Lecture 5: Inflammation and Leukocyte Migration Flashcards
1
Q
what causes the inflammatory response in general?
A
local injury or tissue trauma
2
Q
what 4 physical things characterize the inflammatory response?
A
- redness (rubor)
- heat (calor)
- swelling (tumor)
- pain (dolor)
3
Q
t/f the inflammatory response involves various leukocytes, and soluble and membrane-bound molecules
A
t
4
Q
in the inflammatory response, CAMs are crucial for _____ interactions during inflammation
A
leukocyte-tissue
5
Q
CAMs include _____ (4)
A
- selectins
- mucins
- integrins
- immunoglobulin-superfamily CAMs
6
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
7
Q
when neutrophils and phagocytes migrate to the site of inflammation, this is called _____
A
chemotaxis
8
Q
what 2 molecules are involved in neutrophil rolling?
A
L-selectin and PSGL-1
8
Q
what 2 molecules are involved in neutrophil rolling?
A
L-selectin and PSGL-1
9
Q
what 2 molecules are involved in neutrophil rolling?
A
L-selectin and PSGL-1
10
Q
what chemokines are involved in neutrophil activation?
A
IL-8 and macrophage inflammatory protein 1b (MIP-1b (akaCCL4))
10
Q
what chemokines are involved in neutrophil activation?
A
IL-8 and macrophage inflammatory protein 1b (MIP-1b (akaCCL4))
10
Q
what chemokines are involved in neutrophil activation?
A
IL-8 and macrophage inflammatory protein 1b (MIP-1b (akaCCL4))
10
Q
what chemokines are involved in neutrophil activation?
A
IL-8 and macrophage inflammatory protein 1b (MIP-1b (akaCCL4))
10
Q
what chemokines are involved in neutrophil activation?
A
IL-8 and macrophage inflammatory protein 1b (MIP-1b (akaCCL4))
11
Q
what molcules are involved in neutrophil adhesion?
A
LFA-1 and MAC-1
12
Q
what immune cells are typically the first to the site of inflammation?
A
neutrophils
13
Q
what do neutrophils respond to?
A
- C5a
- bacterial peptides containing N-formyl peptides
- leukotrienes in inflammed tissues
14
Q
what molecule is involved in rolling inflammatory monocytes?
A
L-selectin
15
Q
what chemokines are involved with activation of inflammatory monocytes?
A
monocyte-chemotractant protein-1 (MCP-1, CCL-2)
16
Q
what is the molecule involved with adhesion of inflammatory monocytes?
A
VLA-4
17
Q
what molecules are involved in rolling naive lymphocytes?
A
L-selectin, LFA-1, VLA-4
18
Q
what chemokines are involved in activation of naive lymphocytes?
A
CCL21, CCL19 and CXCL12 (for T cells) and CXCL13 (for B cells)
19
Q
what molecules are involved in naive lymphocyte adhesion?
A
LFA-1 and VLA-4
20
naive lymphocytes travel across ____ to enter the lymph node
high-endothelial venules
21
give 3 examples of selectins
L, E, and P selectins
22
what are selectins?
glycoproteins that bind specific carbohydrate groups
23
give and example of a specific carb group selectins bind to and how they bind
sialyl-Lewis x via a lectin-like domain
24
what are mucins?
glycosylated proteins that present sialyl-Lewisx and other carb groups to selectins
25
what are integrins?
cell surface heterodimeric proteins that bind extracellular matric molecules (like fibronectin) and ICAMs
26
what are ICAMs?
immunoglobulin-superfamily glycoproteins that bind integrins
27
give an example of a mucin-like CAM
CD34
28
give 3 examples of Ig-superfamily CAMs
1. ICAM-1,-2,-3
2. VCAM-1
3. MAdCAM-1
29
MAdCAM-1 has both ___ and ___ like properties
mucin-like and ig-superfamily
30
give 3 examples of integrins
1. a4B1 (VLA-4, LPAM-2)
2. aLB2 (LFA-1)
3. aMB2 (CR4, p150/95)
31
chemokines control what 3 leukocyte functions?
1. adhesion
2. chemotaxis
3. actvation
32
chemokines are ___ expressed and are also produced in response to ___
constitutively; inflammation
33
most chemokines belong to ____ or ___ subgroups
CC or CXC
34
what is the structure of chemokine receptors?
7-membrane spanning proteins that signal through hetrodimeric G proteins
35
t/f individual chemokine receptors are able to bind more than one chemokine
t
36
chemokine receptor expression is limited to certain cell types to confer ___
specificity to the action of given chemokines
37
what are the CXC subgroups of the CXCR1 chemokine receptors?
IL-8 (CXCL 8) and GCP-2 (CXCL 6)
38
what are the CXC subgroups of the CXCR2 chemokine receptor?
IL-8 (CXCL 8), Gro-a (CXCL 1), Gro-B (CXCL 2), gro-y (CXCL 3), NAP-2 (CXCL 7) and ENA-78 (CXCL5)
39
what are the CXC subgroups of the CXCR4 (CXCL11) chemokine receptor?
SDF-1 (CXCL12)
40
give an example of a chemokine that binds to the CCR1 chemokine receptor
RANTES (CCL5)
41
give an example of a chemokine that binds to the CCR2 chemokine receptor
MCP-1 (CCL2)
42
give an example of a chemokine that binds to the CCR3 chemokine receptor
RANTES (CCL5)
43
____ and ____ mediate the migration of leukocytes across the endothelial cell layer of blood vessels
chemotractants and CAM interactions
44
blood-borne neutrophils and monocytes enter sites of inflammation by a process called ___
extravasation
45
cytokines and other products of inflammation cause endothelial cells to increase ____ expression
CAM
46
neutrophil rolling is promoted by _____ interactions
selectin-mucin
47
chemokines such as ___ activate neutrophils
IL-8
48
integrins on activated neutrophils assume a ____ conformation that allows neutrophil arrest and adhesion to ____
high affinity; immunoglobulin-superfamily CAMs
49
selectins are important in what phase of neutrophil rolling and extravasation?
rolling
50
during neutrophil extravasation, chemokines induce ____ change of neutrophils and clustering of ___
conformational; integrins
51
during neutrophil extravasation, chemokines induce ____ change of neutrophils and clustering of ___
conformational; integrins
52
recirculation of lymphocytes from blood to bone marrow, spleen, lymph nodes and tertiary extralymphoid tissues occurs at least once every ____
24 hours
53
what is the point of lymphocyte recirculation?
ensures that the greatest number of antigen-specific lymphocytes have the opportunity to encounter and interact with antigen in lymphoid tissues
54
migration of lymphocytes into lymph nodes takes place across ____
high endothelial venules
55
lymphocyte rolling during lymphocyte extravasation is promoted by ____
weak interactions between lymphocyte L-selectin and endotheial cell mucin
56
what is the role of chemokines constitutively expressed by endothelial cells in lymphocyte extravasation?
activate lymphocytes, causing integrins to assume a high affinity conformation
57
what is the role of integrins in lymphocyte extravasation?
mediate lymphocyte arrest and adhesion to immunoglobulin-superfamily CAMs
58
transendothelial migration of lymphocytes is mediated by ___ molecules
junctional adhesion
59
what is the function of homing receptors on lymphocytes?
recognoze specific CAMs to mediate the differential migration of lymphocyte subsets into different tissues
60
give 2 examples of chemokines involved in lymphocyte homing and trafficking and their role
1. MIP-1B (attracts naive T cells)
| 2. RANTES (attracts memory T cells)
61
naive lymphocytes do not have ____ homing, so they are trafficked to ___
tissue-specific; secondary lymphoid tissues
62
effector lymphocytes traffic to sites of ___
inflammation
63
effector lymphocytes traffic to sites of ___
inflammation
64
where do memory lymphocytes home to ?
the tissue type where a specific antigen was first encountered
65
what are 3 important lipid mediators of inflammation? What produces them?
1. thromboxane
2. prostaglandins
3. leukotrienes
4. tissue mast cell and macrophages
66
what is the function of thromboxane?
vasoconstriction and platelet aggregation
67
what are the functions of prostaglandins?
increase vascular permeability, vascular dilation and neutrophil chemotaxis
68
what are the functions of leukotrienes C4, D4, and E4?
mediate lung inflammation
69
what is the function of leukotriene B4?
causes neutrophil chemotaxis
70
what are the functions of platelet activation factor (a lipid mediator of inflammation)
platelet aggregation, neutrophil activation, and eosinophil chemotaxis
71
chemokines, anaphylatoxins, proinflammatory cytokines and interferon-y are all ___
mediators of inflammation
72
what are the functions of chemokines as mediators of inflammation?
1. attract leukocyte subsets to sites of inflammation
| 2. regulate the expression and conformation of CAMs
73
what are the functions of anaphylatoxins (C3a and C5a) as inflammatory mediators?
trigger tissue mast cell release of histamine, leading to contraction of smooth mucle and increased vascular permeability
74
what are the functions of proinflammatory mediators TNF-a, IL-1 and IL-6?
have multiple redundant effects including fever, acute phase protein synthesis, increased CAM expression and increased vascular permeability during acute inflammation
75
what are the functions of IFN-y and TNF-a as inflammatory mediators?
important in chronic inflammation and can cause tissue damage
76
is IL-1 pyrogenic?
yes
77
is TNF-a pyrogenic?
yes
78
is IL-6 pyrogenic?
yes
79
can IL-1 trigger synthesis of acute phase proteins by teh liver?
yes
80
can TNF-a trigger synthesis of acute phase proteins by the liver
yes
81
can IL-6 trigger synthesis of acute phase proteins by teh liver?
yes
82
of IL-1, TNFa and IL-6, which can increase vascular permeability?
all
83
of IL-1, TNFa, and IL-6, which can cause increased adhesion molecules on vascular endothelium?
all EXCEPT IL-6
84
of IL-1, TNFa and IL-6, which are capable of chemokine induction?
all EXCEPT IL-6
85
what are lectins?
sugars that bind to other sugars
86
are mucins mostly sugar or mostly protein?
mostly sugar
87
selectins have what 2 domains?
1. cysteine-rich and
| 2. lectin domain
88
Ig-superfamily CAMs are recognizable by their _____ held together by ____ bonds
loops; disulphide (Ig domains)
89
CC chemokines have 2 ___ residues with ___ in between
cystine; nothing
90
CXC chemokines have 2 ___ domains with ___ in between
cysteine; amino acid
91
CCL is the ___ and CCR is the ___
ligand; receptor
92
t/f the CXCR1 is found on neutrophils
t
93
where are CXCR2 found?
many innate immune cells, especially granulocytes
94
CXCR4 is the ___ co-receptor
HIV
95
CCR1 is found on most ___
leukocytes
96
CCR2 is found on most ____, ____ and ___ cells
monocytes, DC, and endothelial
97
CCR3 is found on ___ and ___ cells
eosinophils and basophils
98
release of ____ through the endothelium will start the rolling process and the chemotraction of the neutrophil
chemokines
99
activation of neutrophils allows them to have high affinity form of some ___
CAMs
100
selectins on inflammed endothelial cells bind to ____ on neutrophils, which starts the rolling process by tethering the neutrophil
mucins
101
the ___ and ___ ig superfamily CAMs are responsible for grabbing the neutrophils for good (neutrophol arrest)
VCAM and ICAM-1
102
MIP-1B attracts naive T cells to the ___
lymph node
103
RANTES attracts memmory T cells to the
site of infection or site where infection had been before
104
t/f there are different adhesion molecules for different parts of the body
true
