Overview of Adaptive Immune Response

Question 1

Immune function depends on circulating ______ to move from blood into tissues via the ________.

Answer 1

Leukocytes; Endothelium

Question 2

Why do naïve lymphocytes migrate from the blood to secondary organs?

Answer 2

To survey for antigens.

Question 3

List a few secondary organs/systems.

Answer 3

Spleen. Lymph nodes. Peyer’s patches.

Question 4

What types of cells migrate across inflames endothelium into infected tissue to fight infection?

Answer 4

Neutrophils. Monocytes. Effector lymphocytes.

Question 5

List the multi-step model of lymphocyte recruitment into lymph nodes.

Answer 5

1. Tethering and rolling by selectins (mucins ligands)
2. Adhesion triggering by chemokines
3. Firm adherence by integrins/ligands
4. Extravasation/Diapedesis (slipping thru endothelium)

Question 6

What are selectins? Which step in the lymphocyte recruitment are they involved in?

Answer 6

Special type of lectins, which are proteins that bind carbohydrate (sugar) ligands. They function in the earliest step of leukocyte binding to epithelium.

Question 7

L-selectin functions in what? E-selectins, P-selectins?

Answer 7

In migration into lymphoid organs; allow leukocyte binding to inflamed endothelium.

Question 8

What are chemokines?

Answer 8

Chemoattractant cytokines.

Question 9

How do chemokines promote cell adhesion to endothelium?

Answer 9

By triggering integrin activation.

Question 10

What is the main goal for chemokines?

Answer 10

To get immune cells into lymphoid tissue or sites of inflammation.

Question 11

What are integrins?

Answer 11

Transmembrane proteins on leukocytes that can be in inactive (low affinity for ligand) and active states.

Question 12

Integrins are located on ______ only.

Answer 12

Leukocytes.

Question 13

What signals leukocyte integrins into their active state? How does their shape change?

Answer 13

Signals from chemokine receptors; their shape goes from a bent ball and stick to a straight up ball and stick.

Question 14

What are integrins required for?

Answer 14

For firm adhesion to endothelium and subsequent transmigration.

Question 15

What do lymphocytes enter lymph nodes through?

Answer 15

Through blood vessels known as High Endothelial Venules (HEV).

Question 16

What region produces B cell attracting chemokines? T-zone and dendritic cell attracting chemokines?

Answer 16

B-zones; T-zones

Question 17

How do immature “sentinel” dendritic cells sample the environment for antigens?

Answer 17

Present in most tissues sampling microenvironment for antigens by pinocytosis and phagocytosis.

Question 18

What causes DCs to mature?

Answer 18

Detection of danger signals (LPS, viral RNA, bacterial DNA) or inflammatory cytokines (TNF, IL-1).

Question 19

What happens to DCs as they mature?

Answer 19

Decrease in adhesion to local tissues (keratinocytes), increase expression of receptors for chemokines made by lymphatic endothelial cells and lymphoid organ T zones, upregulate MHC and costimulatory molecules.

Question 20

Where do DCs migrate to when they mature?

Answer 20

Into lymphoid T-zone baring antigen and interact with T-cells.

Question 21

B-cells bind intact antigen through what receptor?

Answer 21

Their surface Ig/B cell receptor = BCR

Question 22

In what medium can B cells bind antigens?

Answer 22

They can bind antigens directly in blood or free antigen that is filtered through the lymphoid tissue.

Question 23

Describe the early events in B cell responses to protein antigens.

Answer 23

Antigen presentation:

1. T-cell activation
2. Migration of activated T cells to edge of follicle
3. B-cell antigen presentation
4. Bi-directinal T-B activation
5. Antigen uptake and processing
6. B-cell activation
7. Migration of activated B-cells to edge of follicle

Question 24

Describe the mechanisms of helper T-cell mediated activation of B lymphocytes.

Answer 24

1. B-cell presents antigen to helper T cell
2. T cell is activated
3. Expresses CD40L, secretes cytokines
4. B-cells are activated by CD40 engagement, cytokines
5. B-cell proliferation & differentiation

Question 25

What stops activated T-cells that have exited lymphoid tissue into the blood from re-entering lymphoid tissue?

Answer 25

Reduced ability to re-enter due to changed surface molecules.

Question 26

T-cells increased ability to enter inflamed tissue is due to increased expression of?

Answer 26

• Receptors for inflammatory chemokines
• Adhesion molecules (i.e. integrin alpha-4-beta-7)
• Ligands for adhesion molecules expressed on inflamed endothelium (i.e. E- and P-selectins)

Question 27

How are effector T-cells attracted to sites of injury/infection?

Answer 27

In response to cytokines produced by tissue cells exposed to microbial products (i.e. epithelial cells, keratinocytes, mast cells, macrophages).

Question 28

What types of cells can express MHC class I and can be recognized/killed by effector CD8 T cells.

Answer 28

All cells except RBCs.

Question 29

Macrophages and Dendritic cells in tissue present antigens to what type of T-cells?

Answer 29

To CD4 T-cells.

Question 30

CD4 T cells deliver signals that promote what?

Answer 30

1. Bacterial activity of macrophages (increase NO activity)

2. Promote further recruitment of effector cells (more T-cells, neutrophils, eosinophils, monocytes).