers in certain circumstances.
- Fibroblasts : respond to chemotatic stimuli, produce CT substances such as collagen, elastin and glucosaminoglycans.
- Myofibroblasts : differentiated fibroblasts that can contract, important in wound healing.
In which circumstances do eosinophil numbers increase?
- parasite infections
- some immune responses, e.g. in bronchi in asthma
- 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?
- Langhans giant cells
- nuclei arranged around periphery of cell (horseshoe)
- often (but not exclusively) seen in tuberculosis
- Foreign body giant cells
- nuclei arranged randomly in cell
- often (but not exclusively) seen when a hard to digest foreign body is present
- 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?
- 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
- 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.
- fibrosis (e.g. liver cirrhosis)
- impaired organ function (e.g. chronic inflammatory bowel disease) and atrophy (gastric mucosa)
- 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)
