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Exam 1 > 02/16e Immune Cell Migration > Flashcards

02/16e Immune Cell Migration Flashcards

1
Q

What are the four steps of leukocyte extravasation?

A

1) Slow down and contact the endothelium (tether)
2) Stop signal (trigger)
3) Stop (stick)
4) Guide into tissue/extravasation (carrot)

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2
Q

What are the molecular mediators of extravasation?

A

Selectins - glycoproteins that mediate slowing down
Chemokines - endogenous mediators of cell migration, generate the stop signal
Integrins - cause stopping by mediating firm adhesion
Chemokines and other chemotactic factors - guide leukocytes into the tissue

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3
Q

What are selectins?

A

Adhesion molecules that mediate an initial step of low-affinity adhesion between leukocytes and endothelial cells
Bind carbohydrate structures (low-affinity)
Slow rapidly-moving leukocytes enough to cause them to roll across the endothelial surface

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4
Q

What are the three types of selectins? Where are they expressed, and what activates them?

A

P-selectin - expressed on endothelium and activated by cytokines, histamine, or thrombin
E-selectin - expressed on endothelium and activated by cytokines and LPS
L-selectin - expressed on neutrophils, monocytes, and naive T and B cells

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5
Q

What are the ligands for selectins?

A

Glycoproteins that are expressed at the tips of cellular microvilli

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6
Q

What are integrins?

A

Heterodimeric cell surface proteins that mediate adhesion of cells to other cells or to extracellular matrix
Consist of extracellular globular heads that interact with ligands outside the cell, and cytoplasmic domains that interact with cytoskeletal proteins
Activated into their high affinity state by chemokines

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7
Q

What are CAMs?

A

Cellular Adhesion Molecules - ligands for integrins

Expressed on cytokine-activated leukocytes and endothelial cells

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8
Q

What are four important leukocyte integrins?

A

LFA-1 - expressed on neutrophils, monocytes, and T cells; bind to ICAM-1 and ICAM-2 on endothelial cells
Mac-1 - expressed on monocytes and dendritic cells; bind to ICAM-1 and ICAM-2
VLA-4 - expressed on monocytes and T cells; bind to VCAM-1 on endothelial cells
alpha4beta7 - expressed on monocytes and T cells; bind to MadCAM-1 on endothelium in the gut

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9
Q

What are the functions of integrin-CAM interactions?

A

Mediate FIRM adhesion of leukocytes to endothelium, of immune cells to each other, and of cells to extracellular matrix proteins
Mediate leukocyte rolling in cases of high inflammation

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10
Q

What are chemokines?

A

Chemotactic cytokines
Have a highly conserved amino acid domain, with four conserved cysteines
Act as mediators of inflammation and constitutive leukocyte migrations (tell WBCs where to go!)
Bind to G-protein coupled receptors

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11
Q

What accounts for the migration specificity of different types of leukocytes?

A

Different combinations of chemokine receptors are expressed on different types of leukocytes
Some receptors are activated by many different cytokines (usually mediate inflammation), others are more selective

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12
Q

What are the two major functions of chemokines?

A

Stimulate directional migration of leukocytes

Activate integrins

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13
Q

What are inflammatory chemokines? What do they do?

A

Chemokines that are turned on by infection or insult, and stimulate inflammation
Not expressed in normal tissues
Regulated through chemokine expression

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14
Q

What are two major inflammatory chemokines, and what are their targets?

A

IL-8 (CXCL8) - targets neutrophils

MCP-1 (CCL2) - targets monocytes and memory T cells

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15
Q

What are lymphoid chemokines? What do they do?

A

Chemokines that are constitutively expressed in lymphoid organs
Mediate lymphocyte recirculation
Act in lymphoid tissue development and maintain lymphoid structures
Regulated through receptor expression

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16
Q

What are two major lymphoid chemokines, and what are their targets?

A

CCL21 (SLC) - target naive T cells and activated dendritic cells
CXCL13 (BLC) - target B cells

17
Q

What is fMLP?

A

Formylmethionyl-leucyl-phenylalanine, a formyl peptide
Chemotactic factor released from bacteria in vivo or after decomposition, that activates specific GPCRs on neutrophils and monocytes

18
Q

What are three other examples of molecules with chemotactic activity?

A

fMLP
Products of the complement cascade
Leukotrienes

19
Q

What are the four steps to initiating innate cell migration?

A

1) Pathogens produce chemotactic factors
2) Pathogen-associated molecular patterns (PAMPs) and cytokines activate stromal and endothelial cells
3) Activated stromal cells produce inflammatory chemokines
4) Activated endothelial cells produce chemokines and increase expression of selectins and CAMs

20
Q

What five events are included in adaptive cell migration?

A

1) Constitutie naive lymphocyte migration
2) Migration of activated dendritic cells
3) Cellular migration within secondary lymphoid organs
4) Egress from secondary lymphoid organs
5) Migration of effector lymphocytes to target tissues

21
Q

What is Leukocyte Adhesion Deficiency Type 1?

A

Autosomal recessive disorder characterized by a lack of integrins
Causes a lack of neutrophil accumulation at site of infection and defects in adherence-dependent functions
Results in recurrent bacterial and fungal infections

22
Q

What is Leukocyte Adhesion Deficiency Type 2?

A

Genetic lack of enzymes needed to express ligands for selectins on neutrophils
Causes a lack of neutrophil accumulation at sites of infection
Results in recurrent bacterial and fungal infections

23
Q

What chemokine stimulates the migration of neutrophils?

A

IL-8 (CXCL8)

24
Q

What chemokine stimulates the migration of monocytes and memory T cells?

A

MCP-1 (CCL2)

25
Q

What chemokine stimulates the migration of naive T cells and activated dendritic cells into lymphoid organs?

A

SLC (CCL21)

26
Q

What chemokine stimulates the migration of B cells in lymphoid follicles?

A

BLC (CXCL13)

27
Q

Which selectins are expressed on endothelium?

A

P-selectin and E-selectin

28
Q

What selectin is expressed on leukocytes (neutrophils, monocytes, naive T and B cells)?

A

L-selectin

29
Q

What integrin is expressed on neutrophils, monocytes, and T cells?

A

LFA-1

30
Q

What integrin is expressed on monocytes and dendritic cells?

A

Mac-1

Exam 1 (15 decks)

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