Pathology 7: Cellular Events in Acute Inflammation Flashcards
What is leukocyte Extravasation?
What is leukocyte Extravasation margination, rolling, and adhesion?
- During normal blood flow endothelium does not “catch” the cells so it does more of a rolling
What is leukocyte Extravasation transmigration?
When leukocytes “crawls” through endothelium
- Mainly venules
- Also called diapedesis
What is leukocyte Extravasation migration?
Leukocyte in interstitial tissue toward a chemotactic stimulus
How does blood stasis effect leukocyte Extravasation?
Help leukocytes stack up at periphery
How does rolling effect leukocyte Extravasation?
- Leukocytes adhere transiently to endothelium
- Roll until cytokines stimulate a firm attachment
What cells use blood stasis and rolling?
Neutrophils
monocytes
eosinophils
basophils
myphocytes
What are the three families of adhesions molecules?
- Selectins
- Integrins
- Immunoglobulin family receptors
What are adhesion molecules with low affinity rolling mediated by?
Mediated by selectins expressed on surface of endothelium and leukocytes
What are adhesion molecules with high affinity binding mediated by?
Mediated by Integrins on leukocytes bind to to immunoglobulin family receptors on endothelial cells
What causes deficiencies in leukocyte adhesion?
Genetics- heritable deficiencies in type and amount of adhesion molecules can inhibit leukocyte transmigration and acute inflammation
What happens in transmigration mechanisms? What makes it possible?
- Leukocyte inserts a pseudopod into the junction between endothelial cells and squeezes through
- Made possible adhesion molecules on leukocytes and endothelial cells
What is chemotaxis and what are the two categories of products?
Movement of leukocytes in tissue along a chemical gradient
- Exogenous
- Endogenous
What are the chemotaxis exogenous products?
Bacteria
What are the chemotaxis endogenous products?
- Complement system components
(Leukotrienes, cytokines)
How does a cell move by chemotaxis?
Cell moves by extending a filopodia that pulls the back of the cell forward toward site of inflammation
What is phagocytosis?
- Recognition and attachment
- Engulfment
- Killing and degradation of ingested material
**Macrophages, dendritic cells, neutrophils
What are the leukocytes receptors and responses?
- G-protein coupled receptors
-TLRs
—- TLR-4 : LPS - Cytokine receptors
- Phagocytic receptor
What is engulfment?
- The pseudopods flow around particle to form a phagosome
- Phagosome fuses with lysosome in cell creating the phagolysosomes
What is killing and degradation?
- Reactive oxygen species (ROS)
- Lysosomal enzymes
What does genetic heritable deficiencies in terms of disease lead to?
- Results in poor inflammatory response to pathogens and dead tissues
- Causes recurrent infections
What is the difference between monocyte and macrophages
Monocyte = blood
Macrophage = tissue
What are the mechanisms of ROS?
Reactive oxygen species
- Produced within the lysosome
- Respiratory burst - rapid oxidative reaction
- Primary mode of microbial killing
What does release of leukocyte products during killing cause?
Collateral damage
What is collateral damage caused by?
- 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)
What type of phagocyte creates to most collateral damage?
Neutrophils
What are NETs?
Neutrophil extracellular traps
- Mechanism of killing microbes
How does a NET work?
Suicide bombers- in response to infectious pathogens and inflammatory mediators
- Extracellular fibrillar network
What is Extracellular fibrillar network composed of?
- Nuclear chromatin (sticky part)
- Antimicrobial peptides and enzymes (destructive part)
What is a leukocyte adhesion deficiencies? (LAD)
- Inheritied defects in leukocytes adhesions
- CLAD
- BLAD
What is chediak-higashi syndrome?
Inherited defects in phagolysosome fusion
What three features of genetic defects in leukocyte function lead to recurrent infections?
- chediak-higashi syndrome
- leukocyte adhesion deficiencies
- Inherited defects in microbial activity
What causes acquired defects in leukocyte function?
Cytopenia
- Bone marrow supression –> decreased production of leukocytes
- Leukemia, radiation, chemotherapy
What mechanisms turn off inflammation?
- Mediators run out - have a short half life
- Stop signals - actively shut off inflammation
What are the mechanisms of stop signals?
- Switch from pro-inflammatory arachidonic acid metabolites to inhibitory lipoxins
- Release of anti-inflammatory cytokines: TGF-B and IL-10
