Inflammation: Cells Flashcards
What Granulocytes are involved in Inflammation?
- Neutrophils
- Eosinophils
- Basophils
What Mononuclear cells are involved in Inflammation?
- Monocytes/macrophages
- Lymphocytes/plasma cells
- Mast Cells
What is the morphology of Neutrophils?
- 10-15 micron diameter
- Segmented, multilobed nucleus
- Cytoplasmic granules (lysosomes)
- Primary (Azurophilic) granules
- Secondary (Specific) granules
What is the primary granule content of neutrophils?
- Myeloperoxidase
- Lysozyme
- Acid hydrolases
- Elastase
- Cathepsin G
Varies by species: Birds and reptiles have lower enzyme concentrations compared to mammals
What is the secondary granule content of Neutrophils?
- Lysozyme
- Collagenase
- Gelatinase
- Lactoferrin
Varies by species: Birds and reptiles have lower enzyme concentrations compared to mammals
What are the characteristics of Neutrophils?
- Highly differentiated
- No longer abl to divide
- Cellular respiration may be mainly anaerobic
- Contain abundant glycogen stores
- Can function in low oxygen environments
- Hypoxia-inducible factor 1-alpha
- They metabolize large amounts of oxygen in response to activation
What does Hypoxia-inducible factor 1-alpha do?
- Induces transcription of genes that enhance phagocytosis and secretion, and inhibit apoptosis
What are the kinetics of Neutrophils?
- Produced in the bone marrow, where they remain for 1.5 days after maturation in a storage pool
- Pool is 5x the circulating concentration
- Once they enter the blood they circulate for 5-12 hours
- ~½ of intravascular neutrophils are marginated
- Once they emigrate they can live 1-4 days in tissues, depending on the situation
- Apoptosis following withdrawal of growth factors and other stimuli
What are Neutrophil’s function in Phagocytosis and Killing?
- Oxygen-independent killing
- Oxygen-dependent pathways*
- Nitric oxide pathways
What are the Oxygen-Independent killing pathways of Neutrophils?
- Phagolysosome formation allows granule content to act upon the inflammatory stimulus
What is the Oxygen-dependent killing pathway in Neutrophils?
- Oxygen-dependent pathways are prominent in neutrophil
- NADPH - associated oxygen radicals
- Myeloperozidase killing can occur making neutrophils the most potent killers of all phagocytes
What are the Nitric oxide killing pathways with Neutrophils?
- Nitric oxide pathways are also present
- Formation of highly reactive peroxynitrite
How are Neutrophils involved with the secretion of inflammatory products?
- Lysosomal enzymes and oxygen metabolites can be released into the extracellular space
- Can kill extracellular pathogens, but also destroy ECM
- Cytokines (IL-8)
- Products of arachidonic acid metabolism
- LTB4, PGE2, TXA2, PAF
- Antimicrobial peptides (defensins)
- Neutrophil extracellular traps (NETs)
- Products of dead neutrophils that trap and possibly kill bacteria
What are Neutrophil extracellular traps?
- A web-like matrix of DNA/proteins/and neutrophil granule to products secreted by neutrophils that trap and kill pathogens
- NETs contain concentrated myeloperoxidase, elastase, cathepsin G, among others
- NETs may also be involved in autoimmunity and thrombosis
- Intracellular products within NETs may stimulate an immune response
- Platelets regulate and interact with intravascular NETs
What is the morphology of Eosinophils?
- 15-20 micron diameter
- Segmented, bilobed nucleus
- 4 types of cytoplasmic granules
- Specific granules have characteristic crystalloid core
What is the Granule (lysosome) content of Eosinophils?
- Major Basic Protein (MBP)
- Eosinophil cationic protein
- Arylsulfatase B
- Histaminase
- Phospholipase D
- Peroxidase
- Hydrolytic enzymes
- Collagenase
What are the Characteristics of Eosinophils
- Not as well understood as neutrophils
- Phagocytic, but much less so than neutrophils
- Prominent at sites of allergic reactions of parasitic infections
- Often occur in association with mast cells
- Respond to eosinophil chemotactic factor and histamine
What are the kinetics of Eosinophils?
- Have a 30 minute half-life in blood
- Have a 12 day half-life in tissue
What is the function of Eosinophils in Inflammation?
- Secretion of lysosomal enxymes
- Secretion of other mediators
What happens with eosinophil secreted lysosomal enzymes?
- Damage microbe membranes, and the ECM
- Degradation of certain pro-inflammatory products
- histaminase and histamine
What other mediators do Eosinophils secrete?
- Cytokines
- Interleukins (1, 6 ,8, 12 among others)
- Transforming Growth Factors (TGF) alpha and beta
- Chemokines (Eotaxin)
- Arachidonic acid metabolites
- LTC4, LTD4, LTE4
What is the morphology of Basophils?
- 8-12 micron diameter
- Multilobed nucleus
- Cytoplasmic (metachromatic granules)
What are the characteristics of Basophils?
- Not well understood
- Associated with site of IgE-dependent allergic reactions or parasitic infections
- Have receptors for IgE and exotaxin
What are the kinetics of Basophils?
- Not well defined
- Probably similar to neutrophils
- Recruited into tissue from blood
- Have lifespan of several days once in tissue
What are Basophils’ function in Inflammation?
- Secretion of lysosomal enzymes
- Secretion of other mediators
What effects do Basophil secreted lysosomal enzymes have?
- Effects include:
- bronchoconstriction
- Vasodilation
- ECM degradation
What other inflammation mediators do Basophils secrete?
- Cytokines:
- IL-4, IL-13
- IL-4 is critical in the IgE response to allergens
- IL-4, IL-13
- Arachidonic acid metabolites
- LTD4
- Chemokines
What is the morphology of Mast Cells?
- 10-15 micron diameter
- Oval to round nucleus
- Metachromatic cytoplasmic granules
- Granule content includes:
- histamine
- Serotonin
- Proteoglycans
- Chondrotin/heparin
- Proteases
- Elastase
- Tryptase
- Granule content includes: