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IMMUNOLOGY Exam #1- Lo > Lec 03- Leukocyte Circulation and Migration into Tissue > Flashcards

Lec 03- Leukocyte Circulation and Migration into Tissue Flashcards

1
Q

What is recirculation?

A

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

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2
Q

What is the general process of leukocyte movement from blood into tissues?

A

migration/recruitment

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3
Q

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

A

Leukocyte homing

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4
Q

Recruitment of leukocytes and plasma proteins from the blood to the sites of infection and tissue injury is a major part of the process of ____________.

A

inflammation

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5
Q

How is inflammation triggered?

A

recognition of microbes and dead tissues in innate immune responses

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6
Q

Inflammation is refined and prolonged during _______ immune responses.

A

adaptive immune responses

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7
Q

What underlies the trafficking of all subsets of circulating leukocytes?

A

A cascade of adhesive and activation events

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8
Q

Circulating leukocytes tether to and roll on the endothelium through transient interactions of ______ and ______ with their receptors.

A

selections and integrins

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9
Q

What does leukocyte rolling allow?

A

allows leukocytes to sample the endothelium for chemokines

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10
Q

What do chemokines do?

A

-activate integrins -trigger adhesion to endothelium

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11
Q

Adherent leukocytes migrate across the endothelium into _______________.

A

the extravascular space

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12
Q

Once in the extravascular space, leukocytes can migrate down ______________ towards specific areas.

A

chemokine gradients

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13
Q

5 Steps of Leukocyte Recruitment

A

-Tethering -Rolling -Adhesion triggering -Extravasation -Chemotaxis

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14
Q

What constantly circulate through the blood, into the tissues, and often back into the blood again?

A

-immune cells -soluble components

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15
Q

Endothelial cells at sites of infection and tissue injury are activated by ________ secreted by ________ and ________ at these sites.

A

-cytokines -resident macrophages -mast cells

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16
Q

What are the consequences of activated endothelial cells at infection/injury sites?

A

Increased adhesiveness of endothelial cells for: -circulating myeloid leukocytes -Ag-activated effector and memory lymphocytes

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17
Q

What is required for leukocyte/lymphocyte homing and recruitment?

A

the temporary adhesion of the leukocyte to the endothelial cells of blood vessels

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18
Q

Homing involves molecules on the surfaces of what?

A

-leukocytes (homing receptors and chemokine receptors) -endothelial cells (chemokines)

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19
Q

What are addressing?

A

a set of several adhesion molecules on the surface of endothelial cells

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20
Q

Addressin function

A

regulate lymphocyte recirculation via HEV

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21
Q

P-selectin Distribution? Ligand?

A

Distribution: -Endothelium activated by histamine or thrombin Ligand: -Sialyl Lewis X on PSGL-1 and glycoproteins -neutrophils -monocytes -T cells

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22
Q

E-selectin Distribution? Ligand?

A

Distribution: -Endothelium activated by cytokines Ligand: -Sialyl Lewis X on glycoproteins -neutrophils -monocytes -T cells

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23
Q

L-selectin Distribution? Ligand?

A

Distribution: -neutrophils -monocytes -T cells -B cells (naive) Ligand: -Sialyl Lewis X/PNAd on: > GlyCAM-1 > CD34 > MadCAM-1 -endothelium (HEV)

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24
Q

What do selectins do endothelial cells express?

A

-P-selectin (CD62P) -E-selectin (CD62E)

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25
E-selectin pathway
1- Infection 2- Tissue macrophages respond to infection 3- Macrophages produce cytokines IL-1 and TNF 4- 1-2 hours 5- E-selectin synthesized and expressed on endothelial cell surface
26
What are the ligands for E-selectin and P-selectin?
complex sialyated carbohydrates related to the Lewis X or Lewis family
27
Where is L-selectin expressed?
-ONLY expressed on leukocytes and lymphocytes -NOT expressed on endothelial cells
28
What is L-selectin expression activated by?
IL-1 and TNF at inflammation sites
29
L-selectin is important for naive T and B lymphocytes for homing into lymph nodes by \_\_\_\_\_\_\_\_\_\_\_\_.
interacting with high endothelial venules (HEV)
30
What are L-selectin ligands expressed on HEV called?
peripheral node addressins (PNAd)
31
Integrin: LFA-1 (Late functional antigen-1) Distribution? Ligand?
[expressed by leukocytes] Distribution: -neutrophils -monocytes -T cells -B cells (naive) Ligand: -ICAM-1 -ICAM-2 -endothelium
32
Integrin: Mac-1 Distribution? Ligand?
Distribution: -neutrophils -monocytes -dendritic cells Ligand: -ICAM-1 -ICAM-2 -endothelium
33
Integrin: VLA-4 (very late antigen-4) Distribution? Ligand?
[expressed by leukocytes] Distribution: -monocytes -T cells Ligand: -VCAM-1 -endothelium
34
Integrin: alpha4 beta7 Distribution? Ligand?
[expressed by leukocytes] Distribution: -monocytes -T cells -B cells (gut homing) Ligand: -VCAM-1 -MadCAM-1 -endothelium in gut -gut associated lymphoid tissues
35
What are integrins?
heterdimeric cell surface proteins
36
What are integrins composed of?
two noncovalently linked polypeptide chains
37
Integrin functions
-mediate adhesion of cells to other cells to to extracellular matrix via various specific ligands -integrate signals
38
What triggers the integrin signals?
Extracellular ligands with cytoskeleton-dependent: -motility -shape change -phagocytic responses
39
How are integrins able to respond to intracellular signals?
by rapidly increasing their affinity for their ligands (integrin activation)
40
Integrin activation occurs in all leukocytes in response to what?
chemokine binding to chemokine receptors
41
When does integrin activation occur in T lymphocytes?
when Ag bonds to TCRs
42
How is integrin activation mediated?
-by chemokine-induced conformational changes in the extracellular domains of the integrins -leads to increased affinity
43
What is "inside-out signaling"?
-a type of chemokine signaling -involved in integrin activation -inside causes something to change on the surface
44
Integrins on blood leukocytes are normally in a _____ affinity state
low
45
Integrin activation steps
1- Rolling of leukocytes 2- Chemokines on endothelial suface bind leukocyte chemokine receptors 3- Chemokine receptor signaling 4- Leukocyte integrins activated 5- Integrin affinity for their ligands increases
46
What are chemokines?
-large family of structurally homologous cytokines - 8-10kD -contain 2 internal disulfide loops
47
Chemokine function
-stimulate leukocyte movement -regulate migration of leukocytes from blood to tissues
48
4 families of chemokines (based on number and location of N-terminal cysteine residues)
1. CC or Beta chemokines * 2 cysteine residues are adjacent 2. CXC or Alpha chemokines * residues separated by one amino acid 3. C chemokines * 1 cysteine 4. CX3C chemokines * 2 cysteines separated by 3 amino acids
49
**Chemokine: CCL1** * Original name? * Chemokine receptor? * Major function?
* Original name? * I-309 * Chemokine receptor? * CCR8 * Major function? * monocyte recruitment * endothelial cell migration
50
**Chemokine: CCL2** * Original name? * Chemokine receptor? * Major function?
**Chemokine: CCL2** * Original name? * MCP-1 * Chemokine receptor? * CCR2 * Major function? * mixed leukocyte recruitment
51
**Chemokine: CCL3** * Original name? * Chemokine receptor? * Major function?
**Chemokine: CCL3** * Original name? * MIP-1a * Chemokine receptor? * CCR1 * CCR5 * Major function? * mixed leukocyte recruitment
52
**Chemokine: CCL4** * Original name? * Chemokine receptor? * Major function?
**Chemokine: CCL4** * Original name? * MIP-1b * Chemokine receptor? * CCR5 * Major function? * Recruitment of: * T cells * dendritic cells * monocytes * natural killer cells * HIC coreceptor
53
**Chemokine: CCL5** * Original name? * Chemokine receptor? * Major function?
**Chemokine: CCL5** * Original name? * RANTES * Chemokine receptor? * CCR1 * CCR3 * CCR5 * Major function? * mixed leukocyte recruitment
54
**Chemokine: CCL11** * Original name? * Chemokine receptor? * Major function?
**Chemokine: CCL 11** * Original name? * Eotaxin * Chemokine receptor? * CCR3 * Major function? * Recruitment of: * Eosinophils * Basophils * Th2
55
**Chemokine: CCL17** * Original name? * Chemokine receptor? * Major function?
**Chemokine: CCL 17** * Original name? * TARC * Chemokine receptor? * CCR4 * Major function? * T cell recruitment
56
**Chemokine: CCL19** * Original name? * Chemokine receptor? * Major function?
**Chemokine: CCL 11** * Original name? * MIP-3b * Chemokine receptor? * CCR7 * Major function? * T cell and dendritic cell migration into parafollicular zones of lymph nodes
57
**Chemokine: CCL20** * Original name? * Chemokine receptor? * Major function?
**Chemokine: CCL20** * Original name? * MIP-3a * Chemokine receptor? * CCR6 * Major function? * Th17 recruitment * DC positioning in tissue
58
**Chemokine: CCL21** * Original name? * Chemokine receptor? * Major function?
**Chemokine: CCL20** * Original name? * SLC * Chemokine receptor? * CCR7 * Major function? * T cell and dendritic cell migration into parafollicular zones of lymph nodes
59
**Chemokine: CCL22** * Original name? * Chemokine receptor? * Major function?
**Chemokine: CCL22** * Original name? * MDC * Chemokine receptor? * CCR4 * Major function? * Recruitment of: * NK cells * T cells
60
**Chemokine: CXCL1** * Original name? * Chemokine receptor? * Major function?
**Chemokine: CXCL1** * Original name? * GROa * Chemokine receptor? * CXCR2 * Major function? * Neutrophil recruitment
61
**Chemokine: CXCL5** * Original name? * Chemokine receptor? * Major function?
**Chemokine: CXCL5** * Original name? * ENA-78 * Chemokine receptor? * CXCR2 * Major function? * Neutrophil recruitment
62
**Chemokine: CXCL8** * Original name? * Chemokine receptor? * Major function?
**Chemokine: CXCL8** * Original name? * IL-8 * Chemokine receptor? * CXCR-1 * CXCR-2 * Major function? * Neutrophil recruitment
63
**Chemokine: CXCL10** * Original name? * Chemokine receptor? * Major function?
**Chemokine: CXCL10** * Original name? * IP-10 * Chemokine receptor? * CXCR3 * CXCR3B * Major function? * Effector T cell recruitment
64
**Chemokine: CXCL11** * Original name? * Chemokine receptor? * Major function?
**Chemokine: CXCL11** * Original name? * I-TAC * Chemokine receptor? * CXCR3 * CXCR7 * Major function? * Effector T cell recruitment
65
**Chemokine: CXCL12** * Original name? * Chemokine receptor? * Major function?
**Chemokine: CXCL12** * Original name? * SDF-1ab * Chemokine receptor? * CXCR4 * Major function? * mixed leukocyte recruitment * HIV coreceptor
66
**Chemokine: CXCL13** * Original name? * Chemokine receptor? * Major function?
**Chemokine: CXCL13** * Original name? * BCA-1 * Chemokine receptor? * CXCR5 * Major function? * B cell migration into follicles * T follicular helper cell migrationinto follicles
67
**Chemokine: CXCL14** * Original name? * Chemokine receptor? * Major function?
**Chemokine: CXCL14** * Original name? * BRAK * Chemokine receptor? * none * Major function? * Monocyte and dendritic cell migration
68
**Chemokine: XCL1** * Original name? * Chemokine receptor? * Major function?
**Chemokine: XCL1** * Original name? * Lymphotactin * Chemokine receptor? * XCR1 * Major function? * Recruitment of: * T cells * Natural killer cells
69
**Chemokine: CX3CL1** * Original name? * Chemokine receptor? * Major function?
**Chemokine: CX3CL1** * Original name? * Fractalkine * Chemokine receptor? * CX3CR1 * Major function? * Recruitment of: * T cells * Natural killer cells * Monocytes * Activation of: * CTL * Natural killer cells
70
How are neutrophils and monocytes recruited into tissue sites of infection or injury?
Without activation
71
How do neutrophils and monocytes enter the tissues?
through _post-capillary venules_ except parenchymal tissues (liver, lungs, kidney) \>\> through _capillaries_
72
Functions of myeliod leukocytes
1. eliminate infectious pathogens 2. clear dead tissues 3. repair the damage
73
Transmigration of Leukocytes
1. Capture (Selectins) 2. Rolling (Selectins) 3. Activation (Chemokines) 4. Arrest (Adhesion molecules) 5. Firm adhesion (Adhesion molecules) 6. Transmigration from blood vessel lumen through endothelial cells
74
What do activated resident macrophages produce?
Cytokines IL-1 and TNF
75
Function of cytokines IL-1 and TNF
induce rapid induction of expression of pre-formed P selectins on the surface of endothelial cells
76
What initiates rolling of leukocytes on the endothelium?
The interaction between P-selectins and ligands on the leukocytes
77
How is rolling of leukocytes stabilized?
By L-selectin binding to ligands on the endothelial cells
78
What chemokine does endothelial cells present that is then recognized by receptors on neutrophils?
CXC-chemokine ligand 8 CXCL8 or IL-8
79
Which cytokine controls the transmigration of monocytes?
CCL2 or MCP-1
80
What happens after leukocytes have completed trans-endothelial migration?
they interact with cytokines in the underlying basement membrane
81
What happens to leukocytes after diapedesis?
* the cells adopt an amoeboid shape * migrate in polarized fashion along collagen fibrils in response to chemotactic gradient toward site of infection/inflammation
82
On which edge are the chemotactic receptors located?
the leading edge
83
Naive T cell migration/recirculation pathway
1. Naive T cells leave blood preferentially 2. Enter lymph nodes across the HEVs 3. DCs with Ag enter lymph nodes through lymphatic vessels 4. T cells activated if they recognize the Ag 5. Return to arterial ciruclation
84
Effector and Memory T cell migration/recirculation pathway
1. Effector and memory T cells leave blood preferentially 2. Enter peripheral tissues through venules at sites of inflammation
85
By which lymphocytes is L-selectin expressed?
By both T and B lymphocytes
86
How was the biological importance of L-selectin demonstrated?
Experiments showing that L-selectin deficient lymphocytes are: **unable to enter peripheral nodes and "see" the Ag**
87
What are L-selectin ligands expressed on HEVs called?
PNAd peripheral node addressins
88
Naive T lymphocytes home to lymph nodes as a result of \_\_\_\_\_\_\_\_.
L-selectin binding to peripheral lymph node addressin (PNAd) on HEV
89
HEVs are ONLY present on which organs?
secondary lymphoid organs
90
Which cytokines are displayed on the surface of the HEV?
CCL19 and CCL21
91
Why do naive T cells have low levels of SIPR1?
because the receptor is internalized after binding S1P in the blood
92
S1PR1
Sphingosine-1-phosphate receptor 1
93
What happens to the naive T cells that have recently entered a lymph node?
* they _cannot sense S1P concentration gradient_ between the T cell zone of the node and the lymph * they _cannot exit the node for several hours_ until S1PR1 is re-expressed
94
Where do activated effector T cells home to?
sites of infection in peripheral tissues
95
How is effector T cell migration into peripheral tissue mediated?
mediated by _E-selectins, P-selectins, integrins, and CXCL10_ which are produced at the sites of infection
96
What is CD44 important for?
Important for the mobilization of effector T cells in sites of infection or inflammation
97
What is secreted and expressed by endothelial cells at the site of infection or inflammation?
* Secreted = chemokines * Expressed = * E-selectins * P-selectins * Hyaluronic acid (HA)
98
What can mediate rolling interactions with vascular endothelial cells that express HA or even E-selectins?
CD44
99
Chemokine signaling via GPCRs results in \_\_\_\_\_\_.
* Increased integrin affinity (such as VLA-4) * Which enhances adhesiveness (inside-out signaling)
100
Engagement of CD44 with HA may also trigger what?
GPCR-dependent "inside-out" upregulation of VLA-4-VCAM binding
101
What mechanism do naive B cells use to home to secondary lymphoid tissues throughout the body?
use the same basic mechanisms as do naive T cells
102
What is the pathway of immature B cells once they leave the bone marrow?
1. Leave bone marrow through blood 2. Enter red pulp of spleen 3. Migrate to the periphery of the white pulp
103
What chemokine receptor do B cells express as they mature further?
CXCR5
104
What does CXCR5 do?
promotes movement of B cells into the white pulp of spleen in response to CSCL13
105
What happens once B cell maturation is completed within the white pulp of the spleen?
1. Mature naive B cells reenter the circulation 2. Home to lymph nodes and mucosal lymphoid tissues
106
What is required for the homing process of mature naive B cells?
* cytokines CXCL12 and CCL19/CCL21 on HEV * their chemokine receptors CXCR4 and CCR7 on naive B cells
107
What drives the B cell migration into follicles in the stroma?
CXCL13 recognized by CXCR5 which is expressed on naive B cells
108
How can the B cells in follicles become activated?
B cells may encounter Ag to become activated
109

IMMUNOLOGY Exam #1- Lo (6 decks)

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