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Undeleted > Lecture 3 > Flashcards

Lecture 3 Flashcards

1
Q

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

A

recirculation

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2
Q

the general process of leukocyte movement from blood into tissues

A

migration or recruitment

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3
Q

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

A

leukocyte homing

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4
Q

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

A

major part of the porcess of inflammation

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5
Q

What is inflammation triggered by?

A

recognition of microbes and dead tissue in innate immune response

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6
Q

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

A

inflmmatory response

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7
Q

P-selectin (CD62P)

A

endothelium activated by histamine or thrombin

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8
Q

P- selectin ligand

A

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

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9
Q

E-selectin (CD62E_ distribution

A

endothelium activated by cytokins (TNF, IL-1)

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10
Q

E-selectin Ligand

A

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

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11
Q

L-selectin (CD62L) distribution

A

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

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12
Q

L-slectin (CD62L) ligand

A

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

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13
Q

LFA-1(CD11aCD18) districbution

A

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

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14
Q

LFA-1 ligand

A

ICAM-1(ICAM

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15
Q

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

A

Subsets of circulation leukocytes

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16
Q

What can circulating leukocytes do?

A

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

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17
Q

Rolling allows leukocytes to?

A

Sample the endothelium for chemokines

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18
Q

What activate integrins and trigger adhesioin to the endothelium

A

chemokines

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19
Q

What migraete across teh endothelium into the extravascular space?

A

adherent leukocytes

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20
Q

When leukocytes arive at extrvascular space,

A

leukocytes can migrate down chemokine gradients toward specific areas

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21
Q

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

A

immune cells

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22
Q

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

A

endothelial cells

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23
Q

What is the result of activated cytokines for increased adhesion?

A

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

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24
Q

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

A

leukocyte/lymphocyte homing

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25
Q

What does homing involve?

A

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

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26
Q

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

A

addressins

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27
Q

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

A

endothelial cells

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28
Q

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

A

E selectin

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29
Q

What is produced by tissue macrophages in response to infections?

A

IL1 and TNF

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30
Q

What are the ligans for E selectins and P selectins?

A

complex sialylated carbohydrates

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31
Q

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

A

L selectins(CD62L)

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32
Q

What is L selection expression activated by?

A

IL1 and TNF at sites of inflammation

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33
Q

What are L selectins important for?

A

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

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34
Q

What are L selectin ligands expressed on HEV called??

A

peripheral node addressins (PNAd)

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35
Q

LFA-1(CD11aCD18) distribution

A

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

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36
Q

Ligand for LFA-1(CD11aCD1)

A

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

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37
Q

Mac-1(CD11bCD18) distribution

A

neutrophils, monocytes, dendritic cells

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38
Q

Mac-1(CD11bCD18) ligand

A

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

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39
Q

VLA-4(CD49aCD29) distribution

A

monocytes, T cells(naive, effector, membory)

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40
Q

Ligand for VLA-4(CD49aCD29)

A

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

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41
Q

Distribution for alpha4beta7(CD49dCD29)

A

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

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42
Q

Ligand for alpha4beta7

A

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

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43
Q

What are integrins?

A

hetrodimeric cell surfac proteins

-composed of two noncovalently linked polypeptide chains

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44
Q

What doe integrins do?

A

mediate adhesion of cells to other cells or to extracellular matrix

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45
Q

How do integrins mediate adhesion?

A

vaious specific ligands

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46
Q

What cause integrate signals?

A

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

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47
Q

How are integrins able to response to intracellular signals?

A

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

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48
Q

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

A

chemokine binding to chemokine receptors

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49
Q

in T lymphocytes integrin activation occurs>?

A

when Ag binds to TCRs

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50
Q

What is integrin activation mediated by?

A

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

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51
Q

Why type of chemokine signaling leads to increased affinity?

A

inside-out signaling, which is involved in intgrin activation

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52
Q

The inegrins on blood leukocytes are nomrally

A

in a low affinity state

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53
Q

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

A

bind chemokine receptors on the leukocytes

54
Q

What happens when chemokine receptor signalling occurs?

A

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

55
Q

What are chemokines?

A

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

56
Q

What do chemokines stimulate?

A

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

57
Q

How many human chemokines?

A

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

58
Q

the two defining cystein residues are adjacent

A

CC or Beta chemokines

59
Q

these residues are spearatied by one amino acid

A

CXC or alpha chemokines

60
Q

a single cysteine

A

C chemokines

61
Q

two cysteines are separated by three amino acids

A

CX3C chemokines

62
Q

CCL1, I-309

A

CCR8

-monocyte recruitment and endothelial cell migration

63
Q

CCL2, MCP-1

A

CCR2

-mixed leukocyte recruitment

64
Q

CCL2, MIP-1alpha

A

CCR1, CCR5

-mixed leukocyte recruitment

65
Q

CCL4, MIP-1beta

A

CCR5

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

66
Q

CCL5, RANTES

A

CCR1, CCR3, CCR5

-mixed leukocyte recruitment

67
Q

CCL11, Eotaxin

A

CCR3

-Eosinophil, basophil, and TH2 recruitment

68
Q

CCL19, MIP-3beta

A

CCR7

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

69
Q

CCL20, MIP-3alpha

A

CCR6

-Th17 recruitmetn, DC positioning in tissue

70
Q

CCL21 SLC

A

CCR7

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

71
Q

CCL22, MDC

A

CCR4

-NK cell, T cell recruitment

72
Q

CXCL1, GROalpha

A

CXCR2

-neutrophil recruitment

73
Q

CXCL5, ENA-78

A

CXCR2

-neutrophil

74
Q

CXCL8, IL-8

A

CXCR1, CXCR-2

Neutrophil recruitment

75
Q

CXCL10, IP-10

A

CXCR3, CXCR3B

efector T cell recruitment

76
Q

CXCL11, I-TAC

A

CXCR3, CXCR7

-effector T cell recruitment

77
Q

CXCL12, SDF-1alpha beta

A

CXCR4

-mixed leukocyte recruitment; HIV coreceptor

78
Q

CXCL13, BCA-1

A

CXCR5

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

79
Q

CXCL14 BRAK

A

monocyte and dendritic cell migration

80
Q

XCL1, lymphotactin

A

XCR1

-T cell and NK cell recruitment

81
Q

CX3CL1, Fractalkine

A

CX3CR1

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

82
Q

Neutrophils and monoctes circulating in the blood,

A

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

83
Q

How do neutrohpils and monocyrtes enter tissue?

A

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

84
Q

What do myeloid leukocytes eliminate?

A

infectious pathogens, clear dead tissues and repair damage

85
Q

What controls transmigration of monocytes?

A

CCL2 (MCP-1)

86
Q

What further stabilizes rolling?

A

L-selectins binding to ligands on endothelial cells

87
Q

What initiates rolling on the endothelium?

A

P selectins and ligands

88
Q

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

A

E selectin expression

89
Q

Activated resident Mo produe?

A

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

90
Q

What chemokine do endothelial cells present?

A

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

91
Q

Transmigrasion of monocytes by CCL2 activates?

A

leukocyte integrins and results in more stable leukocyte adhesion

92
Q

Once leukocyte have completed trans-endothelial migration

A

they interact w chemokines in the underlying basement membrane

93
Q

What do cell do following diapedesis?

A

adopt an amoeboid shape

94
Q

Where are chmotactic receptors located?

A

the leading edge

95
Q

once leukocytes have completed trans endothelial migrations,

A

they interact w chemokines in the underlying basement membrane

96
Q

How do neutrophils migrate?

A

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

97
Q

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

A

the difference in chemokines involved

98
Q

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

A

effector and memory T cells

99
Q

Migration and recirculation of naive T cells

A
  • 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
Q

L selectin is expressed by?>

A

T and B lymphocytes

101
Q

How do naive lymphocytes enter the LN?

A

through the HEV

102
Q

Whare are L selectin ligands expressed on HEV called?

A

peripheral node addressins (PNAd)

103
Q

Without L selectins lymphocytes are unable to?

A

enter peripheral nodes and see the Ag

104
Q

the naive lymphocytes enter the LN through?

A

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

105
Q

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

A

Chemokines that are produced in these areas

106
Q

How do Ag-loaded DCs enter the LN?

A

through afferent lymphatic vessels come from the sites of Ag entry

107
Q

Where doe DCs migrate in teh LN?

A

the T cell rich aresa

108
Q

Nave T lyphocytes home to LN as a result of?

A

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

109
Q

What are present only in secondary lymphoid organs?

A

HEV

110
Q

What chemokines are displayed on the surface of the HEV?

A

CCL19 and CCL 21

111
Q

Chemokines binding to CCR7 activate?

A

integrins

112
Q

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

A

S1PR1

113
Q

Naive T cells that have recently entered a LN

A

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

114
Q

What can the naive T cell exit the cell?

A

S1PR1 is re expressed and the cell exit the LN

115
Q

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

A

Ag activated T cells

116
Q

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

A

effector T cells

117
Q

What home to sites of infection in peripheral tissues?

A

activated effector T cells

118
Q

What is cell migration into tissue mediated by?

A

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

119
Q

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

A

CD44

120
Q

At sites of infection and inflammation, endothelial cells secrete?

A

chemokines and epress E and P selectin and hydronic acid

121
Q

What can mediate rolling interation?

A

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

122
Q

Chemokine signaling via GPCRs results in increased?

A

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

123
Q

Engagement of CD44 and HA may also trigger?

A

CPCR-dependent inside out upregulaitoin of VLA4VCAM bindign

124
Q

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

A

throughout the whole body

125
Q

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

A

immature B cells

126
Q

A B cells mature further, they express?

A

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

127
Q

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

A

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

128
Q

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

A

Ag, activated

129
Q

In the stroma, B cells migrate into?

A

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

130
Q

What does the homing proecess require? Chemokines?

A

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

131
Q

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

A

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

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