Leukocyte Structure and Function Flashcards
Which cell lineage do Leukocytes originate from?
Both myeloid and lymphoid progenitors
Activation of Leukocyte
A change in morphology and behavior of a leukocyte resulting from an extracellular signal
CD
Cluster of Differentiation
Cell surface markers
Over 350
Enable identification of functional subsets
Myeloid Cell Line
First line of defense against pathogens and tissue damage
Include inflammatory cells that regulate inflammatory response
Necessary for development of adaptive immune system
Most abundant leukocyte?
Least abundant leukocyte?
Most = neutrophil 55-70% Least = monocyte 3-8%
Neutrophils
PMNs
Characteristic dark and light granules Multi-lobed nucleus phagocytotic and activator of bactericidal mechanisms highly chemotactic CHIEF CELL of ACUTE INFLAMMATION
PRR
Pattern Recognizing Receptors
Found on neutrophils and macrophages
Recognize PAMPs and DAMPs
How do neutrophils kill pathogen?
Intracellular killing:
phagocytosis followed by oxidative burst
phagosome fuses with lysosome
phagolysosome creates oxidative burst that creates reactive oxygen species.
Primary Granules of Neutrophils
Dark staining
Antimicrobial proteins and compounds
Fuse with endosomes and empty contents
Kill ingested bacteria
Secondary Granules of Neutrophils
Pale
Fuse with endosomes and trigger oxidative burst
Release contents EXTRACELLULARLY
Tertiary Granule of Neutrophils
Contain gelatinase (MMP-9) that breaks down ECM for migrating neutrophil
Difference between 1, 2, and 3rd granules of neutrophils?
Primary granule fuses with the endosome while 2 and 3rd granules are excreted
Oxidative Respiratory Burst
Increased O2 consumption
Production of O2 (-)
Production of H2O2 and other bactericidal ROS
Granules Specific to Primary and Secondary Granules
Primary: Myeloidperoxidase (MPO) and Sulfated PG
Secondary: Lactoferria, Collagenase, B12 binding protien
Major Enzyme of Oxidative Burst
NADPH oxidase
made up of 5 subunits (2 bound to membrane)
Found in secondary granule
Remains cytosolic until it is activated.
Converts O2 to O2(-)
Then superoxide dismutase converts ROS to H2O2
Myeloperoxidase
MPO
Only found in primary granule
converts H2O2 to hypochloric acid
Catalase
Breaks down H2O2 to non-harmful H2O, O2
Chronic Granulomatous Disease
Mutation in NADPH oxidase
In ability to form O2 (-) from O2
Inhibits oxidative burst
Eosinophils
Kiling of antibody-coated parasites
Primarily tissue resident cells
Basophils
(similar to mast cells)
Release granules containing histamine (both mast and basophils)
Circulating cell (mast cells are resident)
Circulate as mature cells
Source of blood histamine
Monocytes
Enter tissue to become resident macrophages
Patrol circulation for sites of injury/ infection
Both inflammatory (CD14+) and repairative (CD16+)
Biphasic response to infection
Macrophage
Derived from circulating monocyte
APC cell with phagocytic and bactericidal mechanism
Scavengers, Secretory Cells, Regulators and APCs
Difference between macrophages and neutrophils
Mac are long lived, self replicating and adaptive with modest metabolic burst
Neuts hour life span, have single function, accumulate quickly then die, strong metabolic burst
Where does leukocyte Trafficking occur?
Capillary beds
Signs of Inflammation
Redness, swelling, heat, pain
Control of Inflammation
Cell adhesion molecules (CAMs) and chemokines expressed by ENDOTHELIAL cells and Leukocytes regulate migration into and out of tissues
CAM family
Selectin binds to Mucin-Like CAMs (MLC)
Integrins bind to Ig-superfamily CAMs
Leukocyte / Neutrophil Trafficking
Tethering Rolling Activation Adhesion Diapedesis Transversing Basal lamina Migration through ECM
Rolling
selectin mediated adhesion weakly adheres leukocyte to endothelial surface causing rolling like motion
Activation
Chemokines secreted by endothelium signal through G Protein Coupled receptors
Integrins are activated (Inside-Out activation)
Binding causes conformational change of integrins
Diapedesis
Leukocytes extedns across endothelial junctions and some through the cell.
Vascular integrity is maintained via zipper like mechanism
