Lecture 21: Cellular Interactions and Trafficking - T cells Flashcards
Where do surviving SP thymocytes finish maturing? What do they express?
in the medulla
express S1P receptor and CD62L
What do secondary lymphoid organs consist of?
lymph nodes, spleen, and mucosa-associated lymphoid tissues (MALTs)
What do secondary lymphoid organs allow for?
recirculation of lymphocytes to survey the entire body which increases the odds of encountering antigen
What can lymph nodes be segmented into?
B cell zones (follicles) and T cell zones (paracortex)
What do lymph nodes house?
a variety of stromal cells and antigen presenting cells
Where does lymph arrive?
via the afferent lymphatic and exits via the efferent lymphatic
What is homing?
migration of naïve T cells and typically occurs in four stages involving a number of molecules
What are the four stages of homing?
rolling, activation, adhesion and diapedesis
How is rolling initiated?
with L-selectin (CD62L) on T cells and GlyCAM-1 on endothelial cells
MAdCAM-1 in mucosae
How does activation occur?
chemokines such as CCL21 activate integrins such as LFA-1 which increases affinity for its ligand (ICAM-1/2)
What occurs during adhesion?
strong interaction between LFA-1 and ligands and LFA-1 molecules are reorganised to be concentrated in areas of cell-cell contract
What occurs during diapedesis?
cells extravasate by squeezing between endothelial cells
driven by chemotaxis
What is the role of a high chemokine gradient of CCL19/21? Where are high levels of CCL19/21 found?
attracts lymphocytes with CCR7
in the paracortex
What does CXCL13 in the follicles attract?
B cells (and some T cells) expressing CXCR5
What is the role of dendritic cells?
important antigen presenting cells (APC) which can present antigen from different sources
What are the two main types of conventional DCs?
lymphoid and migratory DCs
What is the role of DCs in the periphery?
uptake antigen and migrate to LNs
interacts with T cells similar to lymphoid resident DCs
How does adhesion occur between DC and T cells? What is the purpose of this adhesion?
weak interactions between LFA-1 and ICAM-1/2
allows for T cells to sample many MHC molecules
What does effective priming of T cells require?
three different signals
What is the first signal of T cell priming?
activation through TCR-MHC complex interaction which results in many transcriptional changes e.g. upregulation of CD69
What is the second signal of T cell priming?
ligation of CD28 with co-stimulatory molecules B7.1 and B7.2 (CD80 and CD86)
modifies the IL-2 receptor through heterodimerization
Where is the IL-2 receptor expressed and what is its affinity?
expressed on naive cells as a dimer
has moderate affinity to IL-2
What does activation through CD28 upregulate in the IL-2 receptor?
the α chain (CD25) which increases affinity
What does IL-2 receptor signalling cause?
causes T cells to enter the cell cycle and promote
proliferation
able to secrete IL-2 to sustain
What do Treg cells constitutively express?
CD25 thus allowing it to act as a ‘sink’ for available IL-2
What is the third signal of T cell priming?
secretion of cytokines that allow for differentiation of T cells for various effector functions
especially relevant for CD4 T cells
What is DC licensing?
maturation of DCs by CD4 T cells to improve their ability to stimulate naïve CD8 T cells
important to control CD8 responses
What key interaction occurs during DC licensing?
key interaction between CD40/CD40L
What modulates exiting of cells via the efferent lymphatics?
S1P1 and CD69 negates S1P1r
CD69 is upregulated then downregulated following activation
Which cells are primed first in HSV infection?
CD4 T cells are primed prior to CD8 T cells which helps regulate CD8 T cell responses and ensures specificity
