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Immunology Tutors Review > Leukocyte Migration- Lecture 3 > Flashcards

Leukocyte Migration- Lecture 3 Flashcards

1
Q

What is the definition of Migration/Recruitment/Leukocyte homing?

A

Leukocytes from blood Tissue (used to fight and respond to infection)

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2
Q

What is the definition of recirculation?

A

LYMPHOCYTES moving from blood back to secondary lymph tissue (naïve) in order to look for antigen

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3
Q

What are chemokines?

A

Types of cytokines that regulate movement of leukocytes

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4
Q

How do families of chemokines differ?

A

Because of the number and location of N-terminal Cysteine residues

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5
Q

What is the role of chemokine CCL2/MCP-1?

A

Monocyte recruitment

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6
Q

What is the role of chemokine CCL19/MIP-3ß?

A

T cell/Dendritic Cell migration into LN

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7
Q

What is the role of chemokine CCL21/SLC?

A

T cell migration into LN

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8
Q

What is the role of chemokine CXCL8?***

AKA IL-8

A

Neutrophil recruitment

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9
Q

What is the role of chemokine CXCL10?

A

Effector T cell recruitment

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10
Q

what is the role of chemokine CXCL12?

A

Naive B cells to LN (homing)

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11
Q

What is the role of chemokine CXCL13?

A

B cell migration to follicles

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12
Q

What are the 6 steps of leukocyte migration?

A
  1. Infection/Inflammation
  2. Activation of Endothelium
  3. Tethering (Selectins)
  4. Rolling (Integrins/Inside-out signaling)
  5. Adhesion and stop
  6. Transmigration into tissue
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13
Q

Neutrophils/monocytes start in _____ and can enter and circulate through the blood

A

Bone marrow

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14
Q

Do Neutrophils need to be activated to leave bone marrow and enter blood circulation

A

No they do not

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15
Q

When do neutrophils enter the tissues and how do they enter?

A

When infection/inflammation is detected

Neutrophils leave the blood and enter tissues through POST CAPILLARY VENULES

In liver, lungs, and kidney they enter via capillaries

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16
Q

Neutrophils and monocytes are activated by _______ or _______

A

Pathogen

Inflammation

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17
Q

Once neutrophils are activated, what do they produce and why?

A

Neutrophils produce IL-1 to recruit other leukocytes/lymphocytes

18
Q

During the second stage of leukocyte migration, healthy tissues that originally do not have selectins present on the epithelium begin to express selectins. Why?

A

Cytokines released during infection/inflammation activate the expression of selectins on endothelium.

*Note that selectins can also be found on leukocytes/lymphocytes, but they are not activated by cytokines.

19
Q

What are the 3 selectins and where are they found?

A

P-selectin –> On endothelium
E-selectin –> On endothelium

L-selectin –> On leukocytes/lymphocytes

20
Q

What activates P-selectin?

A

Activated by Histamine/thrombin`

21
Q

What activates E-selectin?

A

TNF and IL-1

22
Q

What do E-selectin and P-selectin bind to once activated?

A

Xialyl Lewis X on lymphocytes/leukocytes

23
Q

What activates L-selectin and what does it bind to?

A

L-selectin is not activated by anything, therefore it is always active

Binds to PNAD (peripheral node addressins) on HEV on endthelium

24
Q

What is the purpose of step 3 of leukocyte migration, tethering of the selectins?

A

NECESSARY to slow down leukocytes to initiate rolling

25
Q

What carries out step 4 of leukocyte migration, rolling?

A

Integrins by mediating adhesion of leukocytes to the endothelium

26
Q

Where are integrins found?

A

On leukocytes and they bind to the endothelium

27
Q

What are the ligands that these integrins bind to? (remember that the integrins are found on leukocytes, so their ligands will be found on the endothelium)

LFA1?
MAC1?
VLA4?
A4ß7?

A

LFA1: ICAM
MAC1: ICAM
VLA4: VCAM1
A4ß7: VCAM1 and MadCAM1 (Molecular Addressin Cell Adhesion Molecule)

28
Q

Integrins on leukocytes in blood without chemokines= _____

A

Weak affinity

29
Q

Integrins on leukocytes in blood with chemokines= _______. Why?

A

High affinity

*due to chemokines from the injured/infected site of endothelium

30
Q

NAIVE CELLS= __ _____ _____= __ _____

A

NAIVE CELLS= NO CHEMOKINE RECEPTORS= NO ROLLING

31
Q

ACTIVATED CELLS will have _____ ______

A

Chemokine receptors

32
Q

Integrins bind to ligands on_____ with high affinity

A

Endothelium

33
Q

When integrins bind to the ligands what happens?

A

Stops leukocytes from rolling

34
Q

In what way is T cell migration in tissues different from leukocytes?

A

Rolling is mediated by hyaluronic acid on T cell binding to CD44 on the endothelium. When these bind, VLA4/VCAM integrin binding increases and EFFECTOR T cells mobilize.

35
Q

What is another name for transmigration into tissues?

A

Diapedesis

36
Q

What occurs during the 6th stage of leukocyte migration “diapedesis/transmigration into tissues”?

A

Cells slide through gap junctions and openings between endothelial cells to leave the blood and enter the tissue with an “amoeboid” shape.

Leukocytes then migrate towards site of infection based on more chemokines being released by cells already at infection site.

37
Q

Explain what happens during migration of naive B cells and lymphocytes.

A

Enter LN via HEV
Have L-Selectins on them
-Bind to PNADS on HEV
-CCR7 (on T cells) bind to CCL19/21 (HEV) to activate integrins on HEV

38
Q

Explain what happens during recirculation of B cells and lymphocytes when antigens are not found and when they are found.

A

No Ag is found –> B and T cells returns to lymph (efferent lymph vessel) and enters other secondary lymph organs –> eventually reaches thoracic duct and is returned to IVC

Ag is found and B/T cell is activated –> B/T cell returns to circulation. Goes through tethering/rolling/adhesion process until it enters tissue where Ag came from. *Note that T cells bind to CXCL10.

39
Q

Where do B and T cells enter LN’s?

A

HEV

40
Q

How are B and T cells separated in the lymph node?

A

CXCR5 (on B cells) binds to CXCL13 (secreted from primary follicle). In spleen enter the red pulp and migrate to where CXCL13 Is secreted from (white pulp). Immature to mature and then reentry into circulation.
*Note that in primary follicles B cells can find their antigen and proliferate to form secondary follicles

CCR7 (on T cell) binds to CCL21 in T cell zone

41
Q

Explain the pathway of the T cell from entry to exit of the LN in terms of S1P.

A

In the blood S1P (a blood homing protein) binds to S1PR1 (receptor on T cells), which allows for T cell entry into the LN.

Binding causes internalization of S1PR1, which means S1P can no longer be sensed.

Reexpression of S1PR1 allows S1P to bind, leading to the T cell exiting the LN.

Immunology Tutors Review (9 decks)

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