0.5 Chronic Inflammation

Question 1

What is chronic inflammation?

Answer 1

A delayed, prolonged response to injury or infection

Continuous destruction and repair of normal tissue is ALWAYS seen

Question 2

How can chronic inflammation be characterised?

Answer 2

Most common = presence of many macrophages + lymphocytes in affected tissues

Less common = presence of many neutrophils

Question 3

What are the 3 causes of chronic inflamamtion?

Answer 3

1. Persistent infections ie resistant pathogens or mycobacteria/viruses etc
2. Hypersensitivity diseases ie autoimmune or allergic
3. Prolonged exposure to exogenous/endogenous agents ie silica or cholesterol

Question 4

How do persistent infections lead to granulomatous inflammation?

Answer 4

1. Difficult to eradicate due to location/virulence fof agent eg periapical periodontitis
2. Unresolved acute inflammation evolves into chronic inflammation
3. Inflammatory response takes on a specific pattern called granulomatous inflammation

Question 5

What are the 3 patterns of chronic inflammation?

Answer 5

1. Granulomatous = macrophages predominate
2. Suppuration = chronic pus formation
3. Mixed / diffuse

Question 6

What are the key characteristics of granulomatous inflammation?

Answer 6

1. Characterised by accumulation of macrophages and T-cells into a ball (granuloma)
2. Sometimes with central necorsis (eg TB cases)
3. Cellular attempt to CONTAIN an offending agent that is difficult to eradicate

Question 7

Macrophages may undergo changes in granulomatous inflammation. What are these changes?

Answer 7

1. Differentiate = develop abundant cytoplasm and resemble epithelial cells (become epithelioid cells)
2. Fuse = form multinucleated GIANT CELL (langhans cells)

Question 8

What is the difference between granulation tissue and a granuloma?

Answer 8

Granulation tissue = newly formed tissue involved in healing damaged tissues via fibrosis, contains amcrophages, blood vessels, and fibroblasts

Granuloma = nodular inflammatory lesion predominantly containing macrophages, lymphocytes, and fibroblasts, which forms in response to persistent irritant

Question 9

What are the three types of chronic granulomatous inflammation?

Answer 9

1. Immune (eg TB)
2. Foreign body (eg older surgical sutures)
3. Unknown origin (eg sarcoidosis)

Question 10

What is the cell progression in the formation of a granuloma?

Answer 10

1. Monocyte (rolls, adheres, squeezes into ECM) and differntiate into macrophages
2. Some macrophages differentiate into epithelioid cell
3. Epitheloid cells combine into giant cells
4. Sphere forms around giant cell with lymphocytes enclosed by fibroblasts

Question 11

What are the two key roles of a granuloma?

Answer 11

1. To contain a microorganism / irritant in order to prevent its dissemination
2. To focus immune response against the initiating factor

Question 12

What impacts do TNF and anti-TNF have on inflammation?

Answer 12

TNF = important in macrophage activatino + priamry signal for granuloma formation

Anti-TNF = neutralises TNF cytokine, interfering with granuloma formation and/or compromises its stability or structure

Question 13

What are the 5 steps behind granuloma formation?

Answer 13

1. Certain bacteria, fungi, and foreign particles are unable to be killed/digested by phagocytes = incites agents
2. Chemokines regulate the recruitment of monocytes
3. Cytokines + monocytes = differentiation of macrophages into epitheliod cells
4. Cytokines + epithelioid cells = fusion into giant cells
5. Growth factors + giant cells = recruitment of fibroblasts and formation of fibrous tissue

Question 14

What are the two morphologies of giant cells?

Answer 14

1. Foreign body giant cell
2. Langhans giant cell

Question 15

What are the 3 characteristics of a foreign body giant cell?

Answer 15

1. Collection of fused macrophages
2. Nuclei overlap and are disorganised
3. Present in response to a large foreign body eg impants + amalgam tattoos

Question 16

What are the 3 characteristics of Langhans giant cells?

Answer 16

1. Formed by fusion of epithelioid cells
2. Nuclei arranged in a horseshoe shape pattern in the cell periphery
3. Found in nearly every form of granulomatous diseaseeg TB, sarcoidosis, syphilis

Question 17

What is tuberculosis?

Answer 17

Granulomas with necrosis

Caseous necrosis = TB always

Question 18

What are examples of hypersensitivity diseases, and how do they cause chronic inflammation?

Answer 18

1. Autoimmune diseases (rheumatoid arthritis, MS, rheumatic heart disease)

Auto-antigens evoke a perpetuating immune response that causes chronic inflamamtion + tissue damage

2. Allergic diseases

Common environmental substances trigger an excessive immune response causing chronic inflammation

Question 19

Prolonged exposure to exogenous and endogenous agents can cause chronic inflammation, depending on concentration and duration of exposure. What are examples of such exogenous and endogenous agents?

Answer 19

Exogenous agents = silica (inhaled for long periods = inflamamtory lung disease aka silicosis

Endogenous agents = cholesterol (excessive production and tissue deposition in arterial wall aka atherosclerosis)

Question 20

What are examples of non-conventional inflammatory diseases?

Answer 20

1. Alzheimer’s disease
2. Metabolic syndrome
3. Tyep II diabetes
4. Tumour development

Question 21

What are the two key mediators of chronic inflammation?

Answer 21

1. Macrophages
2. Lymphocytes

Question 22

Macrophages are the dominant cell type during chronic inflammation and persistent infections. What roles do they play?

Answer 22

1. Destroy invaders directly via phagocytosis
2. Secret cytokines and growth factors to activate T-lymphocytes

Question 23

What are the characteristics of classically activated macrophages (M1)?

Answer 23

Strongly pro-inflammatory = secretes cytokines that stimulate inflammation

Induced by microbial products (endotoxins) which engage TLRs and by IFN-y

Produce NO and ROS species to enhance killing of ingested organisms

Question 24

What are the characteristics of alternatively activated macrophages (M2)?

Answer 24

Induced by cytokines produced from T-cells etc

Not microbial, but aid tissue repair

Secrete growth factors to promote angiogenesis, activate fibroblasts, and stimulate fibrosis

Question 25

What are the key differences between classically activated macrophages (M1) and alternatively activated macrophages (M2)?

Answer 25

M1 = microbicidal actions + phagocytosis works to kill bacteria and fungi M2 = Anti-inflammatory effects + wound repair via fibrosis

Question 26

In most circumstances, macrophages disappear when the irritant and subequent inflammatory response is eliminated. What is the pathophysiology when macrophage accumulation persists?

Answer 26

Result of continuous recruitment and proliferation at site of inflammation Excessive tissue damage occurs via ROS species + increased fibrosis

Question 27

Lymphocytes are the predominant population in chronic inflammation caused from autoimmune and other hypersensitive diseases. What role do they play?

Answer 27

Microbes + other environmental antigens activate T and B lymphocytes, which amplify and propagate chronic inflammation Once activated, inflammation tends to be persistent and severe Granulomatous inflammation is dependent upon lymphocyte responses

Question 28

T-cells amplify reactions included by the early acute inflammatory response. What are some of the crucial subsets of T-cells and what do they do?

Answer 28

Th1 = (IFN-y) activates amcrophages by the classical pathway Th2 = recruit and activate eosinophils and are responsible for the alternative pathway of macrophage activation Th17 = (IL-17 + cytokines) induce secretion of chemokines responsible for recruiting neutrophils locally

Question 28

What are the key differences between Th1 + Th17 cells compared to Th2 cells?

Answer 28

Th1 + Th17 = defence against bacteria, viruses, and autoimmune diseases Th2 = defence against helminth parasites and allergic inflammation

Question 29

What is the role of eosinophils in chronic inflammation?

Answer 29

Abundant during parasitic infections and mediate IgE effects Contain major basic protein, toxic to parasites but also to host epithelial cells

Question 30

What is the role of mast cells in chronic inflammation?

Answer 30

Express IgE receptors and degranulate to release histamine prostaglandins Typically respond during allergic reactions Promote inflammation via the plethora of cytokines they produce

Question 31

What is a typical emigration pattern during inflammation?

Answer 31

1. PMNs are the predominate cell 2. Monocytes emigrate to become macrophages (new predominate cell) 3. As the amount of macrophages start to decrease, the amount of lymphocytes increase 4. Lymphocytes emigrate to contribute to immune response and fades out shortly after macrophages fully disappear from site

Question 32

What is osteomyelitis?

Answer 32

Inflammation or swelling that occurs in the bone

Question 33

What is the progression of osteomyelitis?

Answer 33

1. Bacteria enter bone canaliculi 2. Necrosis of osteocytes/bone 3. PMN + other antimicrobials unable to penetrate into osteocytic canaliculi or lacunae 4. Ensuing inflammation leads to bone destruction 5. Constant re-infection of tissue from infected necrotic bone 6. Hard to treat / recover from

Question 34

What is protective against osteomyelitis?

Answer 34

Bone resorption with formation of granulation tissue

Question 35

What are the key characteristics of mixed/difuse chronic inflammation patterns?

Answer 35

Mixed inflammatory infiltrate of PMN, macrophages, lyphocytes, plasma cells Usually specific immune responses Often has chronic inflammatory granulation tissue with fibrosis May undergo acute flare ups

Question 36

What is an example of mixed type chronic inflammation?

Answer 36

Rheumatoid arthritis - Neutrophils in synovial fluid - Lymphocytes and macrophages in pannus