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Immunology > Lecture 3: Leukocyte Circulating and Migration into Tissue > Flashcards

Lecture 3: Leukocyte Circulating and Migration into Tissue Flashcards

1
Q

Migration/recruitment definition

A

General process of leukocyte movement from blood into tissues

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2
Q

Recirculation

A

Ability of lymphocytes to repeatedly ‘home’ to SECONDARY lymphoid organs, reside there transiently, and return to the blood

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3
Q

Leukocyte homing

A

Cell migration out of the blood and into PERIPHERAL TISSUES, or to a site of infection/injury

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4
Q

Major part of process of inflammation

A

Recruitment of leukocytes and plasma proteins to sites of infection/injury

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5
Q

Inflammation triggered by

A

Recognition of microbes and dead tissues

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6
Q

Steps of adhesion events

A

Tethering
Rolling
Adhesion and stop
Transmigration into tissue

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7
Q

Tethering

A

Occurs through transient interaction of selectins and integrins with their ligands

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8
Q

Rolling

A

Allows chemokine receptors on leukocytes to bind chemokines expressed on endothelium
Initiated by P-selectin and their ligands

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9
Q

What triggers leukocyte adhesion to endothelium

A

Receptors signal and activate integrins on leukocytes which interact with ligands on endothelium

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10
Q

Trasmigration

A

After adhesion, leukocytes transmigrate into extravascular space and migrate down chemokine gradients

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11
Q

What causes expression of adhesion molecules on endothelial cells

A

Endothelial cells are activated at sites of infection/injury by cytokines secreted from resident immune cells

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12
Q

Consequence of expression of adhesion molecules on endothelial cells

A

Increased adhesion of myeloid leukocytes and Ag-activated and memory leukocytes, NOT naive luekocytes

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13
Q

T or F: Homing involves molecules on the surfaces of both the leukocytes and endothelial cells

A

True.
Leukocytes- homing receptors and chemokine receptors
Endothelial cells- chemokines

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14
Q

What are Addressins

A

A set of adhesion molecules on the surface of HEVs

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15
Q

Selectin affinity is high or low with their ligands

A

Selectins have low affinity interaction with their ligands

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16
Q

Activated endothelial cells express what selectins

A

P-selectin and E-selectin

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17
Q

E-selectin expressed on

A

Expressed on endothelial cells activated by cytokines (TNF, IL-1) within 1-2 hours

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18
Q

Expression of ligands for P selectin and E selectin

A

Ligands are constitutively expressed

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19
Q

L-selectin expressed on

A

Expressed on leukocytes/lymphocytes.

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20
Q

Importance of L-selectin

A

Used by Naive T and B lymphocytes for homing into lymph nodes by interacting with HEVs
Further stabilizes rolling

21
Q

L-selectin ligand expressed on HEV is called

A

Peripheral node addressins (PNAds)

22
Q

P-selectin expressed on

A

Endothelial cells activated by histamine/thrombin or TNF or IL-1

23
Q

P-selectin and E- selectin ligand

A

Sialyl Lewis X

24
Q

Integrin affinity with ligand

A

High affinity to ligand

25
Q

All leukocytes express

A

Lymphocyte function associated antigen I

LFA-1

26
Q

LFA-1 ligand name and where its expressed

A

ICAM-1 on cytokine-activated endothelial cells

27
Q

VLA-4 expressed where and binds to what

A

Expressed on leukocytes, binds to VCAM-1 on activated endothelial cells

28
Q

alpha(4)beta(7)integrin expressed where binds what

A

Expressed on leukocytes, binds to VCAM-1 and MadCAM on endothelial cells

29
Q

Mac-1 expressed where binds what

A

Neutrophils/monocytes/Dendritic cells

ICAM-1, ICAM-2

30
Q

What activates integrins and what is the result

What type of signaling is this

A

Chemokines binding to chemokine receptors, causing conformation change in integrin
Result is increase in integrin affinity to ligand
Inside-out signaling

31
Q

Family/size of chemokine

A

Large family of cytokines 8-10kD

32
Q

Chemokine function

A

Stimulate leukocyte movement and regulate migration of leukocytes from blood to tissues

33
Q

C vs Beta Vs Alpha vs CX3C chemokines

A

C- single cysteine
Beta- two cysteines
Alpha- two cysteines separated by one AA
CX3C- two cysteines separated by three AAs

34
Q

What do neutrophils/monocytes enter tissue through

A

Post-capillary venules, except in parenchymal tissues (liver, lung, kidney) where all blood enters through capillaries

35
Q

Neutrophils recognize what ligand on endothelial cells

A

CXCL8 aka IL-8

36
Q

Monocytes recognize what ligand on endothelial cells

A

CCL2 aka MCP-1

37
Q

Leukocyte migration following diapedesis/transmigration

A

They adopt amoeboid shape

Migrate in polarized fashion along collagen fibers in response to chemotactic gradient

38
Q

Naive T-cells inter lymph node through

A

HEVs

39
Q

Dendritic cells with Ag enter lymph node through

A

lymphatic vessels

40
Q

What happens when T-cell recognize Ag in lymph node

A

They are activated and return to circulation

41
Q

What is the result of an L-selectin deficient lymphocyte

A

They are unable to enter peripheral nodes and “see” the antigen

42
Q

If a lymphocyte does not find an Ag in the lymph node, what happens

A

Leaves LN via efferent lymphatics and travels downstream

43
Q

HEVs are present where

A

ONLY in SECONDARY lymph organs

44
Q

What chemokines are on the surface of HEVs

A

CCL19 and CCL21

45
Q

Naive T-cell S1PR1 expression and result

A

Naive T-cells have low S1PR1 expression. They cannot exit node for several HOURS until expression increases and they can detect S1P gradient

46
Q

Activated T-cell S1PR1 expression and result

A

T-cells that recently entered LN and are activated still have low S1PR1 expression. It takes several days to re-express S1PR1 and allow exit from node.

47
Q

CD44 importance

A

Important for mobilization of effector T cells in sites of infection
Can mediate rolling interactions with endothelial cells expressing Hyaluronic acid or E-selectin

48
Q

Immature Naive B cell migration and maturation

A

Migrate from bone marrow, through the blood, enter red pulp then migrate to white pulp
After maturing in white pulp, they home to secondary lymph organs

49
Q

B cells may be activated where

A

In lymph node follicles

Immunology (21 decks)

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