Advanced Immunology Flashcards
Contains the following lectures: mechanisms of leukocyte migration, structure- and function of FC receptors, epigenetic regulation of immunity, regulation of transcription, Signal transduction by antigen receptors, cytokine receptors and PRR and Co-stimulation and co-inhibition of T cells
Where are almost all hematopoietic cells found?
In the blood (recirculation)
Location and migration of lymphocytes is important for… (4)
- Homing to organs or tissues
- Homing to compartments
- Cell cell interactions
- Exit from compartments/organs
What can be said about the kind of expression and what they attract if you talk about inflammatory chemokines?
- Induced expression
- Attract activated lymphocytes
What can be said about the kind of expression and what they attract if you talk about homeostatic chemokines?
- Constitutive expression in lymphoid organs
- Attract naive T/B/DCs
What are the mechanisms of attraction of leukocytes? (3)
- Chemotaxis
- Haptotaxis
- Chemo- or haptokinesis
Mechanisms of attraction of leukocytes: describe chemotaxis
Migration with a soluble gradient
Mechanisms of attraction of leukocytes: describe haptotaxis
Migration with a bound gradient
Mechanisms of attraction of leukocytes: describe chemo- or haptokinesis
Migration without a gradient
Which factors regulate cell migration? What do they attract?
- Chemokines
- Attract cells expressing the appropriate receptor
Which factors regulate adhesion of leukocytes? What are their ligands?
- Integrins
- Ligands: extracellular matrix proteins
What do integrins bind to?
Extracellular matrix and counter ligands
What are examples of other ligands for integrins?
VCAM-1, MadCAM-1, ICAM-1,2,3
Where do lymphocytes enter the lymph nodes?
At specialized blood vessels, called high endothelial venule (HEV)
What are high endothelial venules? What do they allow for?
- Specialized form of postcapillary blood vessel
- Allows for extravasation of cells
Where are HEVs found?
In T cell zones of LNs and PP
What can be said about the extravasation in resting lymph nodes?
Constitutive extravasation of naive T- and B lymphocytes
What are the steps of lymphocyte extravasation? (5)
- Rolling and tethering
- Sticking
- Crawling
- Transmigration
- Exit ramp/Accumulation in an HEV pocket
What induces rolling of lymphocytes in HEVs? What are they made by?
- Expression of specific sugars on the endothelial cells in the LN
- Made by enzymes
Which two enzymes are specific for endothelial cells? What does that imply?
- GlcNAc6ST2 and FUT7
- They make sugar structures that are unique for endothelial cells
Which molecule on leukocytes can specifically bind to the sugar structures on the endothelial cells?
L-selectin
What can be said about the binding between L-selectin and the sugar structures on the endothelial cells?
- Not a very high affinity binding
–> binding/release - Induces rolling along the endothelium
What causes sticking/full arrest of the leukocyte? Which two ways are there?
Chemokine-mediated activation of integrins:
- Inside-out signaling
- Outside-in signaling
What is integrin activation by inside-out signaling?
Chemokine receptor signaling changes integrin configuration:
- CCR7-CCL21 interaction causes a change in LFA-1 conformation on the T cell
What is integrin activation by outside-in signaling?
Integrins on leukocytes bind to integrin receptors on HEV –> high affinity:
- LFA-1 (after a conformational change) on T cells binds to ICAM-1 on HEVs
What cells synthesize S1P?
Endothelial cells and red blood cells. This makes S1P concentration high in bodily fluids and low in tissues, creating a gradient for T cells to follow.
What homeostatic chemokines attract B cells and T cells, respectively, and what cells produce them and where?
- CXCL13 is expressed by stromal cells in the B cell follicles.
- CCL21 is produced by stromal cells in the paracortex and promotes T cell and dendritic cell migration.
What is more common, chemotaxis or haptotaxis?
Haptotaxis