Leukocyte Circulation and Migration into Tissue (Lec 3)

Question 1

Where are antigens captured and taken?

Answer 1

captured at site of infection

taken to the draining LNs where immune response is initiated

Question 2

What is recirculaiton?

Answer 2

the ability of lymphocytes to repeatedly home to secondary lymphoid organs, reside there transiently, and return to the blood

Question 3

The general process of leukocyte movement from blood into tissue is called?

Answer 3

Migration or recruitment

Question 4

What is leukocyte homing?

Answer 4

the migration of leukocyte out of the blood and into a particular tissue, or to a site of an infection or injury

Question 5

The recruitment of leukocytes and plasma proteins from the blood to sites of infection and tissue injury is a major part of the process of ____

Answer 5

inflammation

Question 6

What triggers inflammation?

Answer 6

recognition of microbes and dead tissue in innate immune responses

note: refined and prolonged durin adaptive immune responses

Question 7

True or False?
Circulating leukocytes can tether to and roll on the endothelium through transient interactions of selections and integrin with their receptors

Answer 7

true

Question 8

Rolling allows the leukocytes to search the endothelium for chemokines which…?

Answer 8

activate integrins and trigger adhesion to endothelium

Question 9

Once the leukocytes have adhered and migrated into endothelium, where do they go?

Answer 9

they migrate down chemokine gradients towards specific areas

Question 10

What activates endothelial cells at sites of infection and tissue injury?

Answer 10

cytokines secreted by resident macrophages and mast cells at these sites

Question 11

True or False?
In homing, the leukocyte surface contains homing receptors and chemokine receptors; the endothelial surface contains chemokines

Answer 11

true

Question 12

Addressins comprise a set of several adhesion molecules on the surface of endothelial cells which regulate…?

Answer 12

lymphocyte recirculation via HEV

Question 13

Which selections do endothelial cells express?

Answer 13

P-selectin and E-selectin

Question 14

How long does it take for E-selectin to be synthesized and expressed on the endothelial surface in response to the cytokines IL-1 and TNF at sites of infection?

Answer 14

within 1-2 hours

Question 15

Where is L-selectin expressed?

Answer 15

only on leukocytes and lymphocytes

Question 16

What activates L-selectin expression?

Answer 16

IL-1 and TNF at sites of inflammation

Question 17

L-selectin is important for naive T and B lymphocytes for homing into lymph nodes by interacting with ___?

Answer 17

HEV

Question 18

What are integrins? What is their function?

Answer 18

heterodimeric cell surface proteins composed of two noncovalently linked polypeptide chains. function - integrate signals triggered by extracellular ligands

Question 19

What do integrins mediate?

Answer 19

adhesion of cells to other cells or to extracellular matrix via specific ligands

Question 20

How are integrins able to respond to intracellular signals?

Answer 20

by rapidly increasing their affinity for their ligands

Question 21

Integrin activation occurs when…?

Answer 21

in response to chemokine binding to chemokine receptors

In T lymphocytes, integrin activation occurs when antigen binds to TCRs.

Question 22

True or False?

Chemokines contain two internal disulfide loops?

Answer 22

true

Question 23

CC or Beta chemokines

Answer 23

two defining cysteine residues are adjacent

Question 24

CXC or alpha chemokines

Answer 24

residues are separated by one amino acid

Question 25

C chemokines

Answer 25

there is a single cysteine

Question 26

CX3 C chemokines

Answer 26

two cysteines are separated by three amino acids

Question 27

Neutrophils and monocytes arise in the ___ ___ and circulate in the ____

Answer 27

bone marrow; blood

Question 28

True or False? | neutrophils and monocytes require activation

Answer 28

false

Question 29

The interaction between P-selectin and ligands on leukocytes initiates what?

Answer 29

rolling on the endothelium

Question 30

Rolling is further by...?

Answer 30

L-selectin binding to ligands on endothelial cells

Question 31

IL-8 is recognized by..?

Answer 31

receptors on neutrophils

Question 32

CCL2 (MCP-1) controls what?

Answer 32

transmigration of monocytes

Question 33

Once leukocytes have completed trans-endothelial migration, they interact with _____ in the underlying basement membrane.

Answer 33

chemokines

Question 34

Chemotactic receptors are located where?

Answer 34

the leading edge

Question 35

Naive T cells preferentially leave the blood and enter ___ ___ across HEV.

Answer 35

lymph nodes

Question 36

DCs bearing antigens enter the lymph nodes through _____ ______.

Answer 36

lymphatic vessles

Question 37

If T cells recognize an antigen, what happens?

Answer 37

they are activated and return to the arterial circulation

Question 38

Effector and memory T cells preferentially leave the blood and enter _____ ______ through venues at sites of inflammation.

Answer 38

peripheral tissues

Question 39

True or False? L-selectin is expressed by both T and B lymphocytes although two types of lymphocytes utilize a distinct cell adhesion molecules.

Answer 39

true

Question 40

How do naive lymphocytes enter the LNs?

Answer 40

through the HEV

Question 41

L-selectin expressed on HEV is called what?

Answer 41

peripharal node addresins (PNAd)

Question 42

The naive lymphocytes enter the LN through an artery, and leave the circulation by...?

Answer 42

moving across the wall of the HEV

Question 43

HEV are present only in....?

Answer 43

secondary lymphoid organs

Question 44

Chemokines CCL19 and CCL21 are displayed where?

Answer 44

the surface of the HEV

Question 45

Chemokines binding to CCR7 activates what?

Answer 45

integrins

Question 46

Why do Naive T cells have low levels of S1PR1?

Answer 46

because the receptor is internalized after binding S1P in the blood

Question 47

Naive T cells that have recently entered a LN cannot sense S1P concentration gradient between what two areas?

Answer 47

between the T cell zone of the node and the lymph

Question 48

True or False? | antigen-activated T cells have low levels of S1PR1 and the cells stay in the LN.

Answer 48

True

Question 49

True or False? S1PR1 is re-expressed after several days and activated and differentiated effector T cells then sense the S1P gradient and exit the node.

Answer 49

true

Question 50

Activated effector T cells home to...?

Answer 50

sites of infection in peripheral tissue

Question 51

cell migration into tissue is mediated by...?

Answer 51

E-selctin and P-selectin, integrins, and chemokine (CXCL10) that are produced at sites of infection

Question 52

Many chemokines and chemokine receptors are involved in....?

Answer 52

effector/memory T cell migration

Question 53

CD44 is important for?

Answer 53

the mobilization of effector T cells in sites of infection and inflammation note: CD44 can mediate rolling interactions with vascular endothelial cells that express hyaluronic acid, its natural ligand, or even E-selectin

Question 54

Chemokine signaling via GPCRs results in?

Answer 54

increased integrin affinity ("inside-out" signaling)

Question 55

Engagement of CD44 with HA may also trigger what?

Answer 55

GPCR-dependent "inside-out" up regulation of VLA-4-VCAM binding

Question 56

Immature B cells leave the bone marrow through the ____, enter the ______, and migrate to the periphery of the ____

Answer 56

blood; red pulp of the spleen; white pulp note: as they mature further, the B cells express the chemokine receptor CXCR5, which promotes their movement into the white pulp in response to a chemokine called CXCL13

Question 57

Once the maturation is complete within the white pulp, mature naive B cells reenter the circulation and home to _____ and ____

Answer 57

lymph nodes; mucosal lymphoid tissues

Question 58

True or False? Homing of mature naive B cells from the blood into LNs involves rolling interactions on HEVs, chemokine activation of integrins, and stable arrest.

Answer 58

true, same as for naive T cells

Question 59

Homing process requires what chemokines on HEV?

Answer 59

CXCL12 and CCL19/CCL21 on HEV and their chemokine receptors CXCR4 and CCR7 on naive B cells.