Lecture 21: Cellular Interactions and Trafficking - T cells

Question 1

Where do surviving SP thymocytes finish maturing? What do they express?

Answer 1

in the medulla

express S1P receptor and CD62L

Question 2

What do secondary lymphoid organs consist of?

Answer 2

lymph nodes, spleen, and mucosa-associated lymphoid tissues (MALTs)

Question 3

What do secondary lymphoid organs allow for?

Answer 3

recirculation of lymphocytes to survey the entire body which increases the odds of encountering antigen

Question 4

What can lymph nodes be segmented into?

Answer 4

B cell zones (follicles) and T cell zones (paracortex)

Question 5

What do lymph nodes house?

Answer 5

a variety of stromal cells and antigen presenting cells

Question 6

Where does lymph arrive?

Answer 6

via the afferent lymphatic and exits via the efferent lymphatic

Question 7

What is homing?

Answer 7

migration of naïve T cells and typically occurs in four stages involving a number of molecules

Question 8

What are the four stages of homing?

Answer 8

rolling, activation, adhesion and diapedesis

Question 9

How is rolling initiated?

Answer 9

with L-selectin (CD62L) on T cells and GlyCAM-1 on endothelial cells
MAdCAM-1 in mucosae

Question 10

How does activation occur?

Answer 10

chemokines such as CCL21 activate integrins such as LFA-1 which increases affinity for its ligand (ICAM-1/2)

Question 11

What occurs during adhesion?

Answer 11

strong interaction between LFA-1 and ligands and LFA-1 molecules are reorganised to be concentrated in areas of cell-cell contract

Question 12

What occurs during diapedesis?

Answer 12

cells extravasate by squeezing between endothelial cells

driven by chemotaxis

Question 13

What is the role of a high chemokine gradient of CCL19/21? Where are high levels of CCL19/21 found?

Answer 13

attracts lymphocytes with CCR7

in the paracortex

Question 14

What does CXCL13 in the follicles attract?

Answer 14

B cells (and some T cells) expressing CXCR5

Question 15

What is the role of dendritic cells?

Answer 15

important antigen presenting cells (APC) which can present antigen from different sources

Question 16

What are the two main types of conventional DCs?

Answer 16

lymphoid and migratory DCs

Question 17

What is the role of DCs in the periphery?

Answer 17

uptake antigen and migrate to LNs

interacts with T cells similar to lymphoid resident DCs

Question 18

How does adhesion occur between DC and T cells? What is the purpose of this adhesion?

Answer 18

weak interactions between LFA-1 and ICAM-1/2

allows for T cells to sample many MHC molecules

Question 19

What does effective priming of T cells require?

Answer 19

three different signals

Question 20

What is the first signal of T cell priming?

Answer 20

activation through TCR-MHC complex interaction which results in many transcriptional changes e.g. upregulation of CD69

Question 21

What is the second signal of T cell priming?

Answer 21

ligation of CD28 with co-stimulatory molecules B7.1 and B7.2 (CD80 and CD86)
modifies the IL-2 receptor through heterodimerization

Question 22

Where is the IL-2 receptor expressed and what is its affinity?

Answer 22

expressed on naive cells as a dimer

has moderate affinity to IL-2

Question 23

What does activation through CD28 upregulate in the IL-2 receptor?

Answer 23

the α chain (CD25) which increases affinity

Question 24

What does IL-2 receptor signalling cause?

Answer 24

causes T cells to enter the cell cycle and promote
proliferation
able to secrete IL-2 to sustain

Question 25

What do Treg cells constitutively express?

Answer 25

CD25 thus allowing it to act as a ‘sink’ for available IL-2

Question 26

What is the third signal of T cell priming?

Answer 26

secretion of cytokines that allow for differentiation of T cells for various effector functions
especially relevant for CD4 T cells

Question 27

What is DC licensing?

Answer 27

maturation of DCs by CD4 T cells to improve their ability to stimulate naïve CD8 T cells
important to control CD8 responses

Question 28

What key interaction occurs during DC licensing?

Answer 28

key interaction between CD40/CD40L

Question 29

What modulates exiting of cells via the efferent lymphatics?

Answer 29

S1P1 and CD69 negates S1P1r

CD69 is upregulated then downregulated following activation

Question 30

Which cells are primed first in HSV infection?

Answer 30

CD4 T cells are primed prior to CD8 T cells which helps regulate CD8 T cell responses and ensures specificity