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Phase I > R&C Chapter 3- Inflammation & Repair > Flashcards

R&C Chapter 3- Inflammation & Repair Flashcards

1
Q

What triggers leukocyte margination?

A

Stasis

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2
Q

What receptor type mediates rolling?

A

Selectins (CD62)

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3
Q

What receptor type mediates adhesion?

A

Integrin

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4
Q

What do Weibel-Palade Bodies contain?

A 
Von Willebrand Factor
P-selectin
IL-8
Eotaxin-3
Endothelin-1
Angiopoietin-2
Osteoprotegrin
CD63/lamp3 (P-selectin cofactor)
a-1,3-fucosyltransferase VI
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5
Q

Which cells contain L-selectin/CD62L?

A 
Leukocytes:
Neutrophils
Monocytes
T cells (naive and central memory)
B cells (naive)
Trophoblasts
Blastulas
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6
Q

What is the ligand for L-selectin and which cell expresses it?

A

Sialyl-Lewis X/PNAd on:
GlyCAM-1
CD34
MAdCAM-1

Endothelial cells, esp. HEV
Uterine cells

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7
Q

What cells contain E-selectin/CD62E?

A

Endothelial cells

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8
Q

What molecules increase E-selectin expression and which cells secrete them?

A

TNF, IL-1

Activated macrophages

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9
Q

What is the ligand for E-selectin and which cells express it?

A

Sialyl-Lewis X (Ex. CLA) on glycoproteins (ESL-1, PGSL-1)

Neutrophils, monocytes, T-cells (effector, memory)

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10
Q

What cells express P-selectin/CD62P?

A

Platelets and endothelial cells

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11
Q

What molecules increase P-selectin expression?

A

TNF, IL-1

Histamine or thrombin

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12
Q

What is the ligand for P-selectin/CD62P and which cells express it?

A

Sialyl-Lewis X on glycoproteins (PGSL-1, GlyCAM-1)

Neutrophils, monocytes, T-cells (effector, memory)

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13
Q

What is the alternative name for LFA-1?

A

CD11aCD18

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14
Q

What is the alternative name for MAC-1?

A

CD11bCD18

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15
Q

What is the alternative name for VLA-4?

A

CD49dCD29

a4B1

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16
Q

What cells express LFA-1?

A

Leukocytes:
Neutrophils
Monocytes
T cells (naive, effector, memory)

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17
Q

What are the ligands for LFA-1 and which cells express them?

A

ICAM-1 (CD54)
ICAM-2 (CD102)
Activated endothelium

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18
Q

What cells express MAC-1?

A

Monocytes

Dendritic cells

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19
Q

What are the ligands for MAC-1 and which cells express them?

A

ICAM-1 (CD54)
ICAM-2 (CD102)
Activated endothelium
Leukocytes

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20
Q

What molecules mediate extravasation?

A

CD31 (PECAM-1)
CD99
JAM A and C

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21
Q

What cells express CD31 (PECAM-1)

A

Endothelial cell junctions
Platelets
Leukocytes

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22
Q

What is the ligand for CD31?

A

CD31 (homotypic interaction)

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23
Q

What type of integrin is VLA-4?

A

B1

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24
Q

Activation of which molecules leads to actin polymerization during leukocyte chemotaxis?

A

Guanosine triphosphates Rac/Rho/cdc42

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25
Q

What types of receptors mediate phagocyte recognition and attachment?

A

Mannose receptors
Scavenger receptors
Opsonin receptors

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26
Q

What does lectin bind?

A

Terminal mannose and fucose residues of glycoproteins and glycolipids (common components of microbial cell walls)

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27
Q

What do scavenger receptors bind?

A

modified LDL

Variety of microbes

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28
Q

What is an example of a scavenger receptors?

A

MAC-1

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29
Q

What opsonins are recognized by opsonin receptors?

A

IgG antibodies
C3b
Mannose

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30
Q

What enzyme converts arginine to NO?

A

Nitric oxide synthase

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31
Q

How does hypochlorite kill microbes?

A

Halogenation

Lipid peroxidation

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32
Q

How is iNOS induced?

A

Macrophages and neutrophils are activated by cytokines (ex. IFN-y) or microbial products

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33
Q

What are the B2 integrins, and what CD11 subunit do they differ in?

A

LFA-1 (Cd11aCD18)
Mac-1 (CD11bCD18)
p150,95 (CD11cCD18)
adB2 (CD11dCD18)

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34
Q

What neutrophil receptor binds hyaluronan on luminal surface of endothelial cells?

A

CD44

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35
Q

Neutrophil receptor CD44 binds what component of endothelial cells/ECM?

A

SHAP (serum-derived hyaluronan-associated protein)

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36
Q

What molecules does transcytosis transport?

A

Albumin
LDL
Metalloproteinases
Insulin

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37
Q

What stimulates increased transcytosis?

A

VEGF

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38
Q

What triggers endothelial cell contraction leading to interendothelial cell gaps?

A 
Histamine
Serotonin
Bradykinin
Substance P (tachykinin)
Angiotensin II 
Leukotrienes
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39
Q

What triggers endothelial cell cytoskeletal rearrangement leading to interendothelial cell gaps?

A

TNF, IL-1
Interferon-y
Hypoxia

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40
Q

What molecule cleaves L-selectin molecules from neutrophils to allow for stable adhesion?

A

ADAM17

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41
Q

ADAM17 cleaves what neutrophil molecule to allow what process to happen?

A

L-selectin

Stable Adhesion

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42
Q

What molecules stimulate redistribution of P-selectin from Weibel-Palade bodies to cell surface?

A

Histamine

Thrombin

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43
Q

Endothelial P-selectin binds which leukocyte adhesion molecule?

A

Sialyl-Lewis X on PGSL-1

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44
Q

Endothelial E-selectin binds which leukocyte adhesion molecule?

A

Sialyl-Lewis X on ESL-1, PGSL-1 and CLA

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45
Q

Endothelial ICAM-1 binds which leukocyte adhesion molecule?

A

Integrins:
LFA-1 (CD11aCD18)
MAc-1 (CD11bCD18)

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46
Q

Endothelial PECAM-1 binds which leukocyte adhesion molecules?

A

PECAM-1

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47
Q

Endothelial JAM A binds which leukocyte adhesion molecules?

A

JAM A

LFA-1

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48
Q

Endothelial JAM C binds which leukocyte adhesion molecules?

A

JAM B

Mac-1

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49
Q

What is an alternative name for ICAM-1?

A

CD54

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50
Q

What is an alternative name for ICAM-2?

A

CD102

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51
Q

What is an alternative name for VCAM-1?

A

CD106

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52
Q

Familial Mediterranean Fever is characterized by a SNP in the ____ domain of the ___ receptor, leading to increased expression and secretion of ____.

A

Pyridine
Inflammasome
IL-1B

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53
Q

What cells produce Angiotensin II?

A

Endothelial cells

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54
Q

What are the functions of angiotensin II?

A

Acts on CNS –> increased vasopressin –> vasoconstriction

Increases aldosterone –> increased Na (thus water) reabsorption and K secretion

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55
Q

What are examples of exogenous chemoattractants

A

Bacterial products (ex. N-formylmethionine terminal amino acids)

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56
Q

What are examples of endogenous chemoattractants?

A

Cytokines (esp. IL-8)
Complement (esp. C5a)
Arachidonic acid metabolites (esp. LTB4)

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57
Q

What general receptor type do chemotactic agents bind on leukocytes?

A

G-protein coupled receptors

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58
Q

What is the CD name for Gp150,95?

A

CD11cCD18

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59
Q

What is the CD name for adB2?

A

CD11dCD18

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60
Q

What is the CD name for PECAM-1?

A

CD31

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61
Q

What is the CD name for L-selectin?

A

CD62L

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62
Q

What is the CD name for E-selectin?

A

CD62E

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63
Q

What is the CD name for P-selectin?

A

CD62P

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64
Q

What is the CD name for the hyaluronic acid receptor?

A

CD44

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65
Q

What is the CD name for JAM A?

A

CD321

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66
Q

What is the CD name for Jam B?

A

CD322

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67
Q

What are the main functions of the JAM molecules?

A

Transendothelial migration

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68
Q

B1 integrins are what CD class?

A

CD29

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69
Q

B2 integrins are what CD class?

A

CD18

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70
Q

B3 integrins are what CD class?

A

CD61

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71
Q

Selectins are what CD class?

A

CD62

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72
Q

CD99 is present on what cells?

A

Endothelial cells
Leukocytes
Monocytes

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73
Q

CD99 binds to what cells?

A

Endothelial cells

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74
Q

CD44 is present on what cells?

A

Leukocytes (inc. PMNs)

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75
Q

JAM A is present on what cells?

A

Endothelial junctions
Leukocytes
Platelets

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76
Q

The targets of JAM A binding are present on what cells?

A

Leukocytes

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77
Q

Jam B is present on what cells?

A

HEV
Endothelial junctions
Leukocytes
Platelets

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78
Q

The targets of JAM B binding are present on what cells?

A

Leukocytes

Dendritic cells

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79
Q

What does JAM B bind?

A

JAM B & C

VLA-4

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80
Q

What cells express ICAM-1?

A 
Endothelial cells
Epithelial cells
Schwann cells
Neutrophils
Macrophages & monocytes
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81
Q

What molecules does ICAM-1 bind?

A

B2 integrins

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82
Q

The targets of ICAM-1 binding are present on what cells?

A

Leukocytes

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83
Q

ICAM-2 is expressed by what cells?

A

Endothelial cells

Lymphocytes

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84
Q

What molecules does ICAM-2 bind?

A

B2 integrins

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85
Q

The targets of ICAM-2 binding are present on what cells?

A

Leukocytes

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86
Q

ICAM-3 is expressed by what cells?

A

Endothelial cells
Lymphocytes
Neutrophils
Monocytes

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87
Q

What molecules does ICAM-3 bind?

A

B2 integrins

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88
Q

The targets of ICAM-3 binding are present on what cells?

A

Leukocytes

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89
Q

ICAM-4 is expressed by what cells?

A

Erythrocytes

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90
Q

What molecules does ICAM-4 bind?

A

B2 integrins

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91
Q

The targets of ICAM-4 binding are present on what cells?

A

Leukocytes

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92
Q

ICAM-5 is expressed by what cells?

A

Some neurons

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93
Q

What molecules does ICAM-5 bind?

A

B2 integrins

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94
Q

The targets of ICAM-5 binding are present on what cells?

A

Leukocytes

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95
Q

VCAM-1 is expressed by what cells?

A

Endothelial cells

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96
Q

What molecules does VCAM-1 bind?

A

VLA-4

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97
Q

The target of VCAM-1 binding is present on what cells?

A

Leukocytes (except neutrophils)

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98
Q

PECAM-1 is expressed by what cells?

A

Endothelial cells

Leukocytes

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99
Q

What molecule does PECAM-1 bind?

A

PECAM-1/CD31 (homotypic interaction)

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100
Q

The target of PECAM-1 binding is present on what cells?

A

Endothelial cells

Leukocytes

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101
Q

MAdCAM-1 is expressed by ehat cells?

A

Endothelial (mucosal)

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102
Q

MAdCAM-1 binds what molecules?

A

L-selectin

a4(B7)

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103
Q

The targets of MAdCAM-1 binding are present on what cells?

A

Leukocytes

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104
Q

What does avB8 bind and where?

A

Laminin

ECM

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105
Q

What cells express a4b7?

A

Endothelial cells

Lymphocytes

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106
Q

What does a4b7 bind?

A

MAdCAM-1

VCAM-1

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107
Q

The targets of a4b7 binding are present on what cells?

A

Endothelial cells (esp. intestinal mucosa, GALT)

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108
Q

What cells express aeB7?

A

Intraepithelial cells

Lymphocytes

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109
Q

What does aeB7 bind?

A

E-cadherin

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110
Q

The targets of aeB7 binding are present on what cells?

A

Endothelial cells

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111
Q

What cells express avB6?

A

Epithelial cells

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112
Q

What does avB6 bind and where?

A

Fibronectin

ECM

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113
Q

What cells express avB5?

A

Endothelial cells

Epithelial cells

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114
Q

What does avB5 bind and where?

A

Vitronectin

ECM

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115
Q

What cells express a6B4?

A

Endothelial cells

Schwann cells

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116
Q

What does a6B4 bind and where?

A

Laminin

ECM

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117
Q

What is the CD name for avB3?

A

CD41CD61

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118
Q

What is the CD name for aIIbB3?

A

CD41CD61

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119
Q

What cells express aIIbB3?

A

Platelets

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120
Q

What molecules does aIIbB3 bind?

A

Fibrinogen

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121
Q

The target of aIIbB3 binding is present on what cells?

A

Endothelial cells

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122
Q

What cells express avB3?

A

Platelets
Endothelial cells
Macrophages
Monocytes

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123
Q

What does avB3 bind and where?

A

Fibronectin

ECM

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124
Q

What cells express Gp150,95?

A

Leukocytes

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125
Q

What does Gp150,95 bind?

A

ICAM-1

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126
Q

The target of Gp15095 binding is present on what cells?

A

Endothelial cells

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127
Q

The target of Mac-1 binding is present on what cells?

A

Endothelial cells

Leukocytes

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128
Q

The target of LFA-1 binding is present on what cells?

A

Endothelial cells

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129
Q

What cells express adB2?

A

Macrophages

CD8+ T cells

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130
Q

What does adB2 bind?

A

ICAM-3

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131
Q

The target of adB2 binding is present on what cells?

A

Endothelial cells

Leukocytes

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132
Q

What is the CD name for VLA-1?

A

CD49aCD29

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133
Q

What is the CD name for VLA-2?

A

CD49bCD29

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134
Q

What is the CD name for VLA-3?

A

CD49cCD29

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135
Q

What is the CD name and a/b for VLA-4?

A

CD49dCD29

a4B1

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136
Q

What is the CD name for VLA-5?

A

CD49eCD29

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137
Q

What is the CD name for VLA-6?

A

CD49fCD29

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138
Q

What is the only VLA that is expressed by leukocytes instead of endothelial cells?

A

VLA-4

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139
Q

All VLAs except VLA-4 are expressed on what cell type?

A

Endothelial cells

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140
Q

What cells express VLA-1?

A

Endothelial cells

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141
Q

What cells express VLA-2?

A

Endothelial cells

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142
Q

What cells express VLA-3?

A

Endothelial cells

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143
Q

What cells express VLA-5?

A

Endothelial cells

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144
Q

What cells express VLA-6?

A

Endothelial cells

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145
Q

What cells express VLA-4?

A

Leukocytes (except PMNs)

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146
Q

What does VLA-1 bind and where?

A

Collagen

ECM

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147
Q

What does VLA-2 bind and where?

A

Collagen

ECM

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148
Q

What does VLA-3 bind and where?

A

Fibronectin

ECM

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149
Q

What does VLA-5 bind and where?

A

Fibronectin

ECM

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150
Q

What does VLA-6 bind and where?

A

Laminin

ECM

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151
Q

What does VLA-4 bind?

A

VCAM-1

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152
Q

The target of VLA-4 binding is present on what cells?

A

Endothelial cells

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153
Q

Mast cells and basophils share what CD+ common precursor?

A

CD34+

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154
Q

Mucosal, but not connective tissue, mast cells can respond to what type of immune-response?

A

Th2

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155
Q

Th2 responses can trigger which type of mast cells?

A

Mucosal (not connective)

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156
Q

What receptor is highly expressed on mast cells and what does it bind?

A

FceRI

IgE

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157
Q

What molecule released from sensory/C-reactive nerve fibers can trigger mast cell degranulation?

A

Substance P

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158
Q

What molecule do basophils lack compared to mast cells?

A

heparin

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159
Q

What are the main products secreted by basophils?

A

Histamine
PAF
FceRI

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160
Q

What receptors are expressed by basophils?

A

FceRI
CD40L
CCR3 (eotaxin)

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161
Q

Which molecules lead to increased bone marrow release of neutrophils and granulopoiesis?

A

TNF, IL-1

GM-CSF, G-CSF, IL-3

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162
Q

How do neutrophils function in hypoxic conditions?

A

Stabilization of HIF-1a

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163
Q

Neutrophils have receptors for what molecules?

A 
PAF
C5a
IL-8
Substance P
Leukotrienes
Kallikrein
GM-CSF
TNF
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164
Q

During neutrophil migration, binding of leukocyte adhesion molecule to ligand triggers which signaling pathway?

A

MAPK and G proteins

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165
Q

What enzyme is involved in neutrophil oxidative burst?

A

NADPH oxidase

166
Q

What reaction does myeloperoxidase catalyze?

A

H2O2 –> hypochloroud acid

167
Q

What molecules does NADPH oxidase produce?

A

Superoxide free radicals

168
Q

What molecules mediate phagosome-lysosome fusion?

A

Calmodulin and SNARE

169
Q

What is peroxynitrate formed from?

A

NO and superoxide anions

170
Q

NO and superxide anions form what?

A

Peroxynitrate

171
Q

How does lactoferrin inhibit growth of phagocytosed bacteria?

A

Sequesters free iron

172
Q

What are contained with the neutrophil azurophilic/primary granules?

A 
Myeloperoxidase
Phospholipase A2
Defensins
Lysozymes
ECM degraders
173
Q

What are contained within neutrophil specific/secondary granules?

A 
Lysozymes
ECM degraders
Lactoferrin
Plasminogen activator
Histaminase
Alkalkine phosphatase
Phospholipase A2
CD11CD18
174
Q

What are the functions of acid proteases?

A

Degrade bacteria and debris within phagolysosomes

175
Q

What are the function of neutral proteases?

A 
Hydrolyze bacterial cell wall components
Degrade ECM
Cleaves C3, 5
Defensins: toxic to microbes
Cathelicidins: AMP
176
Q

What does lysozyme hydrolyze?

A

Muramic acid-N-acteylglusamine bond (bacterial coat)

177
Q

What is different about reptile and bird neutrophils?

A

Absent to decreased myeloperoxidase

178
Q

What neutrophil molecule is lacking in dogs, cats, mice, pigs and horses?

A

Alpha-defensins

179
Q

What neutrophil molecule do cattle and sheep have less of?

A

Lysoszyme

180
Q

What is the signaling pathway of chemotaxis?

A

GPCR –> guanosine triphosphates Rac/Rho/cdc42 –> actin polymerization

181
Q

What cells produce histamine?

A

Mast cells
Platelets
Basophils

182
Q

What are the receptors for histamine and where are they located?

A

H1: endothelium
H2: gastric mucoda
H3: Nerve terminals
H1,4: leukocytes

183
Q

What are the actions of histamine?

A

Vasodilation
Increased vascular permeability
Endothelial activation
Smooth muscle contraction

184
Q

What cells produce serotonin?

A

Mast cells
Platelets
Neuroendocrine

185
Q

What is another name for serotonin?

A

5-hydroxytryptamine

186
Q

What are the actions of serotonin?

A

Vasoconstriction (minimal)
Smooth muscle contraction
Increased vascular permeability
Neurotransmitter

187
Q

What cells produce prostaglandins?

A

Leukocytes (esp. mast cells, macrophages)

Endothelial cells

188
Q

What are the actions of prostaglandins?

A

Vasodilation

Pain, fever

189
Q

What cells produce leukotrienes?

A

Leukocytes

Esp. mast cells

190
Q

What are the actions of leukotrienes?

A

Increased vascular permeability
Chemotaxis
Leukocyte adhesion and activation

191
Q

Where is kinogen produced?

A

Liver

192
Q

Where are tachykinins produced?

A

Sensory afferent nerve fibers of lungs and alimentary

193
Q

What are the stimuli for histamine release?

A 
Physical injury: heat, cold
ATP
Antibody binding
C3a, C5a
Neuropeptides: substance P
Cytokines IL-1, IL-8
IgE
Eosinophil major basic protein & cationic protein
194
Q

Stimulation of what histamine receptor is common in allergic rhinitis?

A

H1

195
Q

What is the plasmin kinin pathway of bradykinin formation?

A

Protein complex of HMWK + factor 11 + prekallikrein –> complex contacts negatively charged surface –> factor 12 binds to complex –> factor 12 activated –> kallikrein activated –> kallikrein activates HMWK to bradykinin

196
Q

What is the tissue kinin pathway of bradykinin formation?

A

Tissue kallikrein acts on LMWK –> lysyl bradykinin –> bradykinin

197
Q

What is the bradykinin receptor in inflammed tissue?

A

B1R (GPCR)

198
Q

What is the bradykinin receptor in normal tissue?

A

12R (GPCR)

199
Q

What enzymes degrade bradykinin?

A

Aminopeptidase M
Neutral endopeptidase
Carboxypeptidase (kininase I)
Angiotensin-converting enzyme (kininase II)

200
Q

What inhibits kallikrein (activator of bradykinin)?

A

C1-INH esterase (serum a2 macroglobulin)

201
Q

What is the function of tachykinin substance P?

A

Vasoconstriction & dilation
Increased vascular permeability
Mast cell, eosinophil & basophil activation
Pain

202
Q

What is the function of tachykinins neurokinin A & B?

A

Allergic reactions and asthma

203
Q

What is the receptor for substance P and what cells express it?

A

NK-1R

Mast cells, epithelial cells, endothelial cells, macrophages

204
Q

What downregulates NK-1R expression?

A

Increased substance P expression

205
Q

Binding of substance P to what receptor on nerve fibers leads to decreased expression?

A

H3

206
Q

Capsaicin binds to what receptor on afferent sensory nerves to trigger substance P release?

A

Vanilloid receptor-1

207
Q

What enzyme releases arachadonic acid from the plasma membrane?

A

Activated phospholipase A2

208
Q

Steroids inhibit what enzyme in the arachadonic acid metabolism pathway?

A

Phospholipase A2

209
Q

What is the action of cyclooxygenase?

A

Convert arachadonic acid to prostaglandin G2 (PGG2)

210
Q

What activates phospholipases?

A

Increased cytoplasmic calcium
Kinases
C5a

211
Q

Which eicosanoids result in vasodilation?

A

PGI2, PGE1, PGE2, PGD2

LTB4

212
Q

What eicosanoids result in smooth muscle contraction?

A

PGF2A (uterine, bronchiole, arteriole)
PGD2 (bronchiole)
LTC,D,E4 (bronchospasm)

213
Q

What eicosanoid inhibits platelet aggregation?

A

PGI2 (prostacyclin)

PGE2 (at HIGH concentrations)

214
Q

What eicosanoid triggers platelet aggregation?

A

Thromboxane A2

PGE2 (at LOW concentrations)

215
Q

What eicosanoids result in vasoconstriction?

A

Thromboxane A2

LTC,D,E4

216
Q

What eicosanoids result in increased vascular permeability?

A

PGI2, PGE2

LTB, LTC,D,E4

217
Q

What eicosanoids are important for leukocyte chemotaxis and leukocyte adhesion?

A

PGD2

LTB4, 5-HPETE, 5-HETE

218
Q

What eicosanoid results in pain/hyperalgesia?

A

PGE2

219
Q

Which cyclooxygenase is constitutively expressed?

A

COX1

220
Q

Which cyclooxygenase is induced by inflammation?

A

COX2

221
Q

Where is COX3 located?

A 
Cerebral cortex (dogs and humans)
Rodent cerebral endothelia, heart, kidney, neurons
222
Q

What enzyme produces thromboxane A2?

A

Thromboxane synthase

223
Q

What enzyme produces prostacyclin?

A

Prostacyclin synthase

224
Q

Thromboxane synthase is particularly abundant in what cells?

A

Platelets

225
Q

Prostacyclin synthase is particular abundant in what cells?

A

Endothelial cells

226
Q

PGD2 is produced by what cells?

A

Mast cells

227
Q

PGE2 is produced by what cells?

A

Epithelial cells, fibroblasts, smooth muscle cells

228
Q

What receptor does PGE2 bind and what effect does it have on T cells?

A

EP4

Th1 and Th17 differentiation

229
Q

What is the function of 5-lipoxygenase?

A

Convert arachadonic acid to HPETE

230
Q

What is the function of 1,2-lipoxygenase?

A

Convert HPETE to lipoxins

231
Q

What are the role of lipoxins?

A

Suppress inflammation by inhibiting:
-leukocyte recruitment
-neutrophil chemotaxis (inhibit LTB4 activation of neutrophils)
- neutrophil endothelial attachment
-angiogenesis
-LTC4 induced vasoconstriction (–> vasodilation)
Stimulates macrophage attachment to endothelium

232
Q

What enzyme converts LTA4 to LTB4?

A

LTA4 hydrolase

233
Q

What enzyme converts LTA4 to LTC4?

A

LTC4 synthase

234
Q

What does LTA4 arise from?

A

HPETE

235
Q

What are the major effects of leukotrienes?

A

Increased vascular permeability
Leukocyte chemotaxis
Vasoconstriction

236
Q

What leukotriene is a major chemotactic factor for neutrophils and macrophages?

A

LTB4

237
Q

Which receptors do LTC,D,E4 bind and what do they mediate?

A

CysLT1&2

Bronchoconstriction and vasoconstriction

238
Q

What receptors does LTB4 bind and what does it mediate?

A

BLT1 and 2

Neutrophil chemotaxis

239
Q

Which eosinophil granule component inactivates leukotrienes?

A

Arylsulfatase

Acid phosphatase

240
Q

What omega-3 fatty acid product inhibits BLT1/LTB4 signaling?

A

Resolvin

241
Q

What molecule dampens LTC4 induced vasoconstriction?

A

Lipoxin A4

242
Q

What molecules inhibit LTB4 activation of neutrophils?

A

Lipoxins

243
Q

What is the physical difference between type 1 and 2 cytokines?

A

1: 4 alpha helices
2: 6 alpha helices

244
Q

What are the hematopoietic growth factors?

A 
IL-3
G-CSF
GM-CSF
IL-9
IL-11
Stem cell factor
245
Q

What is a chemotactic cytokine?

A

IL-8

246
Q

What are the principle actions of TNF?

A

Endothelial adhesion molecule expression, diapedesis
Leukocyte activation and cytokine secretion
Increase lipid/protein mobilization

247
Q

What are the principle actions of IL-1?

A

Similar to TNF (endothelial adhesion, cytokine secretion)
Fibroblast activation
Synovial, mesenchymal proliferation
Stimulate Th17 response

248
Q

What is the principle function of IL-17?

A

Recruitment of neutrophils and monocytes

249
Q

What cytokines are involved in the systemic acute phase response?

A

TNF, IL-1, IL-6

250
Q

What is the principle source of IL-17?

A

T lymphocytes

251
Q

What is the principal source of IL-12?

A

Dendritic cells

Macrophages

252
Q

What is the principal source of IFN-y?

A

T lymphocytes and NK cells

253
Q

What is the principal action of IL-12 in chronic inflammation?

A

Increased IFN-y production

254
Q

What is the principal action of IFN-y in chronic inflammation?

A

Macrophage activation (increased killing ability)

255
Q

What are the type I interferons?

A

IFN-a and IFN-B

256
Q

What are the type II interferons?

A

IFN-y

257
Q

What are the receptors of type I interferons?

A

IFNAR 1 and 2

258
Q

What are the receptors of type II interferons?

A

IFNGR 1 and 2

259
Q

What is the function of Type II interferons?

A

Amplify Th1 and Th17 response

Classical macrophage activation

260
Q

What is the function of Type I interferons?

A

Antiviral response

261
Q

What is the signaling pathway Type I interferons use?

A

ISGlyation pathway

262
Q

ISGlyation pathway activates what gene and what antiviral proteins (and what is their respective function)?

A 
ISG15
MxA protein: binds and traps viruses
OAS1: cleaves viral RNA
RNaseL: cleaves viral RNA
PKR: inhibits viral replication by inhibiting EIF-2a
263
Q

What is the glycoprotein name for aIIbB3 integrin?

A

GpIIbIIIa

264
Q

In the process of leukocyte vascular extravasation, which subset of leukocytes only express the B1 integrin Very Late Antigen 4 (VLA4 or a4B1)?

A

Lymphocytes

Monocytes

265
Q

Which leukocyte integrin and endothelial ligand pair are primarily responsible for leukocyte locomotion toward endothelial junctions?

A

MAC-1 and ICAM-1

266
Q

Which surface molecule expressed at the endothelial cell to endothelial cell junction is a NEGATIVE regulator of leukocyte transendothelial paracellular migration?

A

VE-cadherin

267
Q

What molecule is absent from the lateral border recycling compartment (LBRC) of endothelial cells?

A

VE-cadherin

268
Q

For which leukocyte is paracellular transendothelial migration NOT dependent upon PECAM-PECAM interaction?

A

Basophils

269
Q

What cell type expresses P-selectin glycoprotein 1?

A

Leukocytes

270
Q

Chemokines produced by endothelial cells and meant to activate leukocytes to activate additional surface integrins, are transported to the luminal side of endothelial cells and bind to which molecules on the endothelial cells?

A

Heparin sulfate glycosaminoglycans

271
Q

Chemokines bind to what receptor type on leukocytes?

A

G protein coupled receptors

272
Q

The majority of beta integrins bind to what?

A

ECM proteins

273
Q

What are the steps of leukocyte extravasation?

A 
Capture/tethering
Rolling
Activation
Adhesion
Locomotion
Diapedesis
Traversing basal lamina
Migration through ECM
274
Q

As neutrophils navigate through the basal lamina, which molecular interactions at the trailing edge allow them to seek out the low density portals?

A

Neutrophils: LFA (Cd11aCD18)
Pericytes: ICAM-1

275
Q

As the neutrophils moves forward through the basal lamina, what molecular interactions occur at the leading edge?

A

Neutrophil: VLA-3
ECM: fibronectin

276
Q

During transendothelial migration, homotypic interactions occur first between _____ and then later between _____.

A

First: PECAM-PECAM
Later: CD99-CD99

277
Q

Which other molecules have been shown to have a role in TEM by addition of antibodies against them?

A

CD: 47, 146, 155, 166

CLM-9

278
Q

What is contained within the lateral border recycling compartment of endothelial cells?

A

PECAM
CD99
JAM-A

279
Q

What molecules is present in the LBRC of HEV, but not other types of endothelial cells, and what is its function?

A

CLM-9

Lymphocyte TEM

280
Q

What are neutrophil chemokines?

A 
IL-8
IL-17
LTB4
PGD2
5HETE
PAF
C5a
N-formyl-peptides
281
Q

What molecules are expressed constitutively by HEVs?

A

CCL19 (R: CCR7)
CCL21 (R: CCR7)
CXCL12 (R:CXCR4)
CXCL13 (R: CXCR5)

282
Q

What cytokines activate endothelial cells and neutrophils to express adhesion molecules?

A 
IL-1
IL-6
TNF
C5a
PAF
PDGF
283
Q

Anthrax lethal toxin activates which inflammasome receptor?

A

NLRP1

284
Q

In sepsis, which molecules reduce activation of the NF-kB pathway?

A

IRAK-M
MyD88s
ABIN-3

285
Q

What cytokine induces C-reactive protein?

A

IL-6

286
Q

What cell type produces C-reactive protein?

A

Hepatocytes

287
Q

What is the function of C-reactive protein?

A

Bind microbial cell walls
Act as opsonins and fix complement
Bind chromatin and clear necrotic nuclear debris

288
Q

What cytokine inhibits macrophage secretion of MMPs?

A

IL-17

289
Q

What are the hematopoietic growth factors?

A

IL-3, 9, 11
G-CSF, GM-CSF
Stem cell factor

290
Q

What cells release high mobility group box protein-1 (HMGB-1)?

A

Monocytes and macrophages

All cells during necrosis (alarmins)

291
Q

What are HMGB-1s and what is their function?

A

Non-histone, nuclear, DNA-binding protein

Regulate gene expression and chromosomal architecture

292
Q

What receptors do HMGB-1s bind?

A

Macrophage receptor: RAGE

TLR2, 4

293
Q

HMGB-1 proteins induce release of what cytokines?

A

IL-1
TNFa
IFN-y

294
Q

What molecules interact with the hypothalamus to cause food aversion, hypophagia, anorexia, weight loss and sickness behavior?

A

HMGB-1
Systemic acute phase response cytokines: TNFa, IL-1, IL-6
PGE2

295
Q

CXC chemokines are chemotactic for what cells?

A

Neutrophils

296
Q

CXC chemokines are produced by what cells?

A

Activated macrophages

Endothelial cells

297
Q

What type of cytokine is IL-8?

A

CXC

298
Q

C-C chemokines are chemotactic for what cells?

A

Monocytes
Eosinophils
Basophils
Lymphocytes

299
Q

C chemokines are chemotactic for what cells?

A

Lymphocytes

300
Q

What is an example of a C chemokine?

A

Lymphotactin

301
Q

CX3C chemokines are chemotactic for what cells?

A

Monocytes

T cells

302
Q

What is an example of a CX3C chemokine?

A

Fractalkine

303
Q

What cell is fractalkine produced by?

A

Endothelial cells

304
Q

What is another name for MCP-1, and what is its receptor?

A

CCL2

CCR11

305
Q

What is another name for MIP-1a and what is its receptor?

A

CCL3

CCR1, CCR5

306
Q

What is another name for MIP-1B and what is its receptor?

A

CCL4

CCR5

307
Q

What is another name for RANTES and what is its receptor?

A

CCL5

CCR3, CCR5

308
Q

What is another name for eotaxin-1 and what is its receptor?

A

CCL11

CCR3, CCR11

309
Q

What is another name for eotaxin-2 and what is its receptor?

A

CCL24

CCR3

310
Q

What is another name for eotaxin-3 and what is its receptor?

A

CCL26

CCR3

311
Q

What is another name for IL-8 and what is its receptor?

A

CXCL8 or NAP-1

CXCR1, CXCR2

312
Q

What chemokine receptors are NOT expressed by memorty T lymphocytes?

A

CCR1-7

CXCR3, CXCR1

313
Q

How is the classical pathway triggered?

A

Fixation of C1 to Ab-Ag

314
Q

How is the alternative pathway triggered?

A

Activators that directly cleave C3:
Microbial: LPS, endotoxin, fungal cell wall polysaccharides
Plasma proteins: kallikrein, plasmin, factor 12a
Venom

315
Q

How is the lectin pathway triggered?

A

Mannose-binding lectins and ficolins binding to carbohydrates on microbes and directly activating C1 –> activates MASPS –> cleaves C4 and C2

316
Q

Which complement pathway is constitutively active at low levels?

A

Alternative

317
Q

What molecule extends the half-life of C3bBb?

A

Properdin

318
Q

What are the complement regulators?

A

C1 INH (C1 inhibitor)
DAF (Decay accelerating factor)
Factor H
CD59

319
Q

What is the function of C1?

A

C1q: binds Fc receptor of IgG or IgM
C1r: cleaves C1s
C1s: cleaves C4 and C2

320
Q

What is another name for classical C3 convertase?

A

C4bC2b

321
Q

What is the function of classical C3 convertase?

A

Cleave C3 into C3a + C3b

322
Q

What is another name for classical C5 convertase?

A

C4bC2bC3b

323
Q

What is the function of classical C5 convertase?

A

Cleaves C5 into C5a + C5b

324
Q

What is the function of C3a?

A

Anaphylatoxin
Chemotaxis
MAVS

325
Q

What is the function of C5a?

A

Anaphylatoxin
Induces endothelial adhesion molecule expression
Leukocyte chemoattractant
Activates lipoxygenase AA pathway

326
Q

What is the function of C3b and C3bi?

A

Opsonization and phagocytosis (via neutrophil CR1 and CR3)

Enhance immune memory and Ab response

327
Q

What is the function of C5b?

A

Anchor for MAC assembly

328
Q

What is the function of C6, C7, C8?`

A

MAC: allows for C9 polymerization, tube formation and insertion

329
Q

What is the function of C9?

A

MAC: forms channel portion of MAC

330
Q

What is another name for alternative C3 convertase?

A

C3bBb

331
Q

What is another name for alternative C5 convertase?

A

C3bBbC3b

332
Q

What factors are required for the formation of alternative C3 convertase?

A

Cleaved C3 (C3b portion)
Cleaved Factor B (Bb portion)
Factor D

333
Q

What is the function of C1 INH?

A

Blocks C1 activation (Classical Pathway)

334
Q

What is the function of DAF?

A

Prevent formation of C3 convertases

335
Q

What is the function of Factor H?

A

Inhibits alternative pathway activation by:

  • competing with factor B binding to C3b
  • accelerating decay of C3 convertase
  • co-factor for Factor-I mediated cleavage of C3b
336
Q

What is the function of CD59?

A

Inhibits formation of MAC

337
Q

What is the function of PAF?

A 
Platelet aggregation
Histamine release
Vasoconstriction and vasodilation
Bronchoconstriction
Leukocyte adhesion
Chemotaxis
Neutrophil degranulation and oxidative bursts
Increased vascular permeability
338
Q

What is the function of bradykinin?

A

Increased vascular permeability
Smooth muscle contraction
Vasodilation
Pain

339
Q

What is the source of alpha-defensins?

A

Neutrophils and Paneth cells

340
Q

What is the source of beta-defensins?

A

Neutrophils and epithelial cells

341
Q

What is the source of theta-defensins?

A

Primate neutrophils

342
Q

What is the function of alpha and beta defensins?

A

Mast cell degranulation
Induce IL-8 synthesis
T-cell chemotaxis
Activate T cells, macrophages and dendritic cells

343
Q

Which inflammatory mediators result in vasodilation?

A 
Histamine
Prostaglandins: PGI2, PGE1, PGE2, PGD2
LTB4
Bradykinin
Nitric oxide
344
Q

Which inflammatory mediators result in increased vascular permeability?

A 
Histamine
Serotonin
Bradykinin
Tachykinin (Substance P)
Angiotensin
Leukotrienes: B4, C4, D4, E4
PGE2
C3a, C5a
Fibrinopeptides and fibrin breakdown products
PAF
IL-1
TNF
Interferon-y
Hypoxia
345
Q

Which inflammatory mediators result in smooth muscle contraction?

A 
LTC4, LTD4, LTE4
PGF2, PGD2
PAF
Histamine
Serotonin
Bradykinin
C3a
346
Q

Which inflammatory mediators result in chemotaxis and leukocyte recruitment and activation?

A 
TNF, IL-1
IL-8
C3a, C5a
LTB4
PGD2
Alpha and beta defensins
Bacterial products: LPS, peptidoglycans, techoic acid
Collagenous lectins: ficolins, surfactant proteins A & D, mannose-binding lectin
347
Q

Which inflammatory mediators result in fever?

A

TNF, IL-1, IL-6

PGE2

348
Q

Which inflammatory mediators result in pain?

A

PGE2
Bradykinin
Substance P

349
Q

Which inflammatory mediators result in nausea?

A

IL-1, TNF

350
Q

Which inflammatory mediators result in the systemic acute phase response?

A

TNF
IL-1
IL-6
Type I interferons (a and B)

351
Q

What molecules classically activate macrophages?

A

IFN-y

Microbes: endotoxins, crystals, particulate matter

352
Q

What molecules alternatively activate macrophages?

A

IL-4

IL-13

353
Q

What do classically activated macrophages produce?

A

ROS, NO, lysosomal enzymes
IL-1, IL-12, IL-23, chemokines
Increased MHCII surface expression

354
Q

What do alternatively activated macrophages produce?

A

Growth factors
IL-10
TGF-B

355
Q

What molecules trigger macrophages to differentiate into regulatory macrophages?

A

IL-10

356
Q

What molecule secreted by classically activated macrophages amplifies the Th1 response?

A

IL-12

357
Q

Nodular/tuberculoid granulomas are mediated by what T cell response?

A

Th1

358
Q

What Mycobacterium species are associated with a nodular/tuberculoid granuloma response?

A

bovis
tuberculosis
marinum

359
Q

Which type of granuloma response has abundant organisms and which has sparse?

A

Nodular: sparse
Diffuse: abundant

360
Q

Diffuse/lepromatous granulomas are mediated by what T cell response?

A

Th2

361
Q

What Mycobacterium species are associated with a diffuse granuloma response?

A

lepra

avium ssp. paratuberculosis

362
Q

What are the acute phase proteins?

A 
C-reactive protein
Fibrinogen
Serum amyloid A (SAA)
Hepcidin
Albumin
a1-acid glycoprotein, haptoglobin, mannose-binding protein, a1-antitrypsin, C3, C4
363
Q

What induces production of fibrinogen?

A

IL-6

364
Q

What induces production of serum amyloid A (SADD)?

A

IL-1, IL-6, TNF

365
Q

Chronic elevation of what acute phase protein results in decreased iron availability and anemia of chronic disease?

A

Hepcidin

366
Q

What is the acute phase protein that decreases in inflammation?

A

Albumin

367
Q

What are the permanent cell types?

A

Most neurons

Cardiac myocytes

368
Q

What are the stable cell types?

A

Parenchyma of most solid tissues: liver, kidney, pancreas
Endothelial cells
Fibroblasts
Smooth muscle cells

369
Q

What are the labile cell types?

A

Hematopoietic tissues
Surface epithelium of skin, oral cavity, genitals
Cuboidal epithelium of ducts draining exocrine organs (salivary, pancreas, biliary)
Columnar epithelium of GI, uterus
Urinary transitional epithelium

370
Q

What cell cycle stage are stable cells in?

A

G0 (quiescent)

371
Q

Which molecule initiates vascular sprouting during angiogenesis?

A

VEGF (esp. A)

372
Q

Which molecules stabilize newly formed blood vessels during angiogenesis?

A

Angiopoietins 1 and 2 (Ang1 and Ang2)

373
Q

Which molecules recruit smooth muscle cells during angiogenesis?

A

PDGF

Ang1 and Ang2

374
Q

Which molecule suppresses endothelial proliferation and migration and enhances ECM protein production during angiogenesis?

A

TGF-B

375
Q

Which molecule regulates sprouting and branching?

A

Notch

376
Q

What molecule does Notch cross-talk with?

A

VEGF

377
Q

What MMPs are the interstitial collagenases?

A

1, 2, 3

378
Q

What MMPs are the gelatinases?

A

2, 9

379
Q

What MMPs are the stromolysins?

A

3, 10, 11

380
Q

What do the interstitial collagenases degrade?

A

Fibrillar collagen

381
Q

What do the gelatinases degrade?

A

Amorphous collagen

Fibronectin

382
Q

What do the stromelysins degrade?

A

Amorphous collagen
Fibronectin
Proteoglycans
Laminin

383
Q

What cells produce MMP1?

A

Fibroblasts

384
Q

What cells produce MMP2?

A

Fibroblasts

Endothelial cells

385
Q

What cells produce MMP3?

A

Fibroblasts

Endothelial cells

386
Q

What cells produce MMP9?

A

Endothelial cells
Macrophages
Neutrophils
Pericytes

387
Q

What cells produce MMP11?

A

Fibroblasts

388
Q

What cells produce MMP12?

A

Macrophages

389
Q

What cells produce MMP14?

A

Fibroblasts

390
Q

What MMPS do fibroblasts produce?

A

1, 2, 3, 11, 14

391
Q

What MMPS do endothelial cells produce?

A

2, 3, 9

392
Q

What MMPS do macrophages produce?

A

9, 12

393
Q

What MMPS do neutrophils produce?

A

9

394
Q

What MMPS do pericytes produce?

A

9

395
Q

What MMPS do tumor cells produce?

A

1, 3, 7, 9, 13

396
Q

What molecule inhibits MMPs

A

Tissue inhibitors of metalloproteinases (TIMPs)

397
Q

What is a cofactor for MMPs?

A

Zinc

398
Q

What degrades the ECM other than MMPs?

A 
ADAM (zinc proteinase)
Cathepsin G
tPA
uPA
Lysosomal enzymes: hyaluronidases, heparinases, galactocidases
399
Q

What activates Rac-1 during the transmigration process?

A

VCAM-1 clustering

400
Q

What are the effects of Rac-1 activation?

A

Production of ROS –> activates protein kinase C-a –> phosphorylates VE-cadherin –> loosening of intercellular adhesion

401
Q

What organ system is IFN-E produced?

A

Female reproductive tract

402
Q

Leukocytes produce all chemokine groups EXCEPT____, which is produced by ____ and results in______.

A

CX3CL (fractalkine)
Endothelial cells
Monocyte chemotaxis

403
Q

The binding of chemokines to atypical chemokine receptors leads to what?

A

Chemokine degradation

404
Q

CXCL13 (also known as ____), is produced by B cells and binds which receptor?

A

BCA-1/BCL-1 (B lymphocyte attracting chemokine)

CXCR5

405
Q

What cells produce IL-1 receptor antagonists?

A

Macrophages
Hepatocytes
Keratinocytes

406
Q

What is another name for C1 INH?

A

Serpin

407
Q

What molecules deactivate macrophages?

A

IL-10
CD47
IFN-a
GM-CSF

408
Q

Which mediator inhibits epithelial differentiation?

A

NF-kB

409
Q

Which transcription factors are involved in epithelial differentiation?

A

GATA6
TTF1
HNF-B
HFH-4

410
Q

What cyclooxygenase does TxA2 arise from?

A

COX-1

Phase I (10 decks)

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