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1

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

recirculation

2

the general process of leukocyte movement from blood into tissues

migration or recruitment

3

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

leukocyte homing

4

the recruitment of leukoycytes and plasma proteins from the blood to sites of infection and tissue injury ina

major part of the porcess of inflammation

5

What is inflammation triggered by?

recognition of microbes and dead tissue in innate immune response

6

What delivers the cells and molecules of host defense to the sites where offending agents need to be combated?

inflmmatory response

7

P-selectin (CD62P)

endothelium activated by histamine or thrombin

8

P- selectin ligand

Sialyl Lewis X on PSGL-1 and other glycoproteins; neutrophils, monocytes, T cells (effector, memory)

9

E-selectin (CD62E_ distribution

endothelium activated by cytokins (TNF, IL-1)

10

E-selectin Ligand

sialyl Lewis X (CLA-1) on glycoproteins; neutrophils, monocytes, T cells (effector, memory)

11

L-selectin (CD62L) distribution

neutrophils, monocytes, T cells (naive and central memory), B cells (naive

12

L-slectin (CD62L) ligand

sialyl lewis X/PNAd on GlyCAM-1, CD34, MadCAM-1, others; endothelium HEV

13

LFA-1(CD11aCD18) districbution

neutrophils, monocytes, T cells (naive, effector, memory), B cells (naive)

14

LFA-1 ligand

ICAM-1(ICAM

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A cascade of adhesive and activation events underlies the trafficking of all?

Subsets of circulation leukocytes

16

What can circulating leukocytes do?

Tether to and roll on the endothelium through transient interactions of seletins and integrin w their receptors

17

Rolling allows leukocytes to?

Sample the endothelium for chemokines

18

What activate integrins and trigger adhesioin to the endothelium

chemokines

19

What migraete across teh endothelium into the extravascular space?

adherent leukocytes

20

When leukocytes arive at extrvascular space,

leukocytes can migrate down chemokine gradients toward specific areas

21

What constatnly ciruclate through the blood, into tissues and often back into the blood again?

immune cells

22

What are activated by ctyokines secreted by resident Mo and mast cells at sites of infection and tissue injury?

endothelial cells

23

What is the result of activated cytokines for increased adhesion?

increased adhesiveness of the endothelial cells for ciruclating myeloid leukocytes and Ag activated effector and memory lymphocytes

24

What require the temporary adhesion of the leukocyte to the endothelial cells of blood vessels?

leukocyte/lymphocyte homing

25

What does homing involve?

molecules on the surfaces of both the leukocytes(homing receptors and chemokine receptors) and endothelia cells(chemokines)

26

What comprise a set of several adhesion molecules on the surface of endothelial cells which regulate lymphocyte recirculation via HEV?

addressins

27

What express P selectin(CD62P) and E selectin (CD62E)

endothelial cells

28

What is synthesized and expressed on the endothelial cell surface within 1 to 2 hours in response to the cytokines IL1 and TNF?

E selectin

29

What is produced by tissue macrophages in response to infections?

IL1 and TNF

30

What are the ligans for E selectins and P selectins?

complex sialylated carbohydrates

31

What is ONLY expressed on leukocytes adn lymphocytes but not on endothelial cells?

L selectins(CD62L)

32

What is L selection expression activated by?

IL1 and TNF at sites of inflammation

33

What are L selectins important for?

naive T and B lymphocytes for homing into LNs by interacting with high endothelial venules (HEV)

34

What are L selectin ligands expressed on HEV called??

peripheral node addressins (PNAd)

35

LFA-1(CD11aCD18) distribution

neutrophils, monocytes, T cells(naive, effector, memory) B cells (naive)

36

Ligand for LFA-1(CD11aCD1)

ICAM-1(CD54), ICAM-2(CD102); endothelium(cytokine-induced)

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Mac-1(CD11bCD18) distribution

neutrophils, monocytes, dendritic cells

38

Mac-1(CD11bCD18) ligand

ICAM-1(CD54), ICAM-2(CD102); endothelium(cytokine-induced)

39

VLA-4(CD49aCD29) distribution

monocytes, T cells(naive, effector, membory)

40

Ligand for VLA-4(CD49aCD29)

VCAM-1(CD106); endothelium (cytokine-induced)

41

Distribution for alpha4beta7(CD49dCD29)

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

42

Ligand for alpha4beta7

VCAM-1 MadCAM1; endothelium in gut and gut associated lymphoid tissues

43

What are integrins?

hetrodimeric cell surfac proteins
-composed of two noncovalently linked polypeptide chains

44

What doe integrins do?

mediate adhesion of cells to other cells or to extracellular matrix

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How do integrins mediate adhesion?

vaious specific ligands

46

What cause integrate signals?

extracellular ligands with cytoskeleton dependent motility, shape change, and phagocytic responds

47

How are integrins able to response to intracellular signals?

by rapidly increasing their affinity for their ligands(integrin activation)

48

Integrin activation that occurs in all leukocyres is in response to?

chemokine binding to chemokine receptors

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in T lymphocytes integrin activation occurs>?

when Ag binds to TCRs

50

What is integrin activation mediated by?

chemokine-induced conformational changes in teh extracellular domains of the integrins that lead to increased affinity

51

Why type of chemokine signaling leads to increased affinity?

inside-out signaling, which is involved in intgrin activation

52

The inegrins on blood leukocytes are nomrally

in a low affinity state

53

When rolling of leukocytes occurs, chemokines displayed on the endothelial surface?

bind chemokine receptors on the leukocytes

54

What happens when chemokine receptor signalling occurs?

activates the leukocyte integrins, increasing hteir affinity for their ligands on the endothelial cells

55

What are chemokines?

A large family of structurally homlogous cytokines of 8-10 kD that contain two internal disulfide loops

56

What do chemokines stimulate?

leukocyte movment and regulate the migration of leukocytes from the blood to tissues

57

How many human chemokines?

50, classified inot four families on number and location of N termal cystein residues

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the two defining cystein residues are adjacent

CC or Beta chemokines

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these residues are spearatied by one amino acid

CXC or alpha chemokines

60

a single cysteine

C chemokines

61

two cysteines are separated by three amino acids

CX3C chemokines

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CCL1, I-309

CCR8
-monocyte recruitment and endothelial cell migration

63

CCL2, MCP-1

CCR2
-mixed leukocyte recruitment

64

CCL2, MIP-1alpha

CCR1, CCR5
-mixed leukocyte recruitment

65

CCL4, MIP-1beta

CCR5
-T cell, dendritic cell, monocyte, and NK recuirtment; HIVE coreceptor

66

CCL5, RANTES

CCR1, CCR3, CCR5
-mixed leukocyte recruitment

67

CCL11, Eotaxin

CCR3
-Eosinophil, basophil, and TH2 recruitment

68

CCL19, MIP-3beta

CCR7
T cell and dendritic cell migration into parafollicular zones of lymph nodes

69

CCL20, MIP-3alpha

CCR6
-Th17 recruitmetn, DC positioning in tissue

70

CCL21 SLC

CCR7
-T cell and dendritic cell migration into parafollicular zones of lymph nodes

71

CCL22, MDC

CCR4
-NK cell, T cell recruitment

72

CXCL1, GROalpha

CXCR2
-neutrophil recruitment

73

CXCL5, ENA-78

CXCR2
-neutrophil

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CXCL8, IL-8

CXCR1, CXCR-2
Neutrophil recruitment

75

CXCL10, IP-10

CXCR3, CXCR3B
efector T cell recruitment

76

CXCL11, I-TAC

CXCR3, CXCR7
-effector T cell recruitment

77

CXCL12, SDF-1alpha beta

CXCR4
-mixed leukocyte recruitment; HIV coreceptor

78

CXCL13, BCA-1

CXCR5
-B cell migration into follicles; T follicular helper cell migration inot follicles

79

CXCL14 BRAK

monocyte and dendritic cell migration

80

XCL1, lymphotactin

XCR1
-T cell and NK cell recruitment

81

CX3CL1, Fractalkine

CX3CR1
-T cell, NK cell, and monocyte recruitment; CTL and NK cell activation

82

Neutrophils and monoctes circulating in the blood,

are ready to be recruited into tissue sites of infection or injury without activation

83

How do neutrohpils and monocyrtes enter tissue?

through post-capillary venules except parenchymal tissues(liver, lungs, kidney) where all blood cells enter through capillaries

84

What do myeloid leukocytes eliminate?

infectious pathogens, clear dead tissues and repair damage

85

What controls transmigration of monocytes?

CCL2 (MCP-1)

86

What further stabilizes rolling?

L-selectins binding to ligands on endothelial cells

87

What initiates rolling on the endothelium?

P selectins and ligands

88

What can be induced on the surace of endothelial cells by cytokines?

E selectin expression

89

Activated resident Mo produe?

ctokines TNF and IL-1 that induce the rapid induction of expression of pre formed P selectin on the surface of endothelial cells

90

What chemokine do endothelial cells present?

CXC-chemokine ligand 8(CXCL8 also called IL-8) that recognizes by receptors on neutrophils

91

Transmigrasion of monocytes by CCL2 activates?

leukocyte integrins and results in more stable leukocyte adhesion

92

Once leukocyte have completed trans-endothelial migration

they interact w chemokines in the underlying basement membrane

93

What do cell do following diapedesis?

adopt an amoeboid shape

94

Where are chmotactic receptors located?

the leading edge

95

once leukocytes have completed trans endothelial migrations,

they interact w chemokines in the underlying basement membrane

96

How do neutrophils migrate?

In a polarized fashion along collagen fibrils in response to a chemotactic gradient toward the site of infection/inflammation

97

The mechanisms of recuriment of neutrophils (chomkine IL-8) and monocytes (chemokine MCP) is identical except?

the difference in chemokines involved

98

preferentially leave the blood and enter peripheral tissues through venules at sites of inflammation

effector and memory T cells

99

Migration and recirculation of naive T cells

-preferntially leave the blood and enter lymph nodes across the HEV
-dendritic cells bearing Ag enter the lymph nodes through lymphatic vessels
-If the T cells recognize Ag, they are activated, and they return into the arterial ciruculation

100

L selectin is expressed by?>

T and B lymphocytes

101

How do naive lymphocytes enter the LN?

through the HEV

102

Whare are L selectin ligands expressed on HEV called?

peripheral node addressins (PNAd)

103

Without L selectins lymphocytes are unable to?

enter peripheral nodes and see the Ag

104

the naive lymphocytes enter the LN through?

an artery, leave the circuitaiton by moving across the wall of the HEV

105

What are B and T cells drawn to different zones of the LN by?

Chemokines that are produced in these areas

106

How do Ag-loaded DCs enter the LN?

through afferent lymphatic vessels come from the sites of Ag entry

107

Where doe DCs migrate in teh LN?

the T cell rich aresa

108

Nave T lyphocytes home to LN as a result of?

L selectin binding to peripheral lymph node addressin(PNAd) on HEV

109

What are present only in secondary lymphoid organs?

HEV

110

What chemokines are displayed on the surface of the HEV?

CCL19 and CCL 21

111

Chemokines binding to CCR7 activate?

integrins

112

Naive T cells have low levels of.... bc the receptor is internalized after binding S1P in the blood

S1PR1

113

Naive T cells that have recently entered a LN

cannot sense S1p concentration gradient btw the T cell zone of the node and the lymph

114

What can the naive T cell exit the cell?

S1PR1 is re expressed and the cell exit the LN

115

What have low levels of S1PR1 and the celsl stay in teh LN?

Ag activated T cells

116

after serval days S1PR1 will be re expressed and ... then sense the S1P gradient and exit the node

effector T cells

117

What home to sites of infection in peripheral tissues?

activated effector T cells

118

What is cell migration into tissue mediated by?

E selectin and P selectin, integrins, and chmokine(CXCL10) that are produced at sties of infection

119

What is important for the mobilization of effector T celsl in sites of infection and inflammation?

CD44

120

At sites of infection and inflammation, endothelial cells secrete?

chemokines and epress E and P selectin and hydronic acid

121

What can mediate rolling interation?

CD44, with vascular endothelial cellst hat express HA, its natural ligand, or even E selectin

122

Chemokine signaling via GPCRs results in increased?

integrin affinit, such as VLA-4 which enhances adhasivnbeness(inside out signaling)

123

Engagement of CD44 and HA may also trigger?

CPCR-dependent inside out upregulaitoin of VLA4VCAM bindign

124

Naive B cells use the same basic mechanisms as naive T cells to home to secondary lymphoid tissues

throughout the whole body

125

What leave the bone marrow through the blood, enter the red pulp of the spleen, and migrate to the periphery of the white pulp??

immature B cells

126

A B cells mature further, they express?

chemokine receptor CXCR5, which promotes their movement into the white pulp in response to a chemokine called CXCL13

127

once the maturation is completed within the white pulp for mature naive B cells they?

reenter the circulation and home to lymph nodes and mucosal lymphoid tissues

128

In the follicles B cells may encounter.... and becomes...

Ag, activated

129

In the stroma, B cells migrate into?

follicles dirven by CXCL13 recognized by CXCR5 expressed by naive B cells

130

What does the homing proecess require? Chemokines?

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

131

What does homing of mature naive Be cells from the blood into LNs involve?

rolling interactions on HEVs, chemokine activation of integrins, and stable arrest, as described earlier for naive T cells