Lecture 11 - Linking Innate & Adaptive Immunity (Traveling to Lymphoid Tissues and Visualizing Antigen Presentation)

Question 1

What cell type travels from the site of infection to lymphoid tissues?

Answer 1

Dendritic Cell

Question 2

Through what do dendritic cells travel?

Answer 2

Lymphatic Vessels

Question 3

What do dendritic cells express that targets them to lymphoid tissue?

Answer 3

Receptors

Question 4

True or False?:

When activating T-cells, APCs deliver activation (through costimulation), survival (through cytokines), and differentiation (through pMHC:TCR) signals.

Answer 4

False

When activating T-cells, APCs deliver activation (through pMHC:TCR), survival (through costimulation), and differentiation (through cytokines) signals.

Question 5

Where do immature dendritic cells reside?

Answer 5

Peripheral Tissues

Question 6

True or False?:

Dendritic cells migrate via lymphatic vessels to regional lymph nodes.

Answer 6

True

Question 7

True or False?:

Mature dendritic cells activate naive T-cells in peripheral tissues.

Answer 7

False

Mature dendritic cells activate naive T-cells in lymphoid organs such as lymph nodes.

Question 8

What are the three main lymphoid tissues?

Answer 8

Lymph Nodes, Spleen, Peyer’s Patch

Question 9

Through what do DCs enter lymph nodes?

Answer 9

Afferent Lymphatics

Question 10

Through what do T- and B-cells enter lymph nodes?

Answer 10

High Endothelial Venules (HEVs)

Question 11

What are DCs “loaded” with when they enter the lymph node?

Answer 11

Antigen

Question 12

True or False?:

Mature dendritic cells enter the lymph node from infected tissues and can transfer some antigens to resident dendritic cells.

Answer 12

True

Question 13

True or False?:

Only lymph node resident DCs can stimulate naive T-cells.

Answer 13

False

Both mature DCs from infected tissues and resident DCs can stimulate naive T-cells.

Question 14

What happens when DCs encounter PAMPs?

Answer 14

TLR signaling induces expression of a receptor that targets DCs to lymphatics and lymphoid tissues and increases the processing of antigen.

Question 15

Upon intial activation, how do DCs continue to mature? What does this result in?

Answer 15

DCs continue to mature through the induced expression of costimulatory molecules and the increased expression of MHC molecules. This results in an activated DC capable of priming naive T-cells.

Question 16

What is the difference between an unactivated DC and an activated DC in a lymphatic vessel?

Answer 16

The unactivated DC can phagocytose while the activate DC can’t.

Question 17

What are the two types of DCs?

Answer 17

Conventional and Plasmacytoid

Question 18

What is the difference between a conventional and a plasmacytoid DC?

Answer 18

Conventional DCs travel to lymphoid tissues to activate T-cells and act as classical APCs while plasmacytoid DCs stay at the site of infection where they are capable of producing large amounts of type I IFN and secrete cytokines to amplify local responses.

Question 19

True or False?:

Immune cells move into and out of tissues during innate and adaptive immune responses.

Answer 19

True

Question 20

What do lymphocytes do while moving into tissues from the blood?

Answer 20

While moving into tissues from the blood, lymphocytes constantly scan for Ag to which they can respond.

Question 21

What do T-cells do if they don’t encounter Ag upon in the lymph node?

Answer 21

They leave via efferent lymphatics.

Question 22

What do T-cells do when they encounter Ag presented by DCs in the lymph node?

Answer 22

T-cells activated by Ag presented by DCs start to proliferate and lose the ability to exit from the lymph node. The activated T-cells differentitate into effector T-cells and then exit the lymph node via efferent lymphatics.

Question 23

Dr. Krawczyk’s lab is studying DC activation. Pcgf6 is known to be a transcriptional repressor. DCs were stimulated with LPS (a PAMP) or remained unstimulated (u/s). They then measured Pcgf6 mRNA levels and IL12b mRNA levels (a proinflammatory cytokine released upon PRR signaling). Which of the following conclusions is best supported by this data?

• LPS stimulation downregulates nuclear translocation of Pcgf6.
• Upregulation of IL12b expression following LPS stimulation may result in lower transcription of Pcgf6.
• IL12b mRNA expression is higher with LPS stimulation.
• Downregulation of Pcgf6 expression following LPS stimulation may result in transcription of IL12b.

Answer 23

Downregulation of Pcgf6 expression following LPS stimulation may result in transcription of IL12b.

Question 24

What are the four stages of T-cell entry into the lymph node? What is each stage mediated by?

Answer 24

Rolling (Selectins), Activation (Chemokines), Adhesion (Integrins), Diapedesis (Chemokines)

Question 25

True or False?:

Selectins on T-cells can bind to receptors to target them to lymphoid tissues. Different tissues (like HEV and mucosal endothelium) express different receptors.

Answer 25

True

Question 26

What do integrins on T-cells bind to, giving rise to migration?

Answer 26

Adhesion Molecules

Question 27

True or False?:

The same adhesion molecules are found on all surfaces.

Answer 27

False

Different adhesion molecules are found on HEV (lymph node), mucosal epithelium (Peyer’s patch), and activated endothelium (return of activated effector T-cells to the site of infection).

Question 28

What does antigen sampling refer to?

Answer 28

This refers to T-cells scanning for antigen (sampling stromal cells/reticular networks) using their Ag receptor upon entering the lymph node.

Question 29

True or False?:

Naive CD4+ T-cells arrest their movements after engaging Ag:MHC. They bind to the presenting DC and slow down their movement through the lymph node. The T-cells become involved in committed, long-term (8 hours or more) relationships with DCs.

Answer 29

True

Question 30

What is the most predominant type of immune cell in the blood?

Answer 30

Neutrophils

Question 31

What key immunological process best explains the data collected between days 2-4?

• Neutrophils are being recruited to the site of infection.
• Antigen specific T-cells are being activated in the lymph node.
• Activated DCs are travelling to the local lymph node.
• Effector T-cells are at the site of infection killing infected cells.

Answer 31

Antigen specific T-cells are being activated in the lymph node.