Session 3: Chronic Inflammation Flashcards
Define chronic inflammation.
Chronic response to injury with associated fibrosis.
How does chronic inflammation arise?
It can take over from acute inflammation if the damage is too severe to be resolved within a few days. It can also arise de novo meaning it arises from the beginning. It may develop alongside of acute inflammation in severe persistent or repeated irritation.
How can chronic inflammation arise de novo?
Autoimmune conditions such as rheumatoid arthritis Chronic infections such as viral hepatitis Chronic low-level irritations Prolonged exposure to toxic agents
What cells are involved in chronic inflammation?
Macrophages Lymphocytes (Both T and B) Eosinophils Fibroblasts/myofibroblasts Giant cells
Where do macrophages come from?
Macrophages are called macrophages or histiocytes when they are in the tissue. In the blood they are called monocytes. Monocytes are produced by the bone marrow and circulate the blood for around 6 days before they enter tissue and become dormant until activated. They arrive after neutrophils and take over the roles that the neutrophils couldn’t do.
What are the roles of the macrophages?
Phagocytosis that isn’t always as effective as neutrophils’. But can be better at destroying some bacteria that neutrophils can’t. Secretion of numerous substances that summon and activate other cells by producing cytokines. Specifically cytokine called interleukin 1. Also produce blood clotting factors and proteases. Presenting antigens to the immune system and initiation of immune response. Stimulating angiogenesis important in wound healing. Inducing fibrosis Inducing fever, acute phase reaction and cachexia.
Give an example of a bacteria that macrophages are better at destroying than neutrophils.
Mycobacterium tuberculosis
What are the roles of the lymphocytes?
T-cell: Processing antigens and involved in control and some cytotoxic functions. Natural killer cells: Attack virus-infected cells and sometimes tumour cells as well. B-cells: Differentiate to plasma cells in order to secrete antibodies.
What are the roles of eosinophils?
Attack large parasites such as worms and present in high numbers in some immune responses like bronchi in asthma, some tumours like Hodgkin’s lymphoma. Basically involved in: Parasitic infection Tumours Allergic reactions
What are the roles of Fibroblasts and myofibroblasts?
Move to site where they are needed in response to chemotactic stimuli. Fibroblasts produce connective tissue such as collagen, elastin and GAGs. They can also differentiate into cells that can contract like myofibroblasts. Myofibroblasts are important in wound healing. However both can form scar tissue.
What types of giant cells are there?
Langhans giant cells Foreign body giant cells Touton giant cells Reed-Sternberg cells
How do giant cells form?
By the fusion of macrophages. they are very large and contain 10-100 nuclei.
Where are giant cells seen?
In granulomatous inflammation.
What are the roles of giant cells?
They usually form granulomas and do frustrated phagocytosis.
What are the features/roles of Langhans giant cells?
Nuclei are arranged around the periphery of the giant cell. Often seen in tuberculosis
What are the features/roles of Foreign body giant cells?
Nuclei are arranged randomly in the cell. Often seen when a hard to digest foreign body is present. Small foreign body: phagocytosed by the giant cell and seen within it. Large foreign body: The foreign body giant cell sticks to its surface
What are the features/roles of Touton giant cells?
Nuclei arranged in a ring towards the centre of the cell. Form in lesions where there is a high lipid content such as fat necrosis and xanthomas. Lesions will also contain cells called foam cells that sit on the periphery which are macrophages whose cytoplasm appears foamy as they have phagocytosed a lot of lipid.
Give some examples of possible complications of chronic inflammation.
- Tissue destruction
- Excessive fibrosis
- Imparied function
- Atrophy
- Stimulation of immune response
Explain fibrosis leading up to impaired function.
An excess of fibrous tissue.
Fibroblasts are stimulated by cytokines to produce excess collagen.
It is initially helpful to wall of infected areas and is essential in wound healing.
If it is excessive or inappropriate however it can replace normal parenchymal tissue.
This leads to impairment of organ function.
Myofibroblasts can also cause contraction seen in a cirrhotic liver which can obstruct blood flow through portals, sclerosis can also form.
Explain how chronic inflammation is a part of inappropriate immune response.
There is a macrophage to lymphocyte interaction where the macrophages first call the lymphocytes to appear and then lymphocytes can call for more macrophages leading to a viscious cycle.
Immune system is supposed to use inflammation as a non-specific weapon to destroy its targets. However the immune system might attack targets such as pollen or the body’s own tissue.
Pollen attack leads to allergy. Body’s own cells lead to autoimmune disease.
Define granulamatous inflammation.
A type of chronic inflammation in which granulomas are seen.
Explain what a granuloma is and its role.
The body’s way to deal with particles that are poorly soluble or difficult to eliminate.
E.g. thorns, splinters, mycobacterium tuberculosis, mycobacterium leprae.
A granuloma forms around the particle. It walls it off whilst concentrating mononuclear cells within its centre with which it hopes to destroy the particle.
Granulomas fall into two general types. Which?
Foreign body granulomas
Hypersensitivity or immune type granulomas
When are foreign body granulomas seen?
In the case of a foreign body entering the body that the rest of the immune system can’t handle.
It contains macrophages, foreign body ciant cells, epithelioid cells and fibroblasts.
It develops around material that is not antigenic.
