Entry of naive T cells and APCs into peripheral lymphoid organs

Question 1

Dendritic cells pick up antigen at sites of infection and travel to local lymphoid organs. What three things do they do in the lymphoid organs?

Answer 1

1. Mature
2. Present antigen to T cells
3. Activate T cells

Question 2

Naive T cells are continuously recirculating through the peripheral lymphoid tissues, surveying APCs for foreign antigens. What two factors facilitate this cellular traffic?

Answer 2

1. Chemotactic cytokines (chemokines)

2. Adhesion molecules

Question 3

Naive T cells circulate through PLOs sampling peptite:MHC complexes. Name three PLOs

Answer 3

1. Spleen
2. Lymph nodes
3. MALT (mucosa-associated lymphoid tissue

Question 4

What occurs to a naive T cell when it encounters a DC with MHC presented antigen that matches it’s TCR?

Answer 4

The T cell ceases migration, proliferates for several days undergoing clonal expansion, giving rise to a clone of effector T cells with identical antigen specificity.

Question 5

What cells are generated by clonal expansion? Where do they go?

Answer 5

Effector T cells, which exit the PLO via efferent lymphatics re-enter the circulation and can migrate to sites of infection.

Question 6

What PLO has no lymphatics? How to T cells enter and exit?

Answer 6

The spleen. Effector T cells or unstimulated naive T cells enter and exit direct to the blood stream.

Question 7

What governs T cell non-specific binding to high endothelial venules?

Answer 7

Cell adhesion molecules

Question 8

What are the four main classes of cell adhesion molecules?

Answer 8

1. Selectins
2. Integrins
3. Members of the immunoglobulin superfamily
4. Some mucin-like molecules

Question 9

List the four stages of lymphocyte entry into lymph nodes

Answer 9

1. Rolling along the endothelial surface
2. Activation of integrins
3. Firm adhesion
4. Transmigration or diapedesis across the endothelial layer to paracortical areas (the T cell zones)

Question 10

What coordinates the four stages of lymphocytes into lymph nodes?

Answer 10

Interplay between adhesion molecules and chemokines

Question 11

Most cell adhesion molecules have broad roles in immune responses, and are not just involved in lymphocyte migration. List four.

Answer 11

1. Interactions between naive T cells and APCs
2. Interactions between effector T cells and their targets
3. Interactions of other types of leukocytes with endothelium (e.g. monocytes and neutrophils migrating to infected tissue)
4. T and B cell interactions

Question 12

Which CAM is important for specifically guiding leukocytes to particular tissues? What is this phenomenon known as?

Answer 12

Selectins, leukocyte homing

Question 13

List three selectins, their CD ID, and location of expression.

Answer 13

1. L selectin, CD62L, expressed on leukocytes
2. P selectin, CD62P, expressed on vascular endothelium
3. E selectin CD62E, expressed on vascular endothelium

Question 14

Which selectin guides T cell exit from the blood into peripheral lymphoid tissues by initiating light attachment to the wall of the HEC, resulting in T cells rolling along the endothelial surface?

Answer 14

L selectin

Question 15

Which selectins are expressed on the vascular entothelium at sites of infection and recruit effector cells into the infected tissue?

Answer 15

P and E selectin

Question 16

………… are cell surface molecules with a common core structure, distinguished from eah other by the presence of different ……-like domains in their extracellular portion. The ……. domains bind to particular sugar groups, and each ……… binds to a cell surface carbohydrate.

Answer 16

Selectins, lectins, lectin, selectin

Question 17

L-selectin binds to the carbohydrate moiety sulfated ……..-…….x of …………-like molecules called vascular ……………… .

Answer 17

sialyl-lewisx
mucin-like
addressins

Question 18

Where are vascular addressins expressed?

Answer 18

On the surface of vascular endothelial cells

Question 19

Give two examples of vascular addressins that are expressed in HEV in lymph nodes

Answer 19

CD34, GlyCAM-1

Question 20

What addressin is expressed in mucosal endothelium? what does it do?

Answer 20

MAdCAM-1, guides lymphocyte entry into mucosal lymphoid tissue eg peyers patches.

Question 21

What is the interaction of L selectin and the vascular addressins responsible for?

Answer 21

The specific homing of naive T cells to lymphoid organs.

Question 22

Is L selectin interaction with vascular addressins adequate to facilitate lymphocytes crossing the endothelial barrier? What is required for this?

Answer 22

No, this requires an interaction between integrins and chemokines.