Pathology 7: Cellular Events in Acute Inflammation

Question 1

What is leukocyte Extravasation?

Question 2

What is leukocyte Extravasation margination, rolling, and adhesion?

Answer 2

• During normal blood flow endothelium does not “catch” the cells so it does more of a rolling

Question 3

What is leukocyte Extravasation transmigration?

Answer 3

When leukocytes “crawls” through endothelium
- Mainly venules
- Also called diapedesis

Question 4

What is leukocyte Extravasation migration?

Answer 4

Leukocyte in interstitial tissue toward a chemotactic stimulus

Question 5

How does blood stasis effect leukocyte Extravasation?

Answer 5

Help leukocytes stack up at periphery

Question 6

How does rolling effect leukocyte Extravasation?

Answer 6

• Leukocytes adhere transiently to endothelium
• Roll until cytokines stimulate a firm attachment

Question 7

What cells use blood stasis and rolling?

Answer 7

Neutrophils
monocytes
eosinophils
basophils
myphocytes

Question 8

What are the three families of adhesions molecules?

Answer 8

• Selectins
• Integrins
• Immunoglobulin family receptors

Question 9

What are adhesion molecules with low affinity rolling mediated by?

Answer 9

Mediated by selectins expressed on surface of endothelium and leukocytes

Question 10

What are adhesion molecules with high affinity binding mediated by?

Answer 10

Mediated by Integrins on leukocytes bind to to immunoglobulin family receptors on endothelial cells

Question 11

What causes deficiencies in leukocyte adhesion?

Answer 11

Genetics- heritable deficiencies in type and amount of adhesion molecules can inhibit leukocyte transmigration and acute inflammation

Question 12

What happens in transmigration mechanisms? What makes it possible?

Answer 12

• Leukocyte inserts a pseudopod into the junction between endothelial cells and squeezes through
• Made possible adhesion molecules on leukocytes and endothelial cells

Question 13

What is chemotaxis and what are the two categories of products?

Answer 13

Movement of leukocytes in tissue along a chemical gradient

• Exogenous
• Endogenous

Question 14

What are the chemotaxis exogenous products?

Answer 14

Bacteria

Question 15

What are the chemotaxis endogenous products?

Answer 15

• Complement system components
  (Leukotrienes, cytokines)

Question 16

How does a cell move by chemotaxis?

Answer 16

Cell moves by extending a filopodia that pulls the back of the cell forward toward site of inflammation

Question 17

What is phagocytosis?

Answer 17

• Recognition and attachment
• Engulfment
• Killing and degradation of ingested material

**Macrophages, dendritic cells, neutrophils

Question 18

What are the leukocytes receptors and responses?

Answer 18

• G-protein coupled receptors
  -TLRs
  —- TLR-4 : LPS
• Cytokine receptors
• Phagocytic receptor

Question 19

What is engulfment?

Answer 19

• The pseudopods flow around particle to form a phagosome
• Phagosome fuses with lysosome in cell creating the phagolysosomes

Question 20

What is killing and degradation?

Answer 20

• Reactive oxygen species (ROS)
• Lysosomal enzymes

Question 21

What does genetic heritable deficiencies in terms of disease lead to?

Answer 21

• Results in poor inflammatory response to pathogens and dead tissues
• Causes recurrent infections

Question 22

What is the difference between monocyte and macrophages

Answer 22

Monocyte = blood
Macrophage = tissue

Question 23

What are the mechanisms of ROS?

Answer 23

Reactive oxygen species
- Produced within the lysosome
- Respiratory burst - rapid oxidative reaction
- Primary mode of microbial killing

Question 24

What does release of leukocyte products during killing cause?

Answer 24

Collateral damage

Question 25

What is collateral damage caused by?

Answer 25

• Release of lysosomal enzymes and ROS into the extracellular space
• Cytotoxic release- crystals can puncture the cell during phagocytosis and lead to leakage of enzyme and other leukocyte products (urates)

Question 26

What type of phagocyte creates to most collateral damage?

Answer 26

Neutrophils

Question 27

What are NETs?

Answer 27

Neutrophil extracellular traps
- Mechanism of killing microbes

Question 28

How does a NET work?

Answer 28

Suicide bombers- in response to infectious pathogens and inflammatory mediators

• Extracellular fibrillar network

Question 29

What is Extracellular fibrillar network composed of?

Answer 29

• Nuclear chromatin (sticky part)
• Antimicrobial peptides and enzymes (destructive part)

Question 30

What is a leukocyte adhesion deficiencies? (LAD)

Answer 30

• Inheritied defects in leukocytes adhesions
• CLAD
• BLAD

Question 31

What is chediak-higashi syndrome?

Answer 31

Inherited defects in phagolysosome fusion

Question 32

What three features of genetic defects in leukocyte function lead to recurrent infections?

Answer 32

• chediak-higashi syndrome
• leukocyte adhesion deficiencies
• Inherited defects in microbial activity

Question 33

What causes acquired defects in leukocyte function?

Answer 33

Cytopenia
- Bone marrow supression –> decreased production of leukocytes
- Leukemia, radiation, chemotherapy

Question 34

What mechanisms turn off inflammation?

Answer 34

• Mediators run out - have a short half life
• Stop signals - actively shut off inflammation

Question 35

What are the mechanisms of stop signals?

Answer 35

• Switch from pro-inflammatory arachidonic acid metabolites to inhibitory lipoxins
• Release of anti-inflammatory cytokines: TGF-B and IL-10