Lecture 3: Leukocyte Circulating and Migration into Tissue

Question 1

Migration/recruitment definition

Answer 1

General process of leukocyte movement from blood into tissues

Question 2

Recirculation

Answer 2

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

Question 3

Leukocyte homing

Answer 3

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

Question 4

Major part of process of inflammation

Answer 4

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

Question 5

Inflammation triggered by

Answer 5

Recognition of microbes and dead tissues

Question 6

Steps of adhesion events

Answer 6

Tethering
Rolling
Adhesion and stop
Transmigration into tissue

Question 7

Tethering

Answer 7

Occurs through transient interaction of selectins and integrins with their ligands

Question 8

Rolling

Answer 8

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

Question 9

What triggers leukocyte adhesion to endothelium

Answer 9

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

Question 10

Trasmigration

Answer 10

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

Question 11

What causes expression of adhesion molecules on endothelial cells

Answer 11

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

Question 12

Consequence of expression of adhesion molecules on endothelial cells

Answer 12

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

Question 13

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

Answer 13

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

Question 14

What are Addressins

Answer 14

A set of adhesion molecules on the surface of HEVs

Question 15

Selectin affinity is high or low with their ligands

Answer 15

Selectins have low affinity interaction with their ligands

Question 16

Activated endothelial cells express what selectins

Answer 16

P-selectin and E-selectin

Question 17

E-selectin expressed on

Answer 17

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

Question 18

Expression of ligands for P selectin and E selectin

Answer 18

Ligands are constitutively expressed

Question 19

L-selectin expressed on

Answer 19

Expressed on leukocytes/lymphocytes.

Question 20

Importance of L-selectin

Answer 20

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

Question 21

L-selectin ligand expressed on HEV is called

Answer 21

Peripheral node addressins (PNAds)

Question 22

P-selectin expressed on

Answer 22

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

Question 23

P-selectin and E- selectin ligand

Answer 23

Sialyl Lewis X

Question 24

Integrin affinity with ligand

Answer 24

High affinity to ligand

Question 25

All leukocytes express

Answer 25

Lymphocyte function associated antigen I | LFA-1

Question 26

LFA-1 ligand name and where its expressed

Answer 26

ICAM-1 on cytokine-activated endothelial cells

Question 27

VLA-4 expressed where and binds to what

Answer 27

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

Question 28

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

Answer 28

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

Question 29

Mac-1 expressed where binds what

Answer 29

Neutrophils/monocytes/Dendritic cells | ICAM-1, ICAM-2

Question 30

What activates integrins and what is the result | What type of signaling is this

Answer 30

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

Question 31

Family/size of chemokine

Answer 31

Large family of cytokines 8-10kD

Question 32

Chemokine function

Answer 32

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

Question 33

C vs Beta Vs Alpha vs CX3C chemokines

Answer 33

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

Question 34

What do neutrophils/monocytes enter tissue through

Answer 34

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

Question 35

Neutrophils recognize what ligand on endothelial cells

Answer 35

CXCL8 aka IL-8

Question 36

Monocytes recognize what ligand on endothelial cells

Answer 36

CCL2 aka MCP-1

Question 37

Leukocyte migration following diapedesis/transmigration

Answer 37

They adopt amoeboid shape | Migrate in polarized fashion along collagen fibers in response to chemotactic gradient

Question 38

Naive T-cells inter lymph node through

Answer 38

HEVs

Question 39

Dendritic cells with Ag enter lymph node through

Answer 39

lymphatic vessels

Question 40

What happens when T-cell recognize Ag in lymph node

Answer 40

They are activated and return to circulation

Question 41

What is the result of an L-selectin deficient lymphocyte

Answer 41

They are unable to enter peripheral nodes and "see" the antigen

Question 42

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

Answer 42

Leaves LN via efferent lymphatics and travels downstream

Question 43

HEVs are present where

Answer 43

ONLY in SECONDARY lymph organs

Question 44

What chemokines are on the surface of HEVs

Answer 44

CCL19 and CCL21

Question 45

Naive T-cell S1PR1 expression and result

Answer 45

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

Question 46

Activated T-cell S1PR1 expression and result

Answer 46

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.

Question 47

CD44 importance

Answer 47

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

Question 48

Immature Naive B cell migration and maturation

Answer 48

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

Question 49

B cells may be activated where

Answer 49

In lymph node follicles