Chapter 3: Chronic inflammation

Question 1

Can inflammation, tissue injury and (attempt at) tissue repair coexist in chronic inflammation?

Answer 1

Yes

Question 2

What are three main causes of chronic inflammation?

Answer 2

Persistent infection by microorganisms that are difficult to eradicate or an unresolved (persistent) acute inflammation that evolves into a chronic inflammation.
Hypersensitivity diseases.
Prolonged exposure to potentially toxic agents (endo- or exogenous).

Question 3

What are characteristics of chronic inflammation?

Answer 3

Infiltration with mononuclear cells (macrophages, lymphocytes, plasma cells).
Tissue destruction
Attempts at healing by connective tissue replacement of damaged tissue, accomplished by angiogenesis and fibrosis.

Question 4

What is the most dominant type of cells in chronic inflammation?

Answer 4

Macrophages

Question 5

From what cells are macrophages derived from?

Answer 5

Hematopoietic stem cells in the bone marrow (and from progenitors in
the embryonic yolk sac and fetal liver during early development).

Question 6

What are the macrophages called that circulate in the blood?

Answer 6

Monocytes

Question 7

What is meant by the mononuclear phagocyt system (or previously and wrongly named reticuloendothelial system)?

Answer 7

Macrophages are scattered in most connective tissues found in specific locations in organs such as the liver, spleen, lymph nodes, central nervous system and lungs.

Question 8

Why do macrophages

often become the dominant cell population in inflammatory reactions?

Answer 8

Because they have a much longer lifespan of months/years than e.g. monocytes (half-life of 1 day).

Question 9

What kind of signals/stimuli induce classical macrophage activation?

Answer 9

Microbial products such as endotoxins and by T cell-derived signals such als IFN-y.

Question 10

What happens when macrophages are classically activated (M1)?

Answer 10

The M1-macrophages produce ROS and NO and upregulate lysosomal enzymes.

Question 11

For what are M1/classically activated macrophages important?

Answer 11

For host defense against microbes and inflammatory reactions.

Question 12

What kind of signals/stimuli induce alternative macrophage activation?

Answer 12

It is induced by cytokines (other than IFN-y) such as IL-4 and IL-13 produced by T lymphocytes and other cells.

Question 13

What happens when macrophages are alternatively activated (M2)?

Answer 13

It induces tissue repair. M2 macrophages secrete growth factors for angiogenesis, activate fibroblasts and stimulate collagen synthesis.

Question 14

Which cells are dominant in chronich inflammation seen in autoimmune and other hypersensitivity diseases?

Answer 14

Lymphocytes

Question 15

What is the function of CD4+ T lymphocytes?

Answer 15

They promote inflammation and influence the nature of the inflammatory reaction.

Question 16

Which three CD4+ T lymphocytes are there?

Answer 16

Th1, Th2 and Th17.

Question 17

What cytokine is produced by Th1 and what is its function?

Answer 17

Th1 cells, produce cytokine IFN-y. It activates macrophages by the classical pathway.

Question 18

What cytokine is produced by Th2 and what is its function?

Answer 18

Th2 cells secrete IL-4, -5 and -13. They recruit and activate eosinophils and activate macrophages by the alternative pathway.

Question 19

What cytokine is produced by Th17 and what is its function?

Answer 19

Th17 cells secrete IL-17 and other cytokines. They induce the secretion of chemokines responsible for recruiting neutrophils into the reaction.

Question 20

How is chronic inflammation maintained by lymphocytes and macrophages?

Answer 20

They constantly interact with each other. A macrophage displays antigens to T cells, expresses costimulators that activates T cells and produces cytokines that stimulate the T cell respons. An activated T cell will in turn produce cytokines that recruit and activate macrophages. This promotes more antigen presentation and cytokine secretion.

Question 21

What other cells are often present in a chronic inflammation?

Answer 21

B lymphocytes and plasma cells.

Question 22

What are tertiary lymphoid organs?

Answer 22

This is an accumulation of lymphocytes, antigen-presenting cells and plasma cells clustered together to form lymphoid structures resembling the follicles found in lymph nodes.

Question 23

In what kind of diseases are tertiary lymphoid organs typically found (TRI)?

Answer 23

They are often seen in the synovium of patients with longstanding rheumatoid arthritis, in the thyroid in Hashimoto
thyroiditis, and in the gastric mucosa in the setting of Helicobacter pylori infection. (TRI)

Question 24

In what sort of immune reactions are eosinophils in abundance?

Answer 24

In immune reaction mediated by IgE and in parasitic infections.

Question 25

How are eosinophils recruited/activated?

Answer 25

Similar to neutrophils, it is driven by adhesion molecules and by specific chemokines derived from endothelial cells and leukocytes.

Question 26

Why do eosinophils contribute to both tissue damage as to controlling (parasitic) infections?

Answer 26

Because they contain a protein that is toxic to parasites but also injures host epithelial cells.

Question 27

Where do mast cells originate from and where do they reside?

Answer 27

They originate from the bone marrow and reside in connective tissues

Question 28

What kind of receptor do mast cells express and what can it bind?

Answer 28

They express the FceRI receptor which binds to the Fc portion of IgE antibodies.

Question 29

Mast cells are present in chronic inflammatory reactions. In what kind of reactions do they have a role besides this?

Answer 29

In allergic reactions.

Question 30

What is the characterisation of a granulomatous inflammation?

Answer 30

It is a form of chronic inflammation characterised by collections of activated macrophages, often with T lymphocytes and sometimes associated with central necrosis.

Question 31

What happens to active macrophages in granulomatous inflammation?

Answer 31

Macrophages develop abundant cytoplasm and begin to reseble epithelial cells (epithelioid cells). Other macrophages may fuse, forming multinucleate giant cells.

Question 32

True or false: Granuloma formation is a cellular attempt

to contain an offending agent that is difficult to eradicate.

Answer 32

True

Question 33

What kind of granuloma is formed when there’s an inciting agent that cannot be readily eliminated? What happens during this respons?

Answer 33

An immune granuloma is formed, here macrophages activate T cells to produce cytokines, such as IL-2, which activates other T cells, perpetuating the
response, and IFN-γ, which activates the macrophages. The goal is a super strong immune reaction.

Question 34

When are foreign body granulomas formed?

Answer 34

Foreign body granulomas form around materials that are large enough to exclude phagocytosis as an option.

Question 35

In what kind of situations do granulomas form (TRI)?

Answer 35

In persistent T cell responses where T-cell derived cytokines are responsible for chronic macrophage activation and granuloma formation. They can also form in immune-mediated inflammatory disease like Crohn disease. And also in sarcoidosis (TRI)

Question 36

Which disease is the prototype of a granulomatous disease caused by infection?

Answer 36

Tuberculose.

Question 37

A serous inflammation can be a result of a skin blister. What is a histological characteristic?

Answer 37

The epidermis that seperates from the dermis by a focal collection of serous effusion.

Question 38

Epitheloid cells can be seen under a microscope because of what?

Answer 38

They’re bigger and have indistinct cell boundaries. They’re also surrounded by lymphocytes.

Question 39

What cells are typical in a granuloma?

Answer 39

Epitheloid cells and Langhans giant cells.

Question 40

What is a characteristic of a granuloma associated with certain infectious organisms (like tuberculose)?

Answer 40

They often contain a central zone of necrosis.

Question 41

What is the term for the type of necrosis that occurs during formation of a granuloma associated with certain infectious organisms (like tuberculose)?

Answer 41

Caseous necrosis