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Gen Path > Inflammation > Flashcards

Inflammation Flashcards

1
Q

Mast Cells - production location and influence

A

Bone marrow; IL-3

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2
Q

Mast cells - location and lifespan

A

Mucosal and connective tissue; 4-12 wks

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3
Q

Mast cells - degranulation process

A

Cross-linking of IgE-bound FcERI in response to antigen

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4
Q

Mast cells - stored mediators and synthesized mediators

A

Vasoactive amines (histamine), TNF-a, proteoglycans, proteases ;
Cytokines, chemokines, LTC4, PGD2, PAF

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5
Q

Basophils - production location and influence

A

Bone marrow; IL-3

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6
Q

Basophils - location and lifespan

A

Bloodstream; several days in tissue

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7
Q

Basophils - granule contents

A

Histamine, cytokines (IL-4, 13), sulfated mucopolysaccharides

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8
Q

Basophils - function

A

Type I hypersensitivity reactions, rejection of parasites, promotion of lipid metabolism

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9
Q

Neutrophils - production location and influence

A

Bone marrow; TNF, IL-1, GM-CSF, G-CSF, IL-3

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10
Q

Neutrophils - location and lifespan

A

Bloodstream; 1-4d

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11
Q

Neutrophils - function

A

-Triggers HIF1a –> induces transcription of genes responsible for phagocytosis, inhibition of apoptosis, release of granule contents and cytokines, and iNOS
-Phagocytosis - opsonized (IgG, C3b), phagosomal-lysosomal fusion, resp burst
-Granule secretion

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12
Q

Neutrophils - granule contents

A

•Tertiary: *cathepsins
•Secondary (specific): *NADPH oxidase, defensins, lactoferrin, lysozyme, cathelicidin
•Primary (azurophilic): *myeloperoxidase, defensins, lysozyme, elastase

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13
Q

NETs composition

A

[Neutrophil extracellular traps]
Extruded DNA, granule components, histones (antimicrobial), elastase

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14
Q

Mononuclear phagocyte - types

A

-Resident tissue macs (free/fixed) - self-replenishing, resident
-Macs derived from monos - recruited (arrive 12-48h), short-lived

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15
Q

Mononuclear phagocyte - production influence by?

A

IL-1/3/6, SCF, GM-CSF, M-CSF

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16
Q

Mononuclear phagocyte - contents

A

Lysosomes

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17
Q

Mononuclear phagocyte - regulation

A

Regulate inflamm response: TNFa, IL-1, IL-6, lipid mediators

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18
Q

Mononuclear M1 phagocyte - activated by?

A

IFN-y

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19
Q

Eosinophils - production mediated by?

A

IL-5

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20
Q

Eosinophils - recruitment mediated by?

A

IL-4/5/13, eotaxin (CCL-11, RANTES (CCL5), C5a

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21
Q

Eosinophils - granules

A

Specific granules: major basic protein, eosinophil cationic protein, eosinophil-derived neuroprotein, eosinophil peroxidase

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22
Q

Eosinophils - function

A

allergic and parasitic disease

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23
Q

NK cells - function

A

Kill infected cells that have lost MHC class I by secreting cytotoxic perforin and granzymes

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24
Q

NK cells - types and secretion

A

Type I –> IFN-y
Type II –> IL-4/5/13

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25
Q

NK cells - differentiation, activation, and apoptosis regulated by?

A

IL-21

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26
Q

NK-T cells - markers

A

CD3+ (T lymphs) that have both T and NK cell properties

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27
Q

NK-T cells - what do they recognize?

A

CD1d (present self and foreign lipids and glycolipids)

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28
Q

NK-T cells - secretion

A

IFN-y, IL-4, GM-CSF

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29
Q

What are Intraepithelial lymphocytes (IEL)

A

T lymphs in epidermis, mucosal epithelia

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30
Q

Intraepithelial lymphocytes (IEL) - expression

A

CD8+, mostly gamma/delta T cells

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31
Q

B-1 cells - location, production

A

Peritoneal cavity and marginal zones of spleen; produce IgM specific for polysaccharide and lipid antigens

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32
Q

B-1 cells - immunity response (innate vs adaptive)

A

The only B cell part of innate response

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33
Q

Platelets - granules

A

Alpha: coag/growth factors, plt adhesion and repair proteins
Dense: adenine nucleotides, Ca, Mg, serotonin
Lysosomes: hydrolases

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34
Q

Cellular mediators of acute inflammation - preformed and newly synthesized

A

Preformed: histamine, serotonin, lysosomal enzymes
Newly synthesized: prostaglandins, leukotrienes, plt-activating factors, activated oxygen species, NO, cytokines

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35
Q

Liver mediators of acute inflammation

A

Factor XII, complement components

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36
Q

Histamine (H1, H2, and H4) - receptors and location

A

•H1 - smooth muscle cells (& leukocytes)
•H2 - gastric mucosa
•H4 - leukocytes, mast cells, dendritic cells, T lymphs

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37
Q

Serotonin - where found

A

Rodent mast cells, mammalian plts, neuroendocrine cells of the GIT, in the CNS

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38
Q

Serotonin - function

A

Inc vascular permeability, vasoconstriction

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39
Q

Arachidonic acid - released by and act through which receptor?

A

Phospholipase A2; G-protein coupled receptors

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40
Q

Prostaglandins - types

A

COX, PGI2, TXA2, PGD2, PGE2, PGF2a

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41
Q

Cyclooxygenases - types, location, +/- function

A

-COX1: constitutive and induced in almost all cells; homeostatic functions
-COX2: WBCs, endothelium, synovial fibroblasts; induced during inflamm
-COX3: splice variant of COX1; expressed in brain

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42
Q

Leukotrienes - types

A

-LTB4 - potent recruiter/activator of neuts and macs
-LTC4 - intense vasoconstriction, bronchospasm, vascular permeability
-LTD4: “
-LTE4: “

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43
Q

Lipoxins - functions

A

Stimulate mac adhesion, inhibit neut adhesion to endothelium and chemotaxis

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44
Q

Platelet activating factor (PAF) - functions

A

Plt aggregation, vasoconstriction/bronchoconstriction (at high doses; low doses opposite), inc WBC adhesion and chemotaxis and degranulation and oxidative burst, boosts synthesis of other mediators

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45
Q

iNOS - induced by?

A

IFN-y

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46
Q

TNF/IL-1 - has effects on what?

A

Vascular permeability
Leukocytes
Fibroblasts

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47
Q

TNF/IL-1 - effects on fibroblasts

A

-Proliferation
-Inc collagen synthesis

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48
Q

TNF/IL-1 - effects on leukocytes

A

-Activation
-Production of cytokines

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49
Q

TNF/IL-1 - effects on vasculature

A

-Inc expression of leukocyte adhesion molecules
-Production of IL-1, chemokines
-Inc procoag and dec anticoag activity

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50
Q

IL-1 - produced by

A

Macs, neuts, epithelial, endothelial cells

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51
Q

IL-12 - produced by what in response to what?

A

Activated macs and DCs in response to infxn

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52
Q

IL-12 - induces what?

A

Th1 response (cell-mediated immunity)

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53
Q

IL-6 - produced by what in response to what?

A

Macs, endothelial cells, fibroblasts in response to microbes

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54
Q

IL-6 - functions

A

Stimulates synthesis of APP, production of neuts, growth of antibody-producing B cells

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55
Q

IL-10 - functions

A

Anti-inflamm via inhibition of activated macs/DCs (return to resting state)

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56
Q

Chemokines - structural groups and what secretes them

A

-C: lymphs
-CC: eos, lymphs
-CXC: macs, endothelial cells
-CX3C: monos, T cells

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57
Q

Complement cascade - pathways

A

-Classical: fixation of C1 to IgG or IgM bound to antigen
-Alternative: triggered by microbial surface molecules in absence of antibody
-Lectin: MBL/ficolins bind carbs on microbes

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58
Q

C5a effects

A

Anaphylotoxins (mast cell degranulation –> vasodilation and inc vascular permeability), recruit PMNs

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59
Q

C3a effects

A

Anaphylotoxins (mast cell degranulation –> vasodilation and inc vascular permeability), recruit PMNs

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60
Q

Complement factor that promotes phagocytosis (opsonin)

A

C3b

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61
Q

C5b-9

A

MAC –> microbial lysis

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62
Q

Regulators of complement

A

C1 inhibitor, decay accelerating factor (DAF), CD59

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63
Q

DAF

A

[Decay accelerating factor]
Prevents formation of C3 convertases

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64
Q

CD59

A

Inhibits formation of MAC

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65
Q

PARs - functions

A

[Protease-activated receptors]
Mobilization of P-selectin and endothelial adhesion molecules, production of cytokines, induction of COX-2, production of PAF and NO, changes in endothelial shape

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66
Q

Bradykinin - functions

A

Inc vascular permeability, contraction of smooth muscle, vasodilation, pain, stimulates PLA2

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67
Q

Tachykinins - functions

A

Vasodilation, vascular permeability, smooth muscle contraction, mucus secretion, pain, chemotaxis and activation/degran of mast cells and basos and eos, stimulates vomiting center

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68
Q

Plasmin - functions

A

Cleaves fibrin to release FSPs/FDPs, cleaves C3 to C3a, activates HF [Hageman Factor]

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69
Q

FSPs - functions

A

[Fibrin split products]
Vascular permeability, recruit neuts

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70
Q

High mobility group box protein-1 - functions

A

Mediator of endotoxemia, sepsis, cancer, pain

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71
Q

Pain receptor

72
Q

Anti-inflamm cytokines

A

TGF-B, IL-10

73
Q

Anti-inflamm lipid mediators

A

Resolvins, protectins

74
Q

Septicemia - stages/types

A

-Septic shock - gram (+) or gram (-)
-Endotoxic shock - gram (-) LPS
-SIRS - “cytokine storm” –> survivors inc risk for CARS [compensatory anti-inflamm response syndrome]
-MODS [multiple organ dysfunction syndrome] - irreversible stage

75
Q

Granulomatous inflamm vs. granuloma vs. caseous granuloma

A

Granulomatous inflamm = infiltration by epithelioid macs
Granuloma = macs organized into focal or multifocal structure
Caseous granuloma = caseous necrosis of granuloma center

76
Q

Tuberculoid granuloma - bias

A

TH1 biased

77
Q

Lepromatous granulomatous inflamm - bias

A

TH2 biased; ex. Johne’s disease

78
Q

Eosinophilic granulomas - bias

A

TH2 directed

79
Q

Th - type: associated cytokine: transcriptional activator: outcome, pathogen/target

A

-Th1: IFNy: T-beta: IFNy: intracellular pathogens
-Th2: IL-4: GATA3: IL4/5/13: parasites
-Th17: IL-21: RORs: IL17/17F/22/21: extracellular pathogens
-Treg: TGF-B: Foxp3: TGF-B, IL10: autoimmunity

80
Q

Activated macs - types and functions

A

Classic: microbicidal actions and pathologic inflamm
Alternate: anti-inflamm and wound repair/fibrosis

81
Q

Dendritic cells - types and functions

A

-Immature = CD34+ –> mature after taking up antigen
-Mature = CCR7+ –> antigen-presenting to activate naïve T cells

82
Q

Histamine - source and action

A

Source: mast cells, basophils, platelets
Action: vasodilation, inc vascular permeability, bronchoconstriction, smooth muscle contraction, pain/itching, tachycardia, neural/vagal reflexes, eosinophil chemotaxis, endothelial activation

83
Q

Prostaglandins - source and action

A

Source: mast cells, leukocytes
Action: vasodilation, pain, fever

84
Q

Leukotrienes - source and action

A

Source: mast cells, leukocytes
Action: inc vascular permeability, chemotaxis, leukocyte adhesion and activation

85
Q

TNFa, IL1, IL6 - source and action

A

Source: macs, endothelial cells, mast cells
Action: local = endothelial activation (expression of adhesion molecules); systemic = fever, metabolic abnormalities, hypotension (shock)

86
Q

Chemokines - source and action

A

Source: leukocytes, activated macs
Action: chemotaxis, leukocyte activation

87
Q

Platelet activating factor - source and action

A

Source: leukocytes, mast cells
Action: vasodilation, inc vascular permeability, leukocyte adhesion, chemotaxis, degranulation, oxidative burst

88
Q

Complement - source and action

A

Source: plasma (produced in liver)
Action: leukocyte chemotaxis and activation, direct target killing (MAC), vasodilation (mast cell stimulation)

89
Q

Kinins - source and action

A

Source: plasma (produced in liver)
Action: inc vascular permeability, smooth muscle contraction, vasodilation, pain

90
Q

Anaphylotoxins

A

C3a and C5a

91
Q

Vasodilation mediators

A

NO, bradykinin, LTB4, histamine, and prostaglandins PGI2, PGE1, PGE2, PGD2

92
Q

Inc vascular permeability mediators

A

Vasoactive amines (histamine, substance P, bradykinin), complement factors C5a and C3a, fibrinopeptides and fibrin breakdown products, PGE2, leukotrienes LTB/C/D/E4, PAF, IL1, TNF

93
Q

Smooth muscle contraction mediators

A

Histamine, serotonin, C3a, bradykinin, PAF, LTD4

94
Q

Fever mediators

A

IL1, TNF, IL6, PGE2

95
Q

Vasoconstrictive eicosanoids

A

Thromboxane A2, leukotrienes C4, D4, E4

96
Q

Inc vascular permeability eicosanoids

A

Leukotrienes C4, D4, E4

97
Q

Chemotactic and leukocyte adhesion eicosanoids

A

Leukotrienes B4, HETE

98
Q

Prostacyclin effects

A

Vasodilation, inhibits platelet aggregation

99
Q

Thromboxane A2 effects

A

Vasoconstriction, promotes platelet aggregation

100
Q

PGD2 and PGE2 effects

A

Vasodilation, inc vascular permeability, leukocyte chemotaxis (PGD2)

101
Q

HETE effect

A

Chemotaxis

102
Q

LTC/D/E4 effects

A

Bronchospasm, inc vascular permeability

103
Q

Lipoxins LXA4 and LXB4 effects

A

Inhibits neutrophil adhesion and chemotaxis

104
Q

Chemokine receptor type

105
Q

MyD88 independent signaling

A

TLR3 and TLR4

106
Q

Cell membrane surface PRRs

A

TLR 1, 2, 4, 5, 6, 11 and IL-1

107
Q

Endosome PRRs

A

TLR 3, 7-9

108
Q

Cytoplasmic PRRs

A

NOD, RIG-1

109
Q

Bacterial lipoprotein PRR

A

TLR1, 2, 6

110
Q

LPS PRR

111
Q

Flagellum PRR

112
Q

Bacterial ribosomal RNA PRR

113
Q

DNA PRR

114
Q

dsRNA PRR

115
Q

ssRNA PRR

A

TLR7, 8, RIG-1, MDA5

116
Q

Gram negative bacteria PRR

A

NOD1
NOD2
NLR family proteins

117
Q

Gram positive bacteria PRR

A

NLR family

118
Q

Inhibition of JAK

A

SOCS 1-3 and PTPs

119
Q

Inhibition of STAT (cytoplasmic vs. intranuclear)

A

CIS (cytoplasmic) and PIAS (intranuclear)

120
Q

Complement system classical pathway activation

A

Fixation of C1 to antibody (IgM or IgG) bound to antigen

121
Q

Complement system alternative pathway activation

A

Microbial surface molecules and other substances in the absence of antibody

122
Q

Complement system lectin pathway activation

A

Fixation of C1 to plasma mannose-binding lectins, which bind mannose residues on microbial surfaces

123
Q

Complement Anaphylotoxins

A

C3a and C5a

124
Q

Formation of MAC requires which complement proteins?

125
Q

Waste disposal complement protein

126
Q

Actions of C5a

A

Anaphylotoxin (release of histamine from mast cells), chemotactic for granulocytes and monos, activates lipoxygenase pathway in neuts and monos (release of inflamm cytokines)

127
Q

Complement regulatory proteins

A

•C1 INH - blocks C1 activation
•Decay accelerating factor (DAF) - prevents C3 convertase
•CD59 - blocks MAC formation
•Complement factor H - inhibits alternative pathway by destruction of C3b and turnover of C3 convertase

128
Q

Platelet activating factor (PAF) actions

A

At high concentrations: platelet aggregation, vasoconstriction, bronchoconstriction, mast cell release of serotonin and histamine

129
Q

Kinin action

A

Formation of bradykinin

130
Q

Bradykinin functions

A

*Inc vascular permeability, smooth muscle contraction, *vasodilation, *pain, stimulation of phospholipase A2, hypotension, bronchoconstriction

131
Q

Substance P functions

A

Pain signals, blood pressure regulation, hormone secretion, inc vascular permeability, induce degranulation of mast cells and basos and eos

132
Q

Macrophage classical activation and function

A

•Microbial pathogens (TLR ligands) and IFN-gamma produced in Th1 immune responses by Th1 lymphs and NK lymphs
•Produce NO and ROS - microbe destruction and inflamm promotion
•Secrete IL1, 12, 23, chemokines - inflamm

133
Q

Macrophage alternative pathway activation and function

A

•Induced by IL4 and IL13, produced in Th2 immune responses by Th2 lymphs and granulocytes
•Secrete growth factors, TGF-B - tissue repair and fibrosis
•Secrete IL10, TGF-B - anti-inflamm

134
Q

TH1 cells - driven by, cytokines secreted, important disease state

A

•IL12, IFN-gamma, IL18, IL23, IL27
•IFN-gamma
•bacteria and viruses

135
Q

TH2 cells - driven by, cytokines secreted, important disease state

A

•IL4, 5, 9, 10, 13, 17
•IL4, 5, 10, 13
•helminthic and allergic diseases, foreign bodies or endogenous antigens

136
Q

TH17 cells - driven by, cytokines secreted, important disease state

A

•TGF-B, IL6, IL23
•IL17 - recruits neuts and monos
•autoimmune diseases

137
Q

Nodular (tuberculoid) granuloma type of bias and inciting organism examples

A

Th1
M. bovis or M. tuberculosis

138
Q

Diffuse (lepromatous) granuloma type of bias and inciting organism examples

A

Th2
M. avium subsp paratuberculosis (Johne’s Disease) or M. leprae

139
Q

Transcytosis is upregulated by what?

140
Q

Paracellular transport (b/w endothelial cells) of leukocytes is regulated by what?

A

Histamine and NO

141
Q

The immediate transient response in acute inflammation is characterized by what and mediated by what?

A

•Endothelial cell retraction following vasodilation
•Via histamine, most importantly, some of which is in endothelial cells

142
Q

Mediators of cytoskeletal reorganization (phase 2) of acute inflammation

A

IL1, IL6, TNF-a

143
Q

Leukocyte migration is mediated (in the leukocyte adhesion cascade) by what?

A

PECAM1 (CD31)

144
Q

L-selectin binds what?
E-selectin binds what?
P-selectin binds what?

A

L: Endothelial glycoproteins (Sialyl Lew X)
E and P: WBC glycoproteins (Sialyl Lew X)

145
Q

What do Weibel-Palade bodies contain?

A

•Preformed: P-selectin, vWF
•Upregulated (has to be created): E-selectin
•IL-8

146
Q

Rolling is mediated by what?

147
Q

Where is GlyCAM-1 expressed and what does it bind?

A

High endothelial venules, lymphoid tissue
L-selectin

148
Q

Where is MadCAM-1 expressed and what does it bind?

A

MALT
Binds L-selectin and integrins

149
Q

Heparan sulfate function

A

Binds anti-thrombin III (AT-III) which helps it function - inhibits thrombin

150
Q

Thrombomodulin function

A

Changes thrombin’s specificity to protein C, promoting anti-thrombotic status

151
Q

GPCR protein receptor group and give examples

A

Chemokines - examples are histamine, C3a, C5a

152
Q

Primary neutrophil cytokine

153
Q

Primary eosinophil cytokine

154
Q

NF-kB expression results in what?

A

Inflammation!
IL1, 6, TNF-a, IL-12
IL-8, IL-18, RANTES

155
Q

Integrin Adhesion Complexes bind what and recruit which kinases?

A

•Talin, Vinculin
•FAK, Src

156
Q

Leukocyte adhesion is mediated by what?

157
Q

What mediates the switch from selectins to integrins?

A

ADAM17 (sheddase)

158
Q

Leukocyte adhesion deficiency is characterized by a mutation in what?

A

CD18 (integrin beta 2)

159
Q

LFA1 is found on which cells and binds to what and is expressed where?

A

Neuts, monos, T cells
ICAM1, ICAM2
Endothelial cells

160
Q

MAC1 is found on which cells and binds to what and is expressed where?

A

Monos, DCs, PMNs
ICAM1, ICAM2
Endothelium

161
Q

VLA1 is found on which cells and binds to what and is expressed where?

A

Monos, T cells
VCAM1
Endothelium

162
Q

PECAM1 is expressed on which cells?

A

Platelets, endothelial cells, leukocytes

163
Q

Function of JAMs

A

Make up normal endothelial-endothelial tight junctions (along with PECAM)

164
Q

What receptor retains PMNs in the bone marrow?
What receptor releases PMNs in the bone marrow?
What modulates these receptors?

A

CXCR4
CXCR2
G-CSF

165
Q

Exogenous activators of neutrophils

A

N-f-Met, unmethylated CpG, dsRNA

166
Q

End point of mannose-binding lectin complement pathway

A

Cleavage of C4 and C2 (which cleave C3)
Direct cleaving of C3

167
Q

NADPH oxidase function and location

A

Creates O2• (superoxide) which eventually becomes H2O2
Found in secondary granules of neuts

168
Q

Fenton reaction endpoint

A

Generates iron to be used to create hydroxyl free radical OH-

169
Q

MPO function and location

A

Forms hypochlorite (HOCl) aka bleach
Found in primary granules of neuts

170
Q

Function of iNOS

A

Utilizes superoxide O2- and NO to create ONOO-

171
Q

Marker of NET formation

A

Justine citrullination

172
Q

Phagocytic cytoplasts

A

Neuts that have secreted their nucleus (NETs) but still retain their cytoplasm and granules

173
Q

Most abundant protein in the cytosol of neutrophils

A

Calprotectin

174
Q

What makes macrophages stay in tissue?

A

Macrophage inhibitory factor

175
Q

Annexin-1 function

A

Anti-inflammatory

Gen Path (8 decks)

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