Lecture 5: Inflammation and Leukocyte Migration Flashcards by Alexa Crawford | Brainscape

Q

what causes the inflammatory response in general?

A

local injury or tissue trauma

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

what 4 physical things characterize the inflammatory response?

A

redness (rubor)
heat (calor)
swelling (tumor)
pain (dolor)

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

t/f the inflammatory response involves various leukocytes, and soluble and membrane-bound molecules

A

t

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

in the inflammatory response, CAMs are crucial for _____ interactions during inflammation

A

leukocyte-tissue

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

CAMs include _____ (4)

A

selectins
mucins
integrins
immunoglobulin-superfamily CAMs

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

tissue damage and bacteria cause resident sentinel cells to release ___ and ____ to trigger a local increase in ____ and ___

A

chemotractants and vasoactive factors; blood flow and capillary permeability

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

when neutrophils and phagocytes migrate to the site of inflammation, this is called _____

A

chemotaxis

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

what 2 molecules are involved in neutrophil rolling?

A

L-selectin and PSGL-1

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

what 2 molecules are involved in neutrophil rolling?

A

L-selectin and PSGL-1

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

what 2 molecules are involved in neutrophil rolling?

A

L-selectin and PSGL-1

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

what chemokines are involved in neutrophil activation?

A

IL-8 and macrophage inflammatory protein 1b (MIP-1b (akaCCL4))

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

what chemokines are involved in neutrophil activation?

A

IL-8 and macrophage inflammatory protein 1b (MIP-1b (akaCCL4))

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

what chemokines are involved in neutrophil activation?

A

IL-8 and macrophage inflammatory protein 1b (MIP-1b (akaCCL4))

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

what chemokines are involved in neutrophil activation?

A

IL-8 and macrophage inflammatory protein 1b (MIP-1b (akaCCL4))

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

what chemokines are involved in neutrophil activation?

A

IL-8 and macrophage inflammatory protein 1b (MIP-1b (akaCCL4))

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

what molcules are involved in neutrophil adhesion?

A

LFA-1 and MAC-1

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

what immune cells are typically the first to the site of inflammation?

A

neutrophils

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

what do neutrophils respond to?

A

C5a
bacterial peptides containing N-formyl peptides
leukotrienes in inflammed tissues

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

what molecule is involved in rolling inflammatory monocytes?

A

L-selectin

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

what chemokines are involved with activation of inflammatory monocytes?

A

monocyte-chemotractant protein-1 (MCP-1, CCL-2)

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

what is the molecule involved with adhesion of inflammatory monocytes?

A

VLA-4

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

what molecules are involved in rolling naive lymphocytes?

A

L-selectin, LFA-1, VLA-4

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

what chemokines are involved in activation of naive lymphocytes?

A

CCL21, CCL19 and CXCL12 (for T cells) and CXCL13 (for B cells)

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

what molecules are involved in naive lymphocyte adhesion?

A

LFA-1 and VLA-4

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

naive lymphocytes travel across ____ to enter the lymph node

A

high-endothelial venules

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

give 3 examples of selectins

A

L, E, and P selectins

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

what are selectins?

A

glycoproteins that bind specific carbohydrate groups

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

give and example of a specific carb group selectins bind to and how they bind

A

sialyl-Lewis x via a lectin-like domain

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

what are mucins?

A

glycosylated proteins that present sialyl-Lewisx and other carb groups to selectins

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

what are integrins?

A

cell surface heterodimeric proteins that bind extracellular matric molecules (like fibronectin) and ICAMs

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

what are ICAMs?

A

immunoglobulin-superfamily glycoproteins that bind integrins

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

give an example of a mucin-like CAM

A

CD34

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

give 3 examples of Ig-superfamily CAMs

A

ICAM-1,-2,-3
VCAM-1
MAdCAM-1

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

MAdCAM-1 has both ___ and ___ like properties

A

mucin-like and ig-superfamily

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

give 3 examples of integrins

A

a4B1 (VLA-4, LPAM-2)
aLB2 (LFA-1)
aMB2 (CR4, p150/95)

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

chemokines control what 3 leukocyte functions?

A

adhesion
chemotaxis
actvation

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

chemokines are ___ expressed and are also produced in response to ___

A

constitutively; inflammation

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

most chemokines belong to ____ or ___ subgroups

A

CC or CXC

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

what is the structure of chemokine receptors?

A

7-membrane spanning proteins that signal through hetrodimeric G proteins

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

t/f individual chemokine receptors are able to bind more than one chemokine

A

t

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

chemokine receptor expression is limited to certain cell types to confer ___

A

specificity to the action of given chemokines

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

what are the CXC subgroups of the CXCR1 chemokine receptors?

A

IL-8 (CXCL 8) and GCP-2 (CXCL 6)

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

what are the CXC subgroups of the CXCR2 chemokine receptor?

A

IL-8 (CXCL 8), Gro-a (CXCL 1), Gro-B (CXCL 2), gro-y (CXCL 3), NAP-2 (CXCL 7) and ENA-78 (CXCL5)

How well did you know this?

1

Not at all

2

3

4

5

Perfectly

Q

what are the CXC subgroups of the CXCR4 (CXCL11) chemokine receptor?

A

SDF-1 (CXCL12)

Q

give an example of a chemokine that binds to the CCR1 chemokine receptor

A

RANTES (CCL5)

Q

give an example of a chemokine that binds to the CCR2 chemokine receptor

A

MCP-1 (CCL2)

Q

give an example of a chemokine that binds to the CCR3 chemokine receptor

A

RANTES (CCL5)

Q

____ and ____ mediate the migration of leukocytes across the endothelial cell layer of blood vessels

A

chemotractants and CAM interactions

Q

blood-borne neutrophils and monocytes enter sites of inflammation by a process called ___

A

extravasation

Q

cytokines and other products of inflammation cause endothelial cells to increase ____ expression

A

CAM

Q

neutrophil rolling is promoted by _____ interactions

A

selectin-mucin

Q

chemokines such as ___ activate neutrophils

A

IL-8

Q

integrins on activated neutrophils assume a ____ conformation that allows neutrophil arrest and adhesion to ____

A

high affinity; immunoglobulin-superfamily CAMs

Q

selectins are important in what phase of neutrophil rolling and extravasation?

A

rolling

Q

during neutrophil extravasation, chemokines induce ____ change of neutrophils and clustering of ___

A

conformational; integrins

Q

during neutrophil extravasation, chemokines induce ____ change of neutrophils and clustering of ___

A

conformational; integrins

Q

recirculation of lymphocytes from blood to bone marrow, spleen, lymph nodes and tertiary extralymphoid tissues occurs at least once every ____

A

24 hours

Q

what is the point of lymphocyte recirculation?

A

ensures that the greatest number of antigen-specific lymphocytes have the opportunity to encounter and interact with antigen in lymphoid tissues

Q

migration of lymphocytes into lymph nodes takes place across ____

A

high endothelial venules

Q

lymphocyte rolling during lymphocyte extravasation is promoted by ____

A

weak interactions between lymphocyte L-selectin and endotheial cell mucin

Q

what is the role of chemokines constitutively expressed by endothelial cells in lymphocyte extravasation?

A

activate lymphocytes, causing integrins to assume a high affinity conformation

Q

what is the role of integrins in lymphocyte extravasation?

A

mediate lymphocyte arrest and adhesion to immunoglobulin-superfamily CAMs

Q

transendothelial migration of lymphocytes is mediated by ___ molecules

A

junctional adhesion

Q

what is the function of homing receptors on lymphocytes?

A

recognoze specific CAMs to mediate the differential migration of lymphocyte subsets into different tissues

Q

give 2 examples of chemokines involved in lymphocyte homing and trafficking and their role

A

MIP-1B (attracts naive T cells)

2. RANTES (attracts memory T cells)

Q

naive lymphocytes do not have ____ homing, so they are trafficked to ___

A

tissue-specific; secondary lymphoid tissues

Q

effector lymphocytes traffic to sites of ___

A

inflammation

Q

effector lymphocytes traffic to sites of ___

A

inflammation

Q

where do memory lymphocytes home to ?

A

the tissue type where a specific antigen was first encountered

Q

what are 3 important lipid mediators of inflammation? What produces them?

A

thromboxane
prostaglandins
leukotrienes
tissue mast cell and macrophages

Q

what is the function of thromboxane?

A

vasoconstriction and platelet aggregation

Q

what are the functions of prostaglandins?

A

increase vascular permeability, vascular dilation and neutrophil chemotaxis

Q

what are the functions of leukotrienes C4, D4, and E4?

A

mediate lung inflammation

Q

what is the function of leukotriene B4?

A

causes neutrophil chemotaxis

Q

what are the functions of platelet activation factor (a lipid mediator of inflammation)

A

platelet aggregation, neutrophil activation, and eosinophil chemotaxis

Q

chemokines, anaphylatoxins, proinflammatory cytokines and interferon-y are all ___

A

mediators of inflammation

Q

what are the functions of chemokines as mediators of inflammation?

A

attract leukocyte subsets to sites of inflammation

2. regulate the expression and conformation of CAMs

Q

what are the functions of anaphylatoxins (C3a and C5a) as inflammatory mediators?

A

trigger tissue mast cell release of histamine, leading to contraction of smooth mucle and increased vascular permeability

Q

what are the functions of proinflammatory mediators TNF-a, IL-1 and IL-6?

A

have multiple redundant effects including fever, acute phase protein synthesis, increased CAM expression and increased vascular permeability during acute inflammation

Q

what are the functions of IFN-y and TNF-a as inflammatory mediators?

A

important in chronic inflammation and can cause tissue damage

Q

is IL-1 pyrogenic?

A

yes

Q

is TNF-a pyrogenic?

A

yes

Q

is IL-6 pyrogenic?

A

yes

Q

can IL-1 trigger synthesis of acute phase proteins by teh liver?

A

yes

Q

can TNF-a trigger synthesis of acute phase proteins by the liver

A

yes

Q

can IL-6 trigger synthesis of acute phase proteins by teh liver?

A

yes

Q

of IL-1, TNFa and IL-6, which can increase vascular permeability?

A

all

Q

of IL-1, TNFa, and IL-6, which can cause increased adhesion molecules on vascular endothelium?

A

all EXCEPT IL-6

Q

of IL-1, TNFa and IL-6, which are capable of chemokine induction?

A

all EXCEPT IL-6

Q

what are lectins?

A

sugars that bind to other sugars

Q

are mucins mostly sugar or mostly protein?

A

mostly sugar

Q

selectins have what 2 domains?

A

cysteine-rich and

2. lectin domain

Q

Ig-superfamily CAMs are recognizable by their _____ held together by ____ bonds

A

loops; disulphide (Ig domains)

Q

CC chemokines have 2 ___ residues with ___ in between

A

cystine; nothing

Q

CXC chemokines have 2 ___ domains with ___ in between

A

cysteine; amino acid

Q

CCL is the ___ and CCR is the ___

A

ligand; receptor

Q

t/f the CXCR1 is found on neutrophils

A

t

Q

where are CXCR2 found?

A

many innate immune cells, especially granulocytes

Q

CXCR4 is the ___ co-receptor

A

HIV

Q

CCR1 is found on most ___

A

leukocytes

Q

CCR2 is found on most ____, ____ and ___ cells

A

monocytes, DC, and endothelial

Q

CCR3 is found on ___ and ___ cells

A

eosinophils and basophils

Q

release of ____ through the endothelium will start the rolling process and the chemotraction of the neutrophil

A

chemokines

Q

activation of neutrophils allows them to have high affinity form of some ___

A

CAMs

Q

selectins on inflammed endothelial cells bind to ____ on neutrophils, which starts the rolling process by tethering the neutrophil

A

mucins

Q

the ___ and ___ ig superfamily CAMs are responsible for grabbing the neutrophils for good (neutrophol arrest)

A

VCAM and ICAM-1

Q

MIP-1B attracts naive T cells to the ___

A

lymph node

Q

RANTES attracts memmory T cells to the

A

site of infection or site where infection had been before

Q

t/f there are different adhesion molecules for different parts of the body

A

true