Chronic Inflammation

Chronic inflammation is an ongoing inflammatory response occurring from an unresolved insult. It results as a continuation of acute inflammation, or arises de-novo (with the acute inflammatory response bypassed).


Macrophages

Macrophages are the major phagocytic cell in chronic inflammation, acting to engulf and destroy foreign material and/or pathogens. They are derived from monocytes.

In addition to phagocytosis, macrophages act as antigen presenting cells (APCs) – where there is antigen presentation between innate and adaptive immune cells. This process allows for a more coordinated and targeted response from the immune system.

A distinctive property of macrophages in chronic inflammation is their ability to fuse and form multinucleated giant cells. They are produced in response to certain stimuli, such as a foreign body (foreign-body giant cell), mycobacterium tuberculosis (Langhans giant cell), or fat necrosis (Touton giant cell).

Macrophages are also capable of secreting growth factors (to aid cell repair and synthesise complement components) and cytokines (to help coordinate the immune response).

Fig 1 - Multinucleated giant cells, which are formed by the fusion of macrophages.

Fig 1 – Multinucleated giant cells, which are formed by the fusion of macrophages.


Lymphocytes

In chronic inflammation, lymphocytes work in conjunction with APCs to process antigens, thereby coordinating a suitable inflammatory response. There are two main types – B lymphocytes and T lymphocytes.

B Lymphocytes

When appropriately stimulated, B lymphocytes differentiate into plasma cells. These cells produce antibodies, which can bind to cell antigens and consequently are able to:

  • Neutralise microbes and toxins (binding to and blocking the harmful effects of the antigen), to prevent infective and toxic effects of the antigen.
  • Promote natural killer cells to destroy targeted and tagged pathogens (antibody dependant cellular cytotoxicity (ADCC)).
  • Facilitate easier phagocytosis by the innate immune cells (termed opsonisation).

T Lymphocytes

T helper lymphocytes (CD4+ cells) act to co-ordinate further targeted inflammatory responses, from both innate and adaptive immune cells. T killer lymphocytes (CD8+ cells) act to co-ordinate the targeted destruction of infected cells.

Fig 2 - The roles of B lymphocytes (left) and T lymphocytes (right) in chronic inflammation.

Fig 2 – The roles of B lymphocytes (left) and T lymphocytes (right) in chronic inflammation.

Granulomas

In chronic inflammation, macrophages and lymphocytes can combine to form a granuloma – a means by which the immune system can ‘wall off’ an agent particularly resistant to destruction.

A granuloma contains a collection of elongated macrophages, termed epithelioid cells, surrounding a core of lymphocytes and giant cells attempting to break down the particles.

Fig 3 - A granuloma from a patient with sarcoidosis, showing a central core of lymphocytes surrounding by macrophages

Fig 3 – A granuloma from a patient with sarcoidosis, showing a central core of lymphocytes surrounding by macrophages

They are observed in several disease states, such as:

  • Tuberculosis
  • Sarcoidosis
  • Crohn’s disease
  • Rheumatoid arthritis
  • Granulomatosis with polyangiitis (GPA)

As granulomatous inflammation progresses, fibroblasts begin to lay down scar tissue, whilst the central core can become necrotic due to the release of enzymes (particularly seen in tuberculosis).

Further Reading

Chemokines as Therapeutic Targets to Improve Healing Efficiency of Chronic Wounds
Satish L et al., Advanced Wound Care

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