Next Lesson - Regeneration and Repair of Tissues
Core
There are several different ways chronic inflammation arises. These include:
- Taking over from acute inflammation.
- Developing alongside acute inflammation when the irritation is severe or persistent.
- De novo (from the start) - developing with no period of acute inflammation preceding it, for example, in autoimmune conditions.
These cells are derived from blood monocytes, although some tissue-resident macrophages come from fetal precursors and renew themselves locally. Their functions include:
- Phagocytosis and destruction of bacteria.
- Antigen presentation and therefore initiation of an immune response.
- Synthesis of cytokines (signalling proteins), complement components (blood proteins that help destroy microbes), blood clotting factors and proteases (enzymes that break down proteins).
- Control of other cells by cytokine release.
Image - Macrophages under a light microscope
Creative commons source by Librepath [CC BY-SA 4.0 (https://creativecommons.org/licenses/by-sa/4.0)]
There are two types of lymphocytes: B lymphocytes and T lymphocytes. The different types have different functions:
- B cells: produce and secrete antibodies by differentiating into plasma cells.
- T cells: kill virus-infected cells and sometimes tumour cells, and help to coordinate the immune response.
Image - Histological sample showing two lymphocytes
Creative commons source by Ed Uthman [CC BY-SA 4.0 (https://creativecommons.org/licenses/by-sa/4.0)]
These cells are seen in large numbers with atopic (allergic) sensitivity reactions such as asthma. They also attack large parasites such as worms and may be seen in association with some types of cancer, for example Hodgkin’s lymphoma (a cancer of the lymphatic system).
Image - Histological sample of an eosinophil
Creative commons source by Dr Graham Beards [CC BY-SA 4.0 (https://creativecommons.org/licenses/by-sa/4.0)]
These cells respond to chemotactic stimuli (chemical signals that attract cells) to move to the site where they are needed. They play a role in wound healing and scar production by producing collagen, elastin and glycosaminoglycans (long sugar chains that form part of the material between cells). They can also differentiate into myofibroblasts which contain actin (a muscle-like protein), so they can contract and close wounds.
In certain circumstances macrophages are unable to phagocytose, for example when there are foreign bodies or certain bacteria present. When this occurs, the macrophages fuse together to form giant cells that isolate the substance they cannot break down.
There are different types of giant cell. The type gives a clue to the cause, but none is specific to one disease:
Langhans Type - nuclei are arranged at the periphery, often in a horseshoe pattern. They occur in granulomatous inflammation (inflammation with granulomas, explained below), including tuberculosis (TB), but their appearance under the microscope does not establish TB on its own. Long-lasting triggers, for example infection with Mycobacterium tuberculosis (the bacterium that causes TB), can make macrophages fuse into giant cells. The cause must be established from the clinical context and further investigations.
Image - Histological Sample Showing a Langhans Type Giant Cell
Creative commons source by Ed Uthman [CC BY-SA 4.0 (https://creativecommons.org/licenses/by-sa/4.0)]
Foreign Body Type - nuclei are arranged randomly in the giant cell. They occur when there is a foreign body that macrophages can’t phagocytose.
Touton Type - nuclei form a ring around a central area of cytoplasm, with a foamy, lipid-rich rim outside the ring. They are seen in areas with high lipid content, such as fat necrosis (death of fatty tissue) and xanthomas (fatty yellow deposits in the skin or tendons). These giant cells have a foamy appearance due to the phagocytosis of lipid.
Effects of Chronic Inflammation
Fibrosis
This occurs when fibroblasts are stimulated to produce collagen. This process is initially helpful as it produces a fibrous scar to replace lost tissue and wall off the damaged or infected area.
However, fibrosis can become harmful when it replaces normal parenchymal tissue (the working cells) of an organ, leading to impaired function of the organ. An example is cirrhosis of the liver, which is advanced fibrosis (scarring that has distorted the liver's normal structure). Long-term damage to the liver causes fibrosis and over time this scarring distorts the structure of the liver and can shrink it. This increases resistance to portal blood flow and raises the pressure in the portal vein (portal hypertension). Portal hypertension contributes to ascites (a build-up of fluid in the abdomen).
Stimulation of Inappropriate Immune Responses
Inflammation is used by the immune system as a way of destroying its targets. However, the immune system can occasionally trigger inflammation at an inappropriate site. This occurs in autoimmune conditions such as rheumatoid arthritis. In rheumatoid arthritis the immune system attacks the cells that line the joints (the synovium), causing chronic inflammation. This leads to swelling and joint pain, and if untreated can cause joint destruction.
Granulomas
Sometimes chronic inflammation can be accompanied by the formation of granulomas.
A granuloma is formed when there are particles which are difficult to break down but need to be isolated and contained. These particles can include foreign bodies such as splinters, or bacteria such as Mycobacterium tuberculosis. Granulomas are a collection of epithelioid macrophages. These are macrophages which have been modified due to increased activity so look like epithelium. Giant cells can also be found in and around granulomas.
There are two general types of granuloma:
- Foreign Body Granulomas
- Develop around material that is not antigenic (does not trigger an immune response), e.g. surgical thread.
- Contains macrophages, foreign body giant cells, epithelioid macrophages and fibroblasts.
- Immune Type Granulomas
- Develop around insoluble particles (particles that do not dissolve) that carry antigens.
- Undergo central necrosis, especially in granulomas associated with tuberculosis.
- Present in infections such as tuberculosis, syphilis and leprosy (all bacterial infections) and fungal infections.
Granulomas can also be present in conditions where no specific antigen has been identified, such as sarcoidosis (a disease in which granulomas form, often in the lungs and lymph nodes) and Crohn's disease (a type of inflammatory bowel disease). They are also seen in granulomatosis with polyangiitis (GPA), a vasculitis (inflammation of blood vessels).
Edited by: Dr. Bethany Turner
Reviewed by: Dr. Josh Sturgeon and Dr. Marcus Judge
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