Cellular pathology: Inflammation and Healing

What are the causes of chronic inflammation?

• persistent infections

• foreign bodies

• autoimmune/immune-mediated conditions

• repeated mechanical/chemical injury

What type of immunity is chronic inflammation a part of?

adaptive immunity

What immune cells are involved in adaptive immunity?

B & T lymphocytes

What are activated lymphocytes?

mediators of adaptive immunity and are often present in chronic inflammation

What do CD4+ helper (Th) lymphocytes secrete?

cytokines

What does this image show?

lymphoplasmacytic inflammation

What does this image show?

suppurative chronic inflammation

What does this image show?

granulomatous and granuloma formation

What does this image show?

eosinophilic chronic inflammation

What does chronic inflammation start as?

diffuse mononuclear infiltration

1

macrophage

2

plasma cells

3

lymphocytes

What type of inflammation is common in chronic enteritis, thyroiditis & arthritis (autoimmune disorders)?

lymphoplasmacytic inflammation

In what conditions is lymphoplasmacytic inflammation common in?

• chronic enteritis

• thyroiditis 

• arthriti

What occurs during lymphoplasmacytic inflammation?

• widespread lymphocyte & plasma cell infiltration

• may form lymphoid follicles

What would you see looking at lymphoplasmacytic inflammation under the microscope?

• dense mononuclear infiltrate

• sometimes lymphoid follicle formation

What does this image show?

thyroiditis in African green monkey

1

thyroid follicles

2

lymphocytes & plasma cells

What is the arrow pointing to?

lymphoid follicle

What are the features of suppurative chronic inflammation?

• pus

• encapsulated abscesses

• persistent neutrophil recruitment & chronic mononuclear cells

Name examples of suppurative chronic inflammation

• suppurative bronchopneumonia

• purulent rhinitis 

What are encapsulated abscessed?

fibrous wall surrounding pus

What can you see under a microscope with suppurative chronic inflammation?

• central purulent core

• fibrous capsule

• peripheral mononuclear infiltrate

What does this image show?

liver abscesses in goat

What type of chronic inflammation does this image show?

suppurative chronic inflammation

black arrow

abscess

red arrow

capsule

blue arrow

pus

1

neutrophils

2

macrophages

3

fibroblast

What is granulomatous inflammation made of?

macrophages & giant cells

What are common causes of granulomatous inflammation?

• mycobacteria (bovine TB)

• fungi (cryptococcus, histoplasma)

• foreign material (suture granulomas)

What does this image show?

granuloma structure/formation

What is the structure of a granuloma?

• macrophages are dominant cells

• surrounded by lymphocytes, plasma cells & fibrous capsule

• central accumulation of degenerated cells/organisms/minerals

What food do granulomas look like?

soft cheese

How are granulomas formed?

1. macrophages engulf organisms

2. organism resists digestions, multiplies in macrophage

3. macrophage dies, engulfed by other macrophages

4. central caseous necrosis may mineralise

What does this image show?

macaque, spleen

1

degenerated core

2

macrophages

3

lymphocytes & plasma cells

4

fibroblasts

What does this image show?

horse, cutaneous mass

What does this image show?

pyogranuloma

1

fungi

2

neutrophils

3

macrophages

4

lymphocytes & plasma cells

5

fibroblasts

What is eosinophilic inflammation?

chronic inflammation with predominance of eosinophils

What are common causes of eosinophilic inflammation?

• parasitic infections

• hypersensitivity

What features do you see under the microscope for eosinophilic inflammation?

bright eosinophil granules often mixed with mast cells and lymphocytes

What does this image show?

beef cattle with coccidia

What is the yellow arrow pointing to?

inflammation

What is the red arrow pointing to?

coccidia parasite

1

lymphocytes & plasma cells

2

eosinophils

Define “chronic inflammation”

prolonged inflammation where tissue injury, attempted healing, and inflammation occur simultaneously

What are the pathological features of chronic inflammation?

• infiltration by mononuclear cells

• neutrophils & eosinophils

• tissue destruction by inflammatory cells

Define “healing”

the body’s process of replacing damaged or lost tissue with new living tissue

What are the 2 main reactions in healing?

• regeneration

• repair

What is “regeneration”?

undamaged cells proliferate to replace specialised tissue

What is “repair”?

damage replaced by granulation tissue → scar formation

What are the 3 phases of healing?

• inflammation

• proliferation

• remodelling

Does regeneration restore normal architecture and function to a tissue?

YES

Does repair restore normal architecture and function to a tissue?

NO

What does regeneration depend on?

cellular capacity to proliferate

Which cells proliferate and differentiate during regeneration?

tissue stem cells

What are labile cells?

cells that continuously proliferate at a certain rate

Name 4 examples of labile cells

• squamous epithelium (of skin, mouth, vagina & cervix)

• columnar epithelium ( of intestinal tract)

• transitional epithelium (of urinary tract)

• bone marrow cells

What are “stable cells”?

can proliferate but don’t normally do so

Name 3 examples of “stable cells”

• liver hepatocytes

• alveolar cells of lung

• epithelium of kidney tubules

What are “permanent cells”?

• neurons

• skeletal & cardiac muscle

What is scar tissue made of?

connective (fibrous) tissue

When is scar tissue formed?

when there’s loss or limited proliferation of parenchymal cells & if the supporting structures of the tissue (stroma) are severely damaged

What does scar form from?

maturation of granulation tissue

What is granulation tissue?

network of new blood vessels and collagen that fills a wound

What phase may precede inflammation?

haemostatic phase

Why does the haemostatic phase occur?

if vasculature is injured

What happens during the haemostatic phase?

• vasoconstriction

• aggregation of thrombocytes → platelet plug

• fibrin mesh formation → clot → scaffold for healing

What occurs during the inflammation stage?

initial stage where body sends cells to the injury site, causing symptoms like pain, swelling and redness as part of the natural healing response

What growth factors do M2 anti-inflammatory release?

• Transforming Growth Factor (TGFB)

• Endothelial Growth Factor (VEGF)

What do M2 macrophages do?

bridge inflammation & repair

What is proliferation?

1. new tissue (collagen & blood vessels) is laid down to replaced damaged area

2. tissue matrix is formed

3. reepithelization occurs at same time

What cells does proliferation involve?

• epithelial/parenchymal cells

• endothelial cells

• fibroblasts

What do epithelial/parenchymal cells do during proliferation?

restore function

What do endothelial cells do during proliferation?

proliferate to form new blood vessels

What do fibroblasts do during proliferation?

lay down collagen that form the stroma or scar

What is proliferation controlled by?

cell cycle

What do growth factors do?

stimulate proliferation

What are growth factors produced by?

• macrophages

• epithelial cells

• fibroblasts

During proliferation, what happens to epithelium adjacent to the wound?

undergoes activation and proliferation

During proliferation, what happens to the basement membrane?

provides scaffold to support cell migration into damaged area

angiogenesis

process of new blood vessel development from existing vessels

What happens to endothelial cells during angiogenesis?

endothelial cells grow from older intact blood vessels that branch out, form anastomoses with other vessels, and restore blood flow

What does granulation tissue contain?

• proliferating fibroblasts

• loose collagen

• new blood vessels

• scattered chronic inflammatory cells

What part of the wound does granulation tissue grow from?

base of wound

What size wound can granulation tissue fill?

ANY