Adhesion and chemtaxis Flashcards
What is movement of leukocytes controlled by?
Chemical stimuli and tissue expression of adhesion molecules
Where do adhesion molecules present?
On leukocytes and on the endothelial
Define tethering and rolling
Slows down the movement of cells and enables them to be positioned where the site of inflammation and infection takes place
What is tethering and rolling guided by?
Specific homing receptors and ligands known as selectins
Where are L-type selectins expressed?
BY LEUKOCYTES
Where are P-type selectins expressed?
BY (PLATELETS) ENDOTHELIUM
Where are E-selectin expressed?
BY ENDOTHELIUM expression induced by cytokines or LPS (bacterial product)
What are selectins?
Lectin-like adhesion molecules
Carbohydrate receptors
What is the role of the matrix metalloproteinases?
Involved in degrading the tight junctions of the endothelial cells
Define integrins
Heterodimeric proteins expressed on the surface of leukocytes
Describe the 2 types of integrins
common beta2 chain and 3 forms of alpha chain, alphaL, alphaM, alphaX
What does leukocyte activation induce?
Conformational change - increases affinity - makes them stickier
Clustering of integrins - help stick better together
What does rolling activate?
Activates integrins - they receive signals from the CK on the endothelial surfaces helps to direct the cells strongly adhere and flatten
Name the 2 intracellular adhesion molecules (ICAM) and where they are expressed
ICAM-2 - basally expressed on endothelium - there all the time
ICAM-1 - induced by cytokines IL-1, TNF
Where is alpha4/beta1 (VLA-4) expressed?
ON eosinophils, monocytes and T cells
Binds vascular cell adhesion molecule
What is transmigration?
Involves CAMS and chemoattractants
Leukocytes pass from the endothelium from the blood into the tissue
Define chemoattractant and what are they are known as
Chemical that causes the attraction of cells
Chemotaxins
Describe the matrix metallo proteinases in transmigration
Zinc binding metallo proteinases - break down proteins
Degrade extracellular matrix
Promote migration through cellular tight junctions
Modulate expression of adhesion molecules and chemokines
What types of cells do they attract?
varies
non-selective - LTB4, C3a, C5a, formyl peptides
selective - chemokines
Describe chemotactic cytokines
Structually defined group of chemotaxins
Produced in response to IL-1, TNF, bacteria
G-protein coupled receptors
Originally named according to their function
systemic names according to chemokine structures - Ligand (L) and receptor (R)
Define chemokine receptors
Different chemokines bind to different receptors
Bind to chemokines
20 different types
7 membrane structure that couples to G protein for signal transduction
4 different families - CXC, CC, CX3C, and XC
