Chronic inflammation

Question 1

What is a chronic inflammation?

Answer 1

• Inflammation of a prolonged period
• Tissue destruction due to the huge number of inflammation factors
• Sometimes follows acute inflammation other times insidiously

Question 2

What causes chronic inflammation?

Answer 2

1) Persistent infection by certain microorganisms (Lox toxicity evoking immune response named “delayed-type hypersensitivity”, like in TB)

2) Prolonged exposure to toxic agents (like carbon inhalation)

3) Autoimmunity (which can cause chronic tissue damage and inflammation like rheumatoid arthritis and lupus erythematosus)

Question 3

What are the morphologic features of chronic inflammation?

Answer 3

• In contrast to acute inflammation, which is manifested by vascular changes, edema,
  and predominantly neutrophilic infiltration, chronic inflammation is characterized by:

1) Infiltration with mononuclear cells (macrophages, lymphocytes, and plasma cells)
2) Tissue destruction (due to persistent offending agents or inflammatory cells)
3) Healing (connective tissue replacement of damaged tissue, fibrosis, and angiogenesis)

Question 4

What is the role of macrophages in chronic inflammation?

Answer 4

• Component of the mononuclear phagocyte system
• The dominant cellular player
• Myeloid descendant
• Named according to the tissue they are in (for ex, in the CNS ”microglia”, in the liver “Kupffer cells” in the lungs “alveolar macrophages”, in the bones “osteomas”), or from monocytes in the blood

Question 5

Describe the mechanism by which macrophages are activated.

Answer 5

1) Circulating lymphocytes adhere to the endothelium

2) Macrophages emigrate to tissue

3) Macrophages are activated by:
1) Classically activated macrophages (M1) via Microbes & IFN-y:
- Releases ROS, NO, & lysosomal enzymes which have microbicidal actions (phagocytosis and killing of many bacteria) & IL-1, IL-12, IL-23, & chemokines (which induces inflammation)
2) alternatively activated macrophages (M2) via IL-13 & IL-4:
- Releases Growth factors, TGF-b (causes tissue repair and fibrosis), & IL-10, and TGF-b (Anti-inflammatory effects)

4) Activated macrophages secrete a wide variety of biologically active products, which results in tissue injury and fibrosis characteristic of inflammation

Question 6

What are the other cells (other than macrophages) involved in chronic inflammation?

Answer 6

1) Lymphocytes
- Usually, they are small in size, very dark nuclei, with scanty cytoplasm

Question 7

How do macrophages activate T-lymphocytes?

Answer 7

1) Release of cytokines
- IL-12
- IL-6
- IL-23

2) Prenting antigens to T-cells

Question 8

How does activated macrophages recruit leukocyte to the inflamed site?

Answer 8

By the release of:
- TNF
- IL-1

Question 8

How does T-lymphocytes (Th1, Th17), recruits leukocyte?

Answer 8

By their release of:
1) IL-17
2) TNF

Question 8

How do T-cells activate macrophages?

Answer 8

By the secretion of INF-y

Question 8

What is the function of eosinophils in chronic inflammation?

Answer 8

• Mediated by IgE
• Associated with allergies and parasitic infections
• Contains granules made of major basic proteins, toxic to parasites and can cause lysis of epithelial cells (contributes to tissue damage in immune reactions)

Question 9

What is the important chemokine for the recruitment of eosinophils?

Answer 9

eotaxin

Question 9

What is indicated by the high amount of neutrophils?

Answer 9

Acute inflammation (bacterial infection)

Question 10

What is meant by Granulomatous inflammation?

Answer 10

• Distinctive pattern of chronic inflammation
• Aggregation of activated macrophages with scattered lymphocytes

Question 10

What is the difference between the morphologic patterns in acute and chronic inflammation?

Answer 10

In chronic inflammation, you will see chronic inflammatory cells (Macrophages, Lymphocytes, monocytes, etc), destruction of parenchyma, and replacement by connective tissue, on the other hand in acute inflammation neutrophils fill the alveolar spaces and BV are congested

Question 10

Describe the role of mast cells in chronic inflammation

Answer 10

• Widely distributed in connective tissue
• Expresses Fc receptors that bind to IgE leading to mast cell degranulation (mainly histamine release)
• Producing cytokines that contribute to fibrosis

Question 10

Elevated lymphocytes for a short period of 2-3 days can indicate..?

Answer 10

If not chronic then viral infection

Question 10

What causes the formation of granuloma?

Answer 10

1) Persistent T-cell responses to certain microbes (like mycobacterium tuberculosis)
2) Immune-mediated inflammatory diseases (Crohn’s disease)
3) Sarcoidosis
4) Inert foreign bodies, forming foreign body granulomas (as the body cannot engulf it)

Question 11

What are some examples of diseases that cause Granulomatous inflammation?

Answer 11

Tuberculosis

Question 11

What are epitheloid cells?

Answer 11

The activated macrophages of the granulomatous inflammation might develop abundant cytoplasm resembling epithelial cells, which can fuse forming giant cells in the periphery or in the center of granulomas which are either arranged either peripherally (Langhans-type giant cell “similar to a horseshoe”) or haphazardly (foreign body-type giant cell)

Question 12

What are the types of granulomas?

Answer 12

1) Immune granulomas, due to a variety of agents that are capable of inducing a persistent T cell-mediated immune response, producing granulomas when the inciting agent cannot be readily eliminated, such as a persistent microbe or a self-antigen, macrophages activate T cells to produce cytokines, such as IL-2, activating other T cells, perpetuating the response, and IFN-γ, which activates the macrophages

• Most of the time the middle area of necrosis seen is a caseous necrosis

2) Foreign body granulomas
- Can be seen in drug abusers
- Due to inert foreign bodies, when they are large enough to be phagocytosed, like talc, sutures, and other fibers
- Forms epitheloid cells and giant cells surrounding the foreign body
- Foreign body is usually found in the middle of the granuloma

Question 13

What are the major differences between chronic and acute inflammation?

Answer 13

1) In acute there is Redness, Warmth, Pain, and swelling while in chronic there are little signs and fibrosis

2) In acute the major cell is neutrophils, while in chronic lymphocytes, macrophages, etc

3) In acute there is vascular damage, while in chronic there is neo-vascularization (new blood vessels, due to physiological/ pathological process)

4) In acute there is little or no fibrosis, while in chronic there is prominent fibrosis and less exudate