Chronic Inflammation

Question 1

Name 3 examples of chronic inflammation

Answer 1

Periodontitis, Autoimmune diseases (e.g. rheumatoid arthritis), Orofacial Granulomatosis

Question 2

Name the 3 classes of chronic inflammation

Answer 2

1. Non-specific chronic inflammation
2. Specific (primary) chronic inflammation
3. Chronic granulomatous inflammation (a subset of specific chronic inflammation)

Question 3

What is the infiltrate dominated by in non-specific chronic inflammation?

Answer 3

Tissue macrophages, T cells and B cells

Question 4

What is non-specific chronic inflammation characterised by?

Answer 4

A dynamic balance between tissue destruction and repair

Question 5

Describe the ‘initiation’ stage in gingivitis/periodontitis

Answer 5

Microbes in dental plaque recognised by gingival epithelial cells via pattern recognition receptors (TLRs)

Question 6

Describe the ‘progression’ stage in gingivitis/periodontitis

Answer 6

Containment of microbes by innate immune cells and antimicrobial compounds (e.g. AMPs and secretory IgA)

Question 7

Describe the ‘amplification’ stage in gingivitis/periodontitis

Answer 7

Recruitment and activation of innate immune cells via chemokine/cytokine activity and vascular dilation

Question 8

What are the 2 types of specific chronic inflammation?

Answer 8

Granulomatous or non-granulomatous

Question 9

What is specific chronic inflammation characterised by?

Answer 9

Excessively activate macrophages

Question 10

What can specific chronic inflammation be induced by?

Answer 10

Non-immunological agents (foreign body reactions, inert noxious materials such as asbestos), or immunological agents (infective organisms that grow in cells, hypersensitivity reactions, autoimmune reactions, infection by fungi, protozoa or parasites)

Question 11

What is an autoimmune disease?

Answer 11

An example of specific chronic inflammation. An unwanted response to body’s own cells and tissues or commensal bacteria. Loss of tolerance to self antigens or commensal bacteria.

Question 12

What usually prevents autoimmunity?

Answer 12

Multiple mechanisms of tolerance (checkpoints)

Question 13

Describe the autoimmune disease ‘rheumatoid arthritis’

Answer 13

Autoreactive T cells against antigens found in joints in the body

Question 14

Describe the autoimmune disease ‘Crohn’s disease’

Answer 14

Autoreactive T cells against commensal bacteria found within the intestines

Question 15

Describe the autoimmune disease ‘Diabetes Type I’

Answer 15

Autoreactive T cells that target the islet cells within the pancreas, leading to the destruction of insulin producing beta-cells

Question 16

Describe the proposed link between rheumatoid arthritis and periodontitis

Answer 16

P. gingivalis infection in periodontitis produces PAD enzymes which convert arginine to citrulline. This leads to loss of tolerance. Citrulline is not a naturally occurring amino acid. Host will target citrulline containing proteins. This occurs in the joints in arthritis.

Question 17

How does chronic granulomatous inflammation differ from normal chronic inflammation?

Answer 17

The predominant cell types are macrophages known as epithelioid macrophages

Question 18

What are epithelioid macrophages?

Answer 18

Modified activated macrophages that can fuse to form giant multinucleate cells. They are more secretory than phagocytic. Found in chronic granulomatous inflammation.

Question 19

What are the causes of chronic granulomatous inflammation?

Answer 19

Immunological - delayed hypersensitivity type reaction or invading pathogens
Non-immunological - foreign body in tissues e.g. asbestos
Unknown causes

Question 20

What is the precursor to macrophages?

Answer 20

Monocytes. They circulate in the blood and migrate to the tissues where they differentiate into macrophages.

Question 21

What is the main aim of macrophages?

Answer 21

To phagocytose and present antigen

Question 22

Which macrophages are pro-inflammatory and which are anti-inflammatory?

Answer 22

Pro-inflammatory = M1
Anti-inflammatory = M2
Need a balance between M1 and M2

Question 23

What are the functions of M1 macrophages in tissue injury?

Answer 23

Release toxic oxygen metabolites, proteases, neutrophil chemotactic factors, coagulation factors, amino acid metabolites, nitric oxide

Question 24

What are the functions of M2 macrophages in tissue repair?

Answer 24

Process of fibrosis, growth factors (PGDF, FGF, TGF-beta), fibrogenic cytokines, angiogenesis factors, remodelling collagenases

Question 25

What are granulomas?

Answer 25

Clustering of macrophages and adaptive immune cells characterised by the formation of giant cells - epithelioid macrophages clustered together.

Question 26

What are the stages involved in the formation of a granuloma?

Answer 26

1. Macrophages present antigen to lymphocytes (T cells and B cells). 2. T cells produce IL-12, IL-2 and IFN-gamma. 3. This induced the formation of epithelioid macrophages. 4. Contribute further to giant cell formation (epithelioid macrophages aggregate) 5. Giant cell is formed - engulfs foreign material

Question 27

Name an example of chronic granulomatous inflammation.

Answer 27

Orofacial Granulomatosis (OFG)

Question 28

Describe the features of orofacial granulomatosis (OFG).

Answer 28

Granulomas present in oral cavity Swelling If patient has intestinal Crohn's - termed Oral Crohn's If not Crohn's - termed OFG

Question 29

Describe features of chronic periodontitis

Answer 29

``` Apical migration of the epithelial tissue and formation of a periodontal pocket Soft tissue (gingival tissue) destruction Hard tissue (alveolar bone) destruction Presence of inflammatory infiltrate consisting of defence cells ```

Question 30

What are the 7 stages of tissue destruction in periodontitis?

Answer 30

1) Initiation of immune response 2) Recruitment of immune cells 3) Immune cell activation 4) RANKL production 5) Activation of osteoclasts 6) Reduced function of osteoblasts 7) Activation of MMPs

Question 31

What are matrix metalloproteinases (MMPs)?

Answer 31

Enzymes produced by fibroblasts and other immune cells. MMPs remodel/degrade the extracellular matrix (ECM). This allows immune cells to move through tissue to site of infection.

Question 32

What is the extracellular matrix (ECM)?

Answer 32

A complex structure that supports cells. It provides a scaffold for immune cells moving through the tissue.

Question 33

What are the functions of MMPs?

Answer 33

``` Remodel the ECM Drive angiogenesis (formation of new blood vessels) ```

Question 34

What is osteoblastogeneis?

Answer 34

Bone formation

Question 35

What is osteoclastogenesis?

Answer 35

Bone resorption

Question 36

How often is the human skeleton completely remodelled?

Answer 36

Every 10 years

Question 37

What are the precursors for osteoclasts?

Answer 37

Macrophages

Question 38

What is RANKL?

Answer 38

Receptor Activator of Nuclear Factor Kappa-B Ligand. RANKL is produced by osteoblasts.

Question 39

What does RANKL do?

Answer 39

RANK-L, produced by osteoblasts, is a ligand that activates the RANK receptor on osteoclasts. This will lead to bone resorption.

Question 40

What is osteoprotogerin (OPG)?

Answer 40

Osteoprotogerin (OPG) is secreted by osteoblasts inhibits RANKL function, therefore controlling bone resorption.

Question 41

RANKL and OPG are secreted by...

Answer 41

Osteoblasts

Question 42

An increase in the RANKL/OPG ratio results in what?

Answer 42

An excessive immune response. Balance is tipped towards more bone resorption.