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Immunology > Leukocyte Circulation and Migration into Tissue > Flashcards

Leukocyte Circulation and Migration into Tissue Flashcards

1
Q

migration or recruitment is the general process of leukocytes

A

movement from blood into tissues

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2
Q

recirculation is the ability of lymphocytes to repeatedly:

A
  1. home to secondary lymphoid organs
  2. reside in secondary lymphoid organs transiently
  3. return to the blood
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3
Q

leukocyte homing is

A

cell migration out of the blood and into peripheral tissues. mostly occurs in response to an infection or tissue injury

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4
Q

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

A

inflammation

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5
Q

inflammation is triggered by

A

recognition of microbes and dead/injured tissues in innate immune responses and is refined and prolonged during adaptive immune responses

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6
Q

neutrophils and monocytes arise in the

A

bone marrow and circulate in the blood

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7
Q

neutrophils and monocytes are ready to be recruited into tissues sites of infection and injury with or without activation

A

without activation

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8
Q

neutrophils and monocytes enter the tissue through _____ except parenchymal tissues (liver, lungs, kidneys) where all blood cells enter through _____

A

post-capillary venules

capillaries

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9
Q

functions of myeloid leukocytes

A

eliminate infectious pathogens

clear dead tissues

repair the damage

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10
Q

leukocyte recruitment: a cascade of adhesive and activation events underlies the trafficking of all subsets of of circulating leukocytes including:

A
  1. tethering: transient interactions of selectins and integrins with their ligands
  2. rolling: chemokine receptors on leukocytes to bind chemokine expressed on endothelium
  3. adhesion and arrest: receptors signal and activate integrins on leukocytes which interact with ligands on endothelium and trigger adhesion/arrest to the endothelium
  4. transmigration into the tissue: leukocytes then transmigrate into the extravascular space where they follow chemokine gradients towards areas of infection and/or tissue damage
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11
Q

once leukocytes have completed trans-endothelial migration, they

A

interact with chemokines in the underlying basement membrane

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12
Q

following diapedesis, cells adopt _____ shape

A

an amoeboid

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13
Q

transmigration of leukocyte:

capture and rolling of cells involves

A

selectins

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14
Q

transmigration of leukocytes:

activation (rolling -> adhesion) involves

A

chemokines

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15
Q

transmigration of leukocytes:

firm adhesion involves

A

adhesion molecules

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16
Q

after diapedesis, leukocytes migrates in a polarized fashion along

A

collagen fibrils in response to a chemotactic gradient toward the site of infection/inflammation

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17
Q

chemotactic receptors are located where on the migrating leukocyte

A

on the leading edge

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18
Q

endothelial cells in _____ tissues do not express adhesion molecules on their surfaces facing the blood

A

healthy

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19
Q

tissue recruitment of immune cells:

endothelial cells at sites of infection and/or tissue injury

A
  1. are activated by cytokines locally secreted by resident immune cells (mast cells and macrophages)
  2. express adhesion molecules
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20
Q

tissue recruitment of immune cells:

the consequence of activated endothelial cells is the increased adhesiveness for circulating _____ and _____

A

leukocytes (neutrophils, monocytes, basophils, and eosinophils)

antigen-activated (not naive) lymphocytes (T and B cells)

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21
Q

tissue recruitment of immune cells:

leukocyte/lymphocyte homing/recruitment requires the temporary

A

adhesion of the leukocyte/lymphocyte to the endothelial cells of blood vessels

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22
Q

homing involves molecules on the surfaces of both the _____ and _____

A

leukocyte/lymphocyte (homing receptors and chemokine receptors)

endothelial cells (chemokines)

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23
Q

addressins comprise a set of adhesion molecules expressed only on the surface of

A

high endothelial venules (HEV)

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24
Q

selectins provide _____ interactions with their ligands

A

low affinity

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25
Q

the selectins (E and P selectins) are a family of glycoproteins that mediate low-affinity endothelial-leukocyte interactions, thus promoting the

A

tethering and rolling of leukocytes through interactions with specific ligands on leukocytes

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26
Q

only ____ endothelial cells express P-selectin and E-selectin

A

activated

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27
Q

P-selectin is pre-synthesized by

A

unactivated endothelial cells and stored in granules which promptly move to the surface in activated endothelial cells

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28
Q

when is E-selectin is synthesized and expressed on the endothelial cell surface

A

within 1-2 hours in responses to histamine, thrombin, and inflammatory cytokines (IL-1 and TNF) produced by mast cells and tissue macrophages in response to infection/tissue injury

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29
Q

the ligands for E-selectin and P-selectin are ______ on innate immune cells (neutrophils, monocytes, eosinophils, and basophils) as a complex sialylated carbohydrates related to the ______

A

constitutively expressed

Lewis X antigen

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30
Q

L-selectin is most important for

A

homing of naive T and B lymphocytes into lymph nodes by interacting with HEV but it also has an accessory function in inflammation

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31
Q

L-selectin ligands expressed on HEV is called

A

peripheral node addressins (PNAd)

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32
Q

integrins provide a ____ affinity interaction with their ligands

A

high

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33
Q

functions of integrins

A

integrate signals triggered by extracellular ligands with cytoskeleton-dependent motility, shape change, and phagocytic responses

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34
Q

there are more than _____ different integrins, all with the same basic structure

A

30

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35
Q

integrins mediate _____ of cells to other cells or to extracellular matrix via various specific ligands

A

adhesion

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36
Q

all leukocytes, including B and T cells, monocytes, macrophages, neutrophils, basophils, and eosinophils express the integrin _____

A

lymphocyte function-associated antigen 1 (LFA-1)

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37
Q

integrin Lymphocyte function-associated antigen 1 (LFA-1) binds its ligand _____ and _____, which is expressed on _____

A

ICAM-1

ICAM-2

cytokine-activated endothelial cells

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38
Q

leukocytes also express integrin Very Late Antigen-4 that binds to _____, which is expressed on _____

A

VCAM-1

cytokine-activated endothelial cells

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39
Q

integrin alpha4beta7 binds to _____ and ______ which are found on _____

A

VCAM-1 and MadCAM

endothelium in gut and associated lymphoid tissue

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40
Q

integrin Mac-1 binds to ligand _____ and _____ on _____

A

ICAM-1

ICAM-2

cytokine-activated endothelial cells

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41
Q

integrins are able to respond to intracellular signals by rapidly increasing their affinity (integrin activation), this occurs in all leukocytes in response to

A

chemokine binding to chemokine receptors

42
Q

integrin activation is mediated by chemokine-induced conformational changes in the extracellular domains of the integrins that lead to

A

an increased affinity

43
Q

signaling involved in integrin activation

A

inside-out signaling

44
Q

the integrins on blood leukocytes are normally in a _____ state

A

low-affinity

45
Q

when rolling of leukocytes occurs, chemokines displayed on the endothelial surface can bind

A

chemokine receptors on the leukocyte

46
Q

chemokine receptor signaling occurs, which

A

activates integrins of leukocytes, increasing their affinity for their ligands on the endothelial cells

47
Q

bent conformation of leukocyte integrin

A

low-affinity

48
Q

extended conformation of leukocyte integrin

A

high-affinity

49
Q

chemokines are a large family of structurally _____ cytokines

A

homologous

50
Q

the name chemokine is a contraction of

A

CHEMOtactic and cytoKINE

51
Q

chemokines stimulate leukocyte _____ and regulate the _____ of leukocytes from the blood to tissue

A

movement

migration

52
Q

C chemokines

A

single cysteine

53
Q

CC or Beta chemokines

A

2 defining cysteine residues are adjacent

54
Q

CXC or alpha chemokines

A

cysteine residues are separated by amino acid

55
Q

CX3C chemokines

A

2 cysteines are separated by 3 amino acids

56
Q

MALT

A

mucosa-associated lymphoid tissue (gut)

57
Q

42 percent of all lymphocytes at a given point in time are found

A

in the lymph nodes and stay there on average about 12 hours

58
Q

45 percent of all lymphocytes at a given point in time are found

A

in the spleen and stay there on average about 5 hours

59
Q

lymphocytes are in circulation roughly ____ min

A

30

60
Q

10 percent of all lymphocytes at a given point in time are found

A

in the MALT

61
Q

naive T cells preferentially leave the blood and enter

A

lymph nodes across the HEV

62
Q

dendritic cells bearing antigen enter the lymph nodes through

A

afferent lymphatic vessels

63
Q

if T cells recognize their antigen, they are activated, and

A

return into circulation leaving the LN via efferent lymphatic vessels

64
Q

effector and memory T cells preferentially leave the blood and enter peripheral tissues through

A

venules at sites of inflammation

65
Q

unlike E and P selectins which are expressed on activated endothelial cells, L-selectin is

A

strongly and constitutively expressed by naive T and B lymphocytes

66
Q

L-selectin deficient lymphocytes are unable to

A

enter peripheral nodes and “see” the antigen

67
Q

naive lymphocytes enter the lymph nodes through the _____ which express ______

A

HEV

selective Ligands for L-selectin

68
Q

L-selectin ligands expressed on HEV have been collectively called _____

A

peripheral node addressins (PNAd)

69
Q

lymphocytes that did not find their antigen leave the lymph nodes via

A

efferent lymphatics and enter downstream lymph nodes

70
Q

P-selectin is expressed where

A

on activated endothelium

71
Q

ligand for P-selectin is expressed

A

constitutively on innate immune cells (neutrophils, monocytes, eosinophils, and basophils; and on activated lymphocytes as a complex sialylated carbohydrates related to the Lewis X antigen

72
Q

ligand for E-selectin is expressed

A

constitutively on innate immune cells (neutrophils, monocytes, eosinophils, and basophils; and on activated lymphocytes as a complex sialylated carbohydrates related to the Lewis X antigen

73
Q

E-selected is expressed

A

on activated endothelium

74
Q

L-selectin is expressed

A

mostly on lymphocytes

75
Q

ligands for L-selectin is expressed

A

on HEV and is called peripheral node addressins (PNAs)

76
Q

what cells express Mac-1 integrin

A

neutrophils, monocytes, DCs

77
Q

what cells express alpha4beta7 integrin

A

monocytes, T cells (gut homing, naive, effector, memory), B cells (gut homing)

78
Q

naive lymphocytes enter the LN through an artery, leaving the circulation by moving across the wall of the

A

HEV

79
Q

Ag-loaded DCs enter the LN through

A

afferent lymphatic vessels coming from the site of Ag entry

80
Q

Ag-loaded DCs migrate where in the LN

A

to the T cell-rich areas

81
Q

naive T/B cells that didn’t find their Ags in the LNs leave it via

A

efferent lymphatic vessel to migrate to other LNs without entering the circulation

82
Q

chemokines CCL19 and CCL21 are displayed on the surface of

A

HEV

83
Q

chemokines CCL19 and CCL21 bind to chemoreceptors ______ and activates integrins

A

CCR7

84
Q

chemokine CXCL8

original name

major function

A

IL-8

neutrophil recruitment

85
Q

chemokine CCL2

original name

major function

A

MCP-1

mixed leukocyte recruitment (monocytes)

86
Q

chemokine CCL19

original name

major function

A

MIP-3beta

T cell and DC migration into parafollicular zones (T-cell zone) of lymph nodes

87
Q

chemokine CCL21

original name

major function

A

SLC

T cell and DC migration into parafollicular zones (T-cell zone) of lymph nodes

88
Q

naive T cells spend approx _______ surveying a LN for specific Ag and if undetected, they transmigrate into cortical or medullary sinuses and exit through ______

A

6-12 hours

efferent LV

89
Q

naive T cells express low levels of ______ because the receptor is internalized after binding _____ which has high concentration in the blood

A

S1PR1

S1P

90
Q

naive T cells that have recently entered a LN cannot sense the S1P concentration gradient between the T cell zone of the lymph node and the lymph and therefore do NOT leave the LN, they cannot exit the node for several hours until ______ is re-expressed and the cell can exit the LN by mechanism of chemotaxis

A

S1PR1

91
Q

Ag-activated T cells continue to express low levels of S1PR1 and stay in the LN for several days, S1PR1 is re-expressed on Ag-activated T cells after several days and activated and differentiated effector T cells then

A

sense the S1P gradient and exit the node

92
Q

activated effector T cells home to

A

sites of infection in peripheral tissues

93
Q

cell migration into tissue is mediated by

A

E-selectin, P-selectin, and activated integrins (by chemokines)

94
Q

chemokine CCL4

original name

major function

A

MIP-1beta

T cell, DC, monocyte, and NK recruitment; HIV coreceptor

95
Q

chemokine CXCL10

original name

major function

A

IP-10

effector T cell recruitment

96
Q

immature naive B cells leave the bone marrow through the blood and enter the _______ and migrate to the

A

red pulp of the spleen

periphery of the white pulp

97
Q

maturation of B cells occurs in the

A

white pulp of the spleen

98
Q

mature naive B cells reenter the circulation (after maturing in the white pulp of the spleen) and home to

A

LNs and mucosal lymphoid tissues

99
Q

mature naive B cells use the same basic mechanisms mediated by L-selectin for homing of mature naive B cells from the blood into LNs including rolling mediated by

A

interactions with L-selectin ligands expressed on HEVs, chemokine dependent activation of integrins, and stable arrest just as naive T cells

100
Q

chemokine CXCL12

original name

major function

A

SDF-1alphabeta

homing naive B cells to LNs;

activation of integrins requires CXCL12 expressed on HEV and their chemokine receptors

101
Q

chemokine CXCL13

original name

major function

A

BCA-1

B cell migration into follicles; T follicular helper cell migration into follicles

102
Q

in follicles, if B cells encounter their Ag, they become

A

activated

Immunology (23 decks)

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