Acute Inflammation - Cells Flashcards
Cells of Inflammation:
Granulocytes
Neutrophils
Eosinophils
Basophils
Cells of Inflammation:
Mononuclear Cells
Monocytes / Macrophages
Lymphocyters / Plasma Cells
Mast Cells
Neutrophils:
Morphology
- 10-15 micron diameter
- Segmented, multi-lobular nucleus
- Cytoplasmic Granules
- primary (azurophilic) granules
- Secondary (Specific) granules
Neutrophils:
Primary Granule Content
Myeloperoxidase
Lysozyme
Acid Hydrolases
Elastase
Cathepsin G
Neutrophils
Secondary Granule Content
Lysozyme
Collagenase
Gelatinase
Lactoferrin
Neutrphils:
Characteristics
- They are highly differentiated
- THey are no longer able to divide
- Cellular respiration can be mainly anaerobic
- contain abundant glycogen stores
- Can function in low oxygen environments
- Hypoxia-inducible Factor-1 (HIF-1a)
- They metabolize large amounts of oxygen in response to activation
Neutrophils:
Kinetics
- 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
- Approximately half of the intravascular neutrophils are marginated
- Once they emigrate the can live 1-4 days in tissues; depending on the situation
- Apoptosis occurs following withdrawal of growth factors and other stimuli
Neutrophils:
Major Inflammatory Functions:
Phagocytosis and Killing
-
Oxygen-independent Killing
- Phagolysosome formation allows granule content to act upon the inflammatory stimulus
-
Oxygen-dependent Pathways are prominent in neutrophils
- NADPH - assocaited oxygen radicals
- Myeloperoxidase dependent killing can occur, making neutrophils the most potent killers of all phagocytes
-
Nitric Oxide Pathways are also present
- Formulation of highly reactive peroxynitrite
Neutrophils:
Major Inflammatory Functions:
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
- Anitmicrobial peptides
- Neutrophil extracellular traps
- products of dead neutrophils that trap and possibly kill bacteria
Neutrophil Extracellular Traps
- Web-like matrix of DNA/proteins/ and neutrophil granule products secreted by neutrophils that trap and kill pathogens
- NETs contain concentrated myeloperoxidase, elastase, cathepsin G, amond 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
Eosinophils:
Morphology
- 15-20 micron diameter
- Segmented, bilobed nucleus
- Four types of cytoplasmic granules
- specific granules have characteristic crystalloid core
Eosinophil:
Granule Content
Major Basic Protein (MBP)
Eosinophil cationic protein
Arylsulfatase B
Histaminase
Phospholipase D
Peroxidase
Hydrolytic Enzymes
Collagenase
Eosinophil:
Characteristics
- Not as well understood as neutrophils
- Phagocytic, but much less so than neutrophils
- Prominent at sites of allergic reactions or parasitic infections
- Often occur in association wiht mast cells
- Respond to eosinophil chemotactic factor and histamine
Eosinophil:
Kinetics
Have a 30 minute half life in the blood
Have a 12 day half-life in tissue
Eosinophils:
Major Inflammatory Functions:
Secretion of lysosomal Enzymes
- Damage microbe membranes, but also the ECM
- Degradation of certain Pro-inflammatory products
- histaminase and histamine
Eosinophil:
Major Inflammatory Functions:
Secretion of other mediators
-
Cytokines
- Interleukins (1,6,8,12 among others)
- Transforming Growth Factor (TGF) a and B
-
Chemokines
- Eotaxin
-
Arachidonic Acid Metabolites
- LTC4, LTD4, LTE4
Basophil:
Morphology
- 8-12 micron Diameter
- Multilobed nucleus
- Cytoplasmic Gramules
Basophil:
Granule Content
Histamine
Proteoglycans
Chondrotin
Heparin
Proteases
Elastase
Tryptase
Basophil:
Characteristics:
- Not well understood
- Associated with sites of IgE-dependent allergic reactions or parasitic infections
- receptors for IgE and Eotaxin
- Poorly Phagocytic, and sluggishly motile
Basophil:
Kinetics
- Not well defined
- Probably similar to neutrophils
- Recruited into tissue from blood
- Have a life span of several days once in the tissue
- Recruited into tissue from blood
Basophil:
Major Inflammatory Functions:
Secretion of lysosomal Enzymes
- Effects include bronchoconstriction, vasodilation, and ECM degradation