Lecture 14

Question 1

Where does initiation and amplification of adaptive immune responses occur?

Answer 1

Secondary Lymphoid Organs

Question 2

How is the formation and organization of secondary lymphoid organs controlled?

Answer 2

By TNF family members

Question 3

Where do B and T cells enter the lymph node

Answer 3

high endothelial venules (HEVs)

Question 4

Where are HEVs found within the lymph node?

Answer 4

T-cell zones

Question 5

How is white pulp demarcated from red pulp in the spleen?

Answer 5

the marginal sinus

Question 6

Where are circulating B and T cells first delivered into in the spleen?

Answer 6

The marginal sinus

Question 7

What type of cells enrich the marginal sinus?

Answer 7

marginal zone B cells (they do not recirculate)

Question 8

Where do T cells and B cells go after they’ve entered the spleen through the marginal sinus?

Answer 8

T cells -> T cell zones
B cells -> B cell follicles

Question 9

Where are Fibroblast Reticular Cells Located and what is their function?

Answer 9

• stromal cells of the spleen
• produce chemokines to attract T cells from the marginal sinus

Question 10

Where are Follicular Dendritic Cells located and what is their function?

Answer 10

• follicular spleen cells
• produce CXCL13 chemokine to attract B cells from the marginal sinus

Question 11

How is antigen delivered to the spleen?

Answer 11

• delivered via arterioles
• antigen taken up by dendritic cells
• dendritic cells can take the antigen into the T-cell zone

Question 12

What is MALT?

Answer 12

mucosa-associated lymphoid tissue

Question 13

What are Peyer’s patches?

Answer 13

• lymph node-like structures
• beneath the gut epithelium
• type of MALT

Question 14

What are M cells?

Answer 14

• In Peyer’s Patches
• Channel antigens and pathogens directly from the gut lumen into the underlying lymphoid tissue

Question 15

What are the steps of naive T cell migration into the lymph node?

Answer 15

• circulating lymphocyte enters an HEV in the lymph node
• L-selectin (on lymphocyte) binds to GlyCAM-1 and CD34 (both on the endothelial cell) which allows a rolling interaction (weak interaction)
• LFA-1 (on lymphocyte) is activated by CCR7 (on lymphocyte) signaling in response to CCL21/CCL19 chemokines on the surface of endothelial cells
• activated LFA-1 binds tightly to ICAM-1
• Lymphocyte crosses the endothelium and enters the lymph node via diapedesis

Question 16

What are the molecules used by naive T cells to enter HEVs?

Answer 16

L-selectin, CD34, GlyCAM-1

Question 17

What molecules do ALL T cells use to enter HEVs?

Answer 17

LFA-1 and ICAM-1

Question 18

What molecules do naive, effector and memory T cells use to enter the endothelium of mucosal lymphoid tissue or marginal sinus of the spleen?

Answer 18

LPAM-1 and MAdCAM-1

Question 19

What happens to T cells that are not activated by antigen presented by DCs in the lymph node?

Answer 19

• they exit the lymph node via the cortical sinuses
• they recirculate through the circulation and SLOs to patrol for properly presented antigens

Question 20

When an antigen is detected in the lymph node, what happens to T cells?

Answer 20

Most antigen-specific T cells in the body will be trapped in the lymph fluid draining a site of infection. Increase in influx and decrease in efflux of lymphocytes into and out of the lymph node facilitated by local inflammation

Question 21

What mediates the egress of lymphocytes from lymphoid tissue?

Answer 21

S1P gradients

Question 22

Describe the S1P gradient relative to the blood, lymph and lymphoid tissue and how the gradient is created

Answer 22

• S1P is low in lymphoid tissue
• S1P is high in blood and lymph
• S1P lyase in T-cell zones breaks down S1P

Question 23

What is S1PR1 and where is it located?

Answer 23

* receptor for S1P * on the surface of naive T cells

Question 24

Describe how/when the S1P/S1PR1 interactions work to move lymphocytes

Answer 24

* high levels of S1P in the blood down-regulate the receptor, resulting in low levels if expression on naive T cells that have recently entered T cell zones * w/o antigen recognition, S1PR1 surface expression is increased on the naive T cell - cell senses the S1P gradient and egresses the lymphoid tissue * w antigen recognition, CD69 expression will increase which will result in the internalization of S1PR1 and retention of T cells in the T cell zones * CD69 expression eventually wanes, resulting in the antigen-activated T cells egression from the lymphoid tissue

Question 25

What is FTY720?

Answer 25

* an immunomodulatory molecule (can be used as medication) * works to retain T cells in the T cell zone * Can bind S1PR1 to modulate its expression (its binding results in internalization of S1PR1) w/o being degraded by S1P lyase in T-cell zones

Question 26

Where are DCs located and what is their effect on naive T cells when they present an antigen to them?

Answer 26

* ubiquitous throughout body * activation of naive T cells

Question 27

Where are macrophages located and what is their effect on T cells that they present an antigen to?

Answer 27

* in lymphoid tissue, connective tissue and body cavities * results in activation of macrophages by effector and memory T cells

Question 28

Where are B cells located and what is the effect they have on T cells when they present antigens

Answer 28

* in lymphoid tissue and peripheral blood * results in delivery of help to B cell by TFH cells

Question 29

What is priming?

Answer 29

the first contact that antigen-specific naive T cells have with an antigen

Question 30

what are the two major classes of DCs?

Answer 30

1. conventional 2. plasmacytoid

Question 31

What is the difference between conventional and plasmacytoid T cells?

Answer 31

Conventional: * primarily concerned with activation of naive T cells * most abundant in non-lymphoid tissues but they also populate SLO Plasmacytoid: * sentinels of viral infection * secrete large amounts of type I IFNs

Question 32

How are transient adhesive interactions between T cells and DCs stabilized?

Answer 32

* T cells initially bind APCs thru low affinity LFA-1-ICAM-1 interactions * subsequent binding of T cell receptors signals LFA-1 to undergo conformational change * Conformational change in LFA-1 increases affinity and avidity that result in prolonged cell-cell contact

Question 33

What are the three kinds of signals involved in the activation of naive T cells?

Answer 33

1. TCR recognition of antigen peptide - MHC on surface of activated conventional DCs 2. co-recognition of costimulatory molecules (CD28-B7) 3. cytokines delivered to activated naive T cell by APC

Question 34

What is the role of IL-2 in T-cell activation?

Answer 34

* drives clonal expansion * activated T cells can either secrete or respond to IL-2

Question 35

What happens after 4-5 days of rapid clonal expansion of T cells?

Answer 35

T cells differentiate into effector cells that no longer need co-stimulation to perform their effector functions (cytotoxicity or cytokine secretion

Question 36

Describe the expression levels of: * L-selectin * CCR7 * LFA-1 * S1PR1 * VLA-4 from naive to effector T cells

Answer 36

* L-selectin: increased in naive -> none in effector * CCR7: increased in naive -> none in effector * LFA-1: moderate in naive -> increased in effector * S1PR1: moderate in naive -> none in effector * VLA-4: none in naive -> moderate in effector

Question 37

What are TH1 effector T cells specialized for?

Answer 37

* microbes that resist macrophage killing * extracellular bacteria

Question 38

What are TH2 effector CD4 cells specialized for?

Answer 38

helminth parasites

Question 39

What are TH17 effector CD4 cells specialized for?

Answer 39

* extracellular bacteria

Question 40

what are Treg effector CD4 cells specialized for?

Answer 40

self and microbiome derived

Question 41

what are the proteins in granules of cytotoxic T cells?

Answer 41

* perforin * granzymes * granulysin

Question 42

What molecules are involved in the extrinsic pathway for apoptosis?

Answer 42

* Fas / FasL * FADD * caspase 8 * caspase 3 * I-CAD / CAD

Question 43

What molecules are involved in the intrinisic pathway of apoptosis?

Answer 43

* cytochrome c * Apaf-1 * pro-caspase 9 * pro-caspase 3 * ICAD / CAD