Lecture 16

Question 1

What is meant by the term chronic inflammation?

Answer 1

Refers to inflammation of a prolonged duration in which active inflammation and tissue destruction occurs while attempts at repair occur simultaneously

Question 2

When does chronic inflammation occur?

Answer 2

1. AI fails
2. Repeat AI episodes
3. Due to unique characteristics of inciting stimulus

Question 3

Can chronic inflammation arise without a prior discernible AI phase?

Answer 3

yes

Question 4

What are the biological mechanisms under which AI occurs?

Answer 4

1. Persistence/Resistance (occurs with certain infections)
2. Isolation (microbial agents have developed mechanisms to hide from the pathogens
3. Unresponsiveness - inert yet an irritant (e.g. when certain foreign materials are indestructible- e.g grass seed)
4. Autoimmunity, hypersensitivity and leukocyte defects (genetic dysfunction of oxidative killing in leukocytes or in adaptive immune responses)
5. Unidentified mechanisms - unusual diseases e.g Alzheimer’s

Question 5

What are the classical cellular features that will always be observed

Answer 5

1. Cellular infiltrate (Macrophages = granulomatous inflammation, lymphocytes (+NK), plasma cells, multi nucleated giant cells, +/- eosinophils/mast cells, +/- neutrophils
2. Tissue destruction and replacement by inflammatory infiltrate
3. Attempts at healing by connective tissue (replacement of damaged tissue, proliferation, angiogenesis and organ architecture morphologically altered)

Question 6

Explain what happens in the process of sequestration:

Answer 6

Two concurrently occurring processes are occurring:

1) Cellular infiltration
2) Fibroplasia

If these processes fail the lesion eventually becomes completely walled off by collagen from the fibroblasts encapsulating the lesion and it’s agents functionally placing them outside the body.

Question 7

What do the macrophages come from?

Answer 7

They are derived from blood monocytes and they and migrate into areas of tissue injury.

Question 8

Differentiate between the M1 and the M2 macrophages:

Answer 8

M1 (Classical) = exposed to antigens, activated by endotoxin + TLR, then release ROS, NO, IL-1, IL-12 to promote inflammation and destruction of microbial pathogens.

M2 (alternative) = activated by IL-4, IL-13 to stimulate tissue repair

Question 9

What are the factors that are responsible for the conversion of monocytes to dendritic cells?

Answer 9

IL-4, GM-CSF

Question 10

What are the surface receptors that are expressed on dendritic cells?

Answer 10

TLR, lectins, +/- Fc, C3b

Question 11

What is the function of the dendritic cells?

Answer 11

They present the antigen to the T-lymphocytes resulting in the acquired/adaptive immune response

Question 12

What are the cytokines and growth factors that are produced by the dendritic cells?

Answer 12

Pro-inflammatory cytokines: IL-1, TNF-a, IL-12 (pro-inflammatory cytokines)
Anti-inflammatory: IL-10
Growth factors for fibrosis: FGF, TGF-B

Question 13

What is the name of the B lymphocytes that produce specific antibodies and appear morphologically different?

Answer 13

plasma cells

Question 14

Would lymphocytes be present in autoimmune and delayed type hypersensitivity responses?

Answer 14

yes

Question 15

Are lymphocytes present in granulomatous inflammation?

Answer 15

It is dependent on lymphocyte responses and bi-directional interaction between lymphocytes and macrophages

Question 16

What is the main type of cell that is found within connective tissue?

Answer 16

fibroblasts

Question 17

What is the role of fibroblasts?

Answer 17

1. They proliferate and synthesize ECM components providing structural integrity and tensile strength to wounds
2. They are a rich source of growth factors including keratinocyte GF and IGF-1

Question 18

What is chronic inflammation with macrophages classified as?

Answer 18

histiocytic

Question 19

What is chronic inflammation based on epithelioid macrophages and MNGC classified as?

Answer 19

granulomatous

Question 20

What is chronic inflammation based on lymphocytes and plasma cells called?

Answer 20

lymphoplasmacytic

Question 21

What is chronic inflammation based neutrophils and epithelioid macrophages called?

Answer 21

pyogranulomatous

Question 22

Briefly describe the gross pathology you would expect to observe as a consequence of chronic inflammation:

Answer 22

• Areas of swelling/thickening/nodularity
• Fibrosis - areas will appear pale and firm
• Cellular infiltration & proliferation - areas appear pale (cell type) and of variable texture (could be harder or softer)
• Concurrent tissue loss - the organ has an irregular surface +/- shrunken tissue loss

Question 23

What are the key features seen in a microbial abscess?

Answer 23

1. Persistent inciting agent (bacteria/fungi)
2. Acute inflammatory response (neutrophils) fails to kill the microorganism
3. Central lytic core of necrotic debris (purulent exudate) surrounded by a zone of macrophages/lymphocytes/plasma cells and encapsulated by fibrous tissue (walled off)

Question 24

What is the problem with chronic pulmonary abscesses?

Answer 24

They may also provide an environment suitable for micro-organism survival and low pH and O2 concentration means impaired neutrophil function

Question 25

What are some possible sequelae to abscess rupture?

Answer 25

External rupture: the cavity fills with granulation tissue and heals by second intention --> replacement by a fibrous connective tissue scar Internal rupture: Spreads along fascial planes --> widespread fasciitis/cellulitis --> ruptures into a blood vessel or airway --> bacteraemia and septicaemia

Question 26

What are the complications of osteomyelitis?

Answer 26

Sequestrum: necrotic bone acts as a foreign body Involucrum: subperiosteal new bone covers the sequestrum