Inflammation Flashcards
1
Q
Mast Cells - production location and influence
A
Bone marrow; IL-3
2
Q
Mast cells - location and lifespan
A
Mucosal and connective tissue; 4-12 wks
3
Q
Mast cells - degranulation process
A
Cross-linking of IgE-bound FcERI in response to antigen
4
Q
Mast cells - stored mediators and synthesized mediators
A
Vasoactive amines (histamine), TNF-a, proteoglycans, proteases ;
Cytokines, chemokines, LTC4, PGD2, PAF
5
Q
Basophils - production location and influence
A
Bone marrow; IL-3
6
Q
Basophils - location and lifespan
A
Bloodstream; several days in tissue
7
Q
Basophils - granule contents
A
Histamine, cytokines (IL-4, 13), sulfated mucopolysaccharides
8
Q
Basophils - function
A
Type I hypersensitivity reactions, rejection of parasites, promotion of lipid metabolism
9
Q
Neutrophils - production location and influence
A
Bone marrow; TNF, IL-1, GM-CSF, G-CSF, IL-3
10
Q
Neutrophils - location and lifespan
A
Bloodstream; 1-4d
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
12
Q
Neutrophils - granule contents
A
•Tertiary: *cathepsins
•Secondary (specific): *NADPH oxidase, defensins, lactoferrin, lysozyme, cathelicidin
•Primary (azurophilic): *myeloperoxidase, defensins, lysozyme, elastase
13
Q
NETs composition
A
[Neutrophil extracellular traps]
Extruded DNA, granule components, histones (antimicrobial), elastase
14
Q
Mononuclear phagocyte - types
A
-Resident tissue macs (free/fixed) - self-replenishing, resident
-Macs derived from monos - recruited (arrive 12-48h), short-lived
15
Q
Mononuclear phagocyte - production influence by?
A
IL-1/3/6, SCF, GM-CSF, M-CSF
16
Q
Mononuclear phagocyte - contents
A
Lysosomes
17
Q
Mononuclear phagocyte - regulation
A
Regulate inflamm response: TNFa, IL-1, IL-6, lipid mediators
18
Q
Mononuclear M1 phagocyte - activated by?
A
IFN-y
19
Q
Eosinophils - production mediated by?
A
IL-5
20
Q
Eosinophils - recruitment mediated by?
A
IL-4/5/13, eotaxin (CCL-11, RANTES (CCL5), C5a
21
Q
Eosinophils - granules
A
Specific granules: major basic protein, eosinophil cationic protein, eosinophil-derived neuroprotein, eosinophil peroxidase
22
Q
Eosinophils - function
A
allergic and parasitic disease
23
Q
NK cells - function
A
Kill infected cells that have lost MHC class I by secreting cytotoxic perforin and granzymes
24
Q
NK cells - types and secretion
A
Type I –> IFN-y
Type II –> IL-4/5/13
25
NK cells - differentiation, activation, and apoptosis regulated by?
IL-21
26
NK-T cells - markers
CD3+ (T lymphs) that have both T and NK cell properties
27
NK-T cells - what do they recognize?
CD1d (present self and foreign lipids and glycolipids)
28
NK-T cells - secretion
IFN-y, IL-4, GM-CSF
29
What are Intraepithelial lymphocytes (IEL)
T lymphs in epidermis, mucosal epithelia
30
Intraepithelial lymphocytes (IEL) - expression
CD8+, mostly gamma/delta T cells
31
B-1 cells - location, production
Peritoneal cavity and marginal zones of spleen; produce IgM specific for polysaccharide and lipid antigens
32
B-1 cells - immunity response (innate vs adaptive)
The only B cell part of innate response
33
Platelets - granules
Alpha: coag/growth factors, plt adhesion and repair proteins
Dense: adenine nucleotides, Ca, Mg, serotonin
Lysosomes: hydrolases
34
Cellular mediators of acute inflammation - preformed and newly synthesized
Preformed: histamine, serotonin, lysosomal enzymes
Newly synthesized: prostaglandins, leukotrienes, plt-activating factors, activated oxygen species, NO, cytokines
35
Liver mediators of acute inflammation
Factor XII, complement components
36
Histamine (H1, H2, and H4) - receptors and location
•H1 - smooth muscle cells (& leukocytes)
•H2 - gastric mucosa
•H4 - leukocytes, mast cells, dendritic cells, T lymphs
37
Serotonin - where found
Rodent mast cells, mammalian plts, neuroendocrine cells of the GIT, in the CNS
38
Serotonin - function
Inc vascular permeability, vasoconstriction
39
Arachidonic acid - released by and act through which receptor?
Phospholipase A2; G-protein coupled receptors
40
Prostaglandins - types
COX, PGI2, TXA2, PGD2, PGE2, PGF2a
41
Cyclooxygenases - types, location, +/- function
-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
42
Leukotrienes - types
-LTB4 - potent recruiter/activator of neuts and macs
-LTC4 - intense vasoconstriction, bronchospasm, vascular permeability
-LTD4: "
-LTE4: "
43
Lipoxins - functions
Stimulate mac adhesion, inhibit neut adhesion to endothelium and chemotaxis
44
Platelet activating factor (PAF) - functions
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
45
iNOS - induced by?
IFN-y
46
TNF/IL-1 - has effects on what?
Vascular permeability
Leukocytes
Fibroblasts
47
TNF/IL-1 - effects on fibroblasts
-Proliferation
-Inc collagen synthesis
48
TNF/IL-1 - effects on leukocytes
-Activation
-Production of cytokines
49
TNF/IL-1 - effects on vasculature
-Inc expression of leukocyte adhesion molecules
-Production of IL-1, chemokines
-Inc procoag and dec anticoag activity
50
IL-1 - produced by
Macs, neuts, epithelial, endothelial cells
51
IL-12 - produced by what in response to what?
Activated macs and DCs in response to infxn
52
IL-12 - induces what?
Th1 response (cell-mediated immunity)
53
IL-6 - produced by what in response to what?
Macs, endothelial cells, fibroblasts in response to microbes
54
IL-6 - functions
Stimulates synthesis of APP, production of neuts, growth of antibody-producing B cells
55
IL-10 - functions
Anti-inflamm via inhibition of activated macs/DCs (return to resting state)
56
Chemokines - structural groups and what secretes them
-C: lymphs
-CC: eos, lymphs
-CXC: macs, endothelial cells
-CX3C: monos, T cells
57
Complement cascade - pathways
-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
58
C5a effects
Anaphylotoxins (mast cell degranulation --> vasodilation and inc vascular permeability), recruit PMNs
59
C3a effects
Anaphylotoxins (mast cell degranulation --> vasodilation and inc vascular permeability), recruit PMNs
60
Complement factor that promotes phagocytosis (opsonin)
C3b
61
C5b-9
MAC --> microbial lysis
62
Regulators of complement
C1 inhibitor, decay accelerating factor (DAF), CD59
63
DAF
[Decay accelerating factor]
Prevents formation of C3 convertases
64
CD59
Inhibits formation of MAC
65
PARs - functions
[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
66
Bradykinin - functions
Inc vascular permeability, contraction of smooth muscle, vasodilation, pain, stimulates PLA2
67
Tachykinins - functions
Vasodilation, vascular permeability, smooth muscle contraction, mucus secretion, pain, chemotaxis and activation/degran of mast cells and basos and eos, stimulates vomiting center
68
Plasmin - functions
Cleaves fibrin to release FSPs/FDPs, cleaves C3 to C3a, activates HF [Hageman Factor]
69
FSPs - functions
[Fibrin split products]
Vascular permeability, recruit neuts
70
High mobility group box protein-1 - functions
Mediator of endotoxemia, sepsis, cancer, pain
71
Pain receptor
PGE2
72
Anti-inflamm cytokines
TGF-B, IL-10
73
Anti-inflamm lipid mediators
Resolvins, protectins
74
Septicemia - stages/types
-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
Granulomatous inflamm vs. granuloma vs. caseous granuloma
Granulomatous inflamm = infiltration by epithelioid macs
Granuloma = macs organized into focal or multifocal structure
Caseous granuloma = caseous necrosis of granuloma center
76
Tuberculoid granuloma - bias
TH1 biased
77
Lepromatous granulomatous inflamm - bias
TH2 biased; ex. Johne's disease
78
Eosinophilic granulomas - bias
TH2 directed
79
Th - type: associated cytokine: transcriptional activator: outcome, pathogen/target
-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
Activated macs - types and functions
Classic: microbicidal actions and pathologic inflamm
Alternate: anti-inflamm and wound repair/fibrosis
81
Dendritic cells - types and functions
-Immature = CD34+ --> mature after taking up antigen
-Mature = CCR7+ --> antigen-presenting to activate naïve T cells
82
Histamine - source and action
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
Prostaglandins - source and action
Source: mast cells, leukocytes
Action: vasodilation, pain, fever
84
Leukotrienes - source and action
Source: mast cells, leukocytes
Action: inc vascular permeability, chemotaxis, leukocyte adhesion and activation
85
TNFa, IL1, IL6 - source and action
Source: macs, endothelial cells, mast cells
Action: local = endothelial activation (expression of adhesion molecules); systemic = fever, metabolic abnormalities, hypotension (shock)
86
Chemokines - source and action
Source: leukocytes, activated macs
Action: chemotaxis, leukocyte activation
87
Platelet activating factor - source and action
Source: leukocytes, mast cells
Action: vasodilation, inc vascular permeability, leukocyte adhesion, chemotaxis, degranulation, oxidative burst
88
Complement - source and action
Source: plasma (produced in liver)
Action: leukocyte chemotaxis and activation, direct target killing (MAC), vasodilation (mast cell stimulation)
89
Kinins - source and action
Source: plasma (produced in liver)
Action: inc vascular permeability, smooth muscle contraction, vasodilation, pain
90
Anaphylotoxins
C3a and C5a
91
Vasodilation mediators
NO, bradykinin, LTB4, histamine, and prostaglandins PGI2, PGE1, PGE2, PGD2
92
Inc vascular permeability mediators
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
Smooth muscle contraction mediators
Histamine, serotonin, C3a, bradykinin, PAF, LTD4
94
Fever mediators
IL1, TNF, IL6, PGE2
95
Vasoconstrictive eicosanoids
Thromboxane A2, leukotrienes C4, D4, E4
96
Inc vascular permeability eicosanoids
Leukotrienes C4, D4, E4
97
Chemotactic and leukocyte adhesion eicosanoids
Leukotrienes B4, HETE
98
Prostacyclin effects
Vasodilation, inhibits platelet aggregation
99
Thromboxane A2 effects
Vasoconstriction, promotes platelet aggregation
100
PGD2 and PGE2 effects
Vasodilation, inc vascular permeability, leukocyte chemotaxis (PGD2)
101
HETE effect
Chemotaxis
102
LTC/D/E4 effects
Bronchospasm, inc vascular permeability
103
Lipoxins LXA4 and LXB4 effects
Inhibits neutrophil adhesion and chemotaxis
104
Chemokine receptor type
GPCR
105
MyD88 independent signaling
TLR3 and *TLR4*
106
Cell membrane surface PRRs
TLR 1, 2, 4, 5, 6, 11 and IL-1
107
Endosome PRRs
TLR 3, 7-9
108
Cytoplasmic PRRs
NOD, RIG-1
109
Bacterial lipoprotein PRR
TLR1, 2, 6
110
LPS PRR
TLR4
111
Flagellum PRR
TLR5
112
Bacterial ribosomal RNA PRR
TLR13
113
DNA PRR
TLR9
114
dsRNA PRR
TLR3
115
ssRNA PRR
TLR7, 8, RIG-1, MDA5
116
Gram negative bacteria PRR
NOD1
NOD2
NLR family proteins
117
Gram positive bacteria PRR
NLR family
118
Inhibition of JAK
SOCS 1-3 and PTPs
119
Inhibition of STAT (cytoplasmic vs. intranuclear)
CIS (cytoplasmic) and PIAS (intranuclear)
120
Complement system classical pathway activation
Fixation of C1 to antibody (IgM or IgG) bound to antigen
121
Complement system alternative pathway activation
Microbial surface molecules and other substances in the absence of antibody
122
Complement system lectin pathway activation
Fixation of C1 to plasma mannose-binding lectins, which bind mannose residues on microbial surfaces
123
Complement Anaphylotoxins
C3a and C5a
124
Formation of MAC requires which complement proteins?
C5b-9
125
Waste disposal complement protein
C1q
126
Actions of C5a
Anaphylotoxin (release of histamine from mast cells), chemotactic for granulocytes and monos, activates lipoxygenase pathway in neuts and monos (release of inflamm cytokines)
127
Complement regulatory proteins
•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
Platelet activating factor (PAF) actions
At high concentrations: platelet aggregation, vasoconstriction, bronchoconstriction, mast cell release of serotonin and histamine
129
Kinin action
Formation of bradykinin
130
Bradykinin functions
*Inc vascular permeability, smooth muscle contraction, *vasodilation, *pain, stimulation of phospholipase A2, hypotension, bronchoconstriction
131
Substance P functions
Pain signals, blood pressure regulation, hormone secretion, inc vascular permeability, induce degranulation of mast cells and basos and eos
132
Macrophage classical activation and function
•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
Macrophage alternative pathway activation and function
•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
TH1 cells - driven by, cytokines secreted, important disease state
•IL12, IFN-gamma, IL18, IL23, IL27
•IFN-gamma
•bacteria and viruses
135
TH2 cells - driven by, cytokines secreted, important disease state
•IL4, 5, 9, 10, 13, 17
•IL4, 5, 10, 13
•helminthic and allergic diseases, foreign bodies or endogenous antigens
136
TH17 cells - driven by, cytokines secreted, important disease state
•TGF-B, IL6, IL23
•IL17 - recruits neuts and monos
•autoimmune diseases
137
Nodular (tuberculoid) granuloma type of bias and inciting organism examples
Th1
M. bovis or M. tuberculosis
138
Diffuse (lepromatous) granuloma type of bias and inciting organism examples
Th2
M. avium subsp paratuberculosis (Johne’s Disease) or M. leprae
139
Transcytosis is upregulated by what?
VEGF
140
Paracellular transport (b/w endothelial cells) of leukocytes is regulated by what?
Histamine and NO
141
The immediate transient response in acute inflammation is characterized by what and mediated by what?
•Endothelial cell retraction following vasodilation
•Via histamine, most importantly, some of which is in endothelial cells
142
Mediators of cytoskeletal reorganization (phase 2) of acute inflammation
IL1, IL6, TNF-a
143
Leukocyte migration is mediated (in the leukocyte adhesion cascade) by what?
PECAM1 (CD31)
144
L-selectin binds what?
E-selectin binds what?
P-selectin binds what?
L: Endothelial glycoproteins (Sialyl Lew X)
E and P: WBC glycoproteins (Sialyl Lew X)
145
What do Weibel-Palade bodies contain?
•Preformed: P-selectin, vWF
•Upregulated (has to be created): E-selectin
•IL-8
146
Rolling is mediated by what?
Selectins
147
Where is GlyCAM-1 expressed and what does it bind?
High endothelial venules, lymphoid tissue
L-selectin
148
Where is MadCAM-1 expressed and what does it bind?
MALT
Binds L-selectin and integrins
149
Heparan sulfate function
Binds anti-thrombin III (AT-III) which helps it function - inhibits thrombin
150
Thrombomodulin function
Changes thrombin’s specificity to protein C, promoting anti-thrombotic status
151
GPCR protein receptor group and give examples
Chemokines - examples are histamine, C3a, C5a
152
Primary neutrophil cytokine
IL-8
153
Primary eosinophil cytokine
IL-5
154
NF-kB expression results in what?
Inflammation!
IL1, 6, TNF-a, IL-12
IL-8, IL-18, RANTES
155
Integrin Adhesion Complexes bind what and recruit which kinases?
•Talin, Vinculin
•FAK, Src
156
Leukocyte adhesion is mediated by what?
Integrins
157
What mediates the switch from selectins to integrins?
ADAM17 (sheddase)
158
Leukocyte adhesion deficiency is characterized by a mutation in what?
CD18 (integrin beta 2)
159
LFA1 is found on which cells and binds to what and is expressed where?
Neuts, monos, T cells
ICAM1, ICAM2
Endothelial cells
160
MAC1 is found on which cells and binds to what and is expressed where?
Monos, DCs, PMNs
ICAM1, ICAM2
Endothelium
161
VLA1 is found on which cells and binds to what and is expressed where?
Monos, T cells
VCAM1
Endothelium
162
PECAM1 is expressed on which cells?
Platelets, endothelial cells, leukocytes
163
Function of JAMs
Make up normal endothelial-endothelial tight junctions (along with PECAM)
164
What receptor retains PMNs in the bone marrow?
What receptor releases PMNs in the bone marrow?
What modulates these receptors?
CXCR4
CXCR2
G-CSF
165
Exogenous activators of neutrophils
N-f-Met, unmethylated CpG, dsRNA
166
End point of mannose-binding lectin complement pathway
Cleavage of C4 and C2 (which cleave C3)
Direct cleaving of C3
167
NADPH oxidase function and location
Creates O2• (superoxide) which eventually becomes H2O2
Found in secondary granules of neuts
168
Fenton reaction endpoint
Generates iron to be used to create hydroxyl free radical OH-
169
MPO function and location
Forms hypochlorite (HOCl) aka bleach
Found in primary granules of neuts
170
Function of iNOS
Utilizes superoxide O2- and NO to create ONOO-
171
Marker of NET formation
Justine citrullination
172
Phagocytic cytoplasts
Neuts that have secreted their nucleus (NETs) but still retain their cytoplasm and granules
173
Most abundant protein in the cytosol of neutrophils
Calprotectin
174
What makes macrophages stay in tissue?
Macrophage inhibitory factor
175
Annexin-1 function
Anti-inflammatory
