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Immunology > Leukocyte Circulation and Migration into Tissue (Lec 3) > Flashcards

Leukocyte Circulation and Migration into Tissue (Lec 3) Flashcards

1
Q

Where are antigens captured and taken?

A

captured at site of infection

taken to the draining LNs where immune response is initiated

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2
Q

What is recirculaiton?

A

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

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3
Q

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

A

Migration or recruitment

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4
Q

What is leukocyte homing?

A

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

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5
Q

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 ____

A

inflammation

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6
Q

What triggers inflammation?

A

recognition of microbes and dead tissue in innate immune responses

note: refined and prolonged durin adaptive immune responses

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7
Q

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

A

true

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8
Q

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

A

activate integrins and trigger adhesion to endothelium

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9
Q

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

A

they migrate down chemokine gradients towards specific areas

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10
Q

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

A

cytokines secreted by resident macrophages and mast cells at these sites

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11
Q

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

A

true

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12
Q

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

A

lymphocyte recirculation via HEV

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13
Q

Which selections do endothelial cells express?

A

P-selectin and E-selectin

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14
Q

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?

A

within 1-2 hours

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15
Q

Where is L-selectin expressed?

A

only on leukocytes and lymphocytes

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16
Q

What activates L-selectin expression?

A

IL-1 and TNF at sites of inflammation

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17
Q

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

A

HEV

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18
Q

What are integrins? What is their function?

A

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

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19
Q

What do integrins mediate?

A

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

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20
Q

How are integrins able to respond to intracellular signals?

A

by rapidly increasing their affinity for their ligands

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21
Q

Integrin activation occurs when…?

A

in response to chemokine binding to chemokine receptors

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

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22
Q

True or False?

Chemokines contain two internal disulfide loops?

A

true

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23
Q

CC or Beta chemokines

A

two defining cysteine residues are adjacent

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24
Q

CXC or alpha chemokines

A

residues are separated by one amino acid

25
Q

C chemokines

A

there is a single cysteine

26
Q

CX3 C chemokines

A

two cysteines are separated by three amino acids

27
Q

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

A

bone marrow; blood

28
Q

True or False?

neutrophils and monocytes require activation

A

false

29
Q

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

A

rolling on the endothelium

30
Q

Rolling is further by…?

A

L-selectin binding to ligands on endothelial cells

31
Q

IL-8 is recognized by..?

A

receptors on neutrophils

32
Q

CCL2 (MCP-1) controls what?

A

transmigration of monocytes

33
Q

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

A

chemokines

34
Q

Chemotactic receptors are located where?

A

the leading edge

35
Q

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

A

lymph nodes

36
Q

DCs bearing antigens enter the lymph nodes through _____ ______.

A

lymphatic vessles

37
Q

If T cells recognize an antigen, what happens?

A

they are activated and return to the arterial circulation

38
Q

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

A

peripheral tissues

39
Q

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

A

true

40
Q

How do naive lymphocytes enter the LNs?

A

through the HEV

41
Q

L-selectin expressed on HEV is called what?

A

peripharal node addresins (PNAd)

42
Q

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

A

moving across the wall of the HEV

43
Q

HEV are present only in….?

A

secondary lymphoid organs

44
Q

Chemokines CCL19 and CCL21 are displayed where?

A

the surface of the HEV

45
Q

Chemokines binding to CCR7 activates what?

A

integrins

46
Q

Why do Naive T cells have low levels of S1PR1?

A

because the receptor is internalized after binding S1P in the blood

47
Q

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

A

between the T cell zone of the node and the lymph

48
Q

True or False?

antigen-activated T cells have low levels of S1PR1 and the cells stay in the LN.

A

True

49
Q

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.

A

true

50
Q

Activated effector T cells home to…?

A

sites of infection in peripheral tissue

51
Q

cell migration into tissue is mediated by…?

A

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

52
Q

Many chemokines and chemokine receptors are involved in….?

A

effector/memory T cell migration

53
Q

CD44 is important for?

A

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

54
Q

Chemokine signaling via GPCRs results in?

A

increased integrin affinity (“inside-out” signaling)

55
Q

Engagement of CD44 with HA may also trigger what?

A

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

56
Q

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

A

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

57
Q

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

A

lymph nodes; mucosal lymphoid tissues

58
Q

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.

A

true, same as for naive T cells

59
Q

Homing process requires what chemokines on HEV?

A

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

Immunology (12 decks)

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