4 Inflammation and Its Mediators Flashcards
1
Q
Responsible for elimination of pathogens in subsequent phases of infection
A
Adaptive immune system
2
Q
Responsible for maintenance of immunological tolerance
A
Adaptive immune system
3
Q
T/F Adaptive immunity exists only in vertebrates
A
T
4
Q
Cells that recognize altered self
A
NK cells
5
Q
Neutrophilic granules that contain lysozyme, elastase, and collagenase
A
Specific granules
6
Q
Lysosomes that contain enzymes and microbicidal substances found in the cytoplasm of neutrophils
A
Azurophilic granules
7
Q
Most prevalent cell type in the early phases of antimicrobial response
A
Neutrophils
8
Q
Dominant effector cells in the later stages of inflammation
A
Recruited monocytes-macrophages
9
Q
Within ___ days, neutrophils are almost completely replaced by monocytes-macrophages
A
1-2
10
Q
T/F PAMPs are essential for microbial survival
A
T
11
Q
PRR: Characterized by extracellular leucine-rich repeat (LRR) domain and intracellular Toll IL-1 receptor (T1R) domain
A
TLR
12
Q
Number of TLRs identified in humans
A
13
13
Q
TLR: Expressed at the cell surface and mainly recognize bacterial products unique to bacteria
A
TLR 1,2,4,5,6,10
14
Q
TLR: Located almost exclusively in intracellular compartments, including endosomes and lysosomes
A
TLR 3,7,8,9,11,12,13
15
Q
PAMP-origin-PRR-main effector function: LPS
A
G-bacteria; TLR4, CD14; macrophage activation
16
Q
PAMP-origin-PRR-main effector function: Unmethylated CpG nucleotides
A
Bacterial DNA; TLR9; macrophage, B-cell, plasmacytoid cell activation
17
Q
PAMP-origin-PRR-main effector function: Terminal mannose residues
A
Microbial glycoprotein and glycolipids;
1) Macrophage mannose receptor; phagocytosis
2) Plasma MBL; complement activation opsonization
18
Q
PAMP-origin-PRR-main effector function: LPS, dsRNA
A
Bacteria, viruses; Macrophage scavenger receptor; Phagocytosis
19
Q
PAMP-origin-PRR-main effector function: Zymosan
A
Fungi; TLR2, Dectin-1; Macrophage activation
20
Q
PAMP-origin-PRR-main effector function: dsRNA
A
Viral; TLR3, RIG-I; IFN Type I production
21
Q
PAMP-origin-PRR-main effector function: ssRNA
A
Viral; TLR7/8, MDA5; IFN Type I production
22
Q
PAMP-origin-PRR-main effector function: N-formylmethionine residues
A
Bacteria; Chemokine receptors; Neutrophil and macrophage activation and migration
23
Q
PAMP-origin-PRR-main effector function: MDP
A
G+ and G- bacteria; NOD2, NALP1; Macrophage activation
24
Q
TLR located in both cell surface and endolysosomal compartment
A
TLR4
25
TLR-Ligand: TLR1
Lipopeptides
26
TLR-Ligand: TLR2
Zymosan, peptidoglycans, lipoteichoic acids, lipoarabinomannan, porins, envelope glycoproteins
27
TLR-Ligand: TLR3
dsRNA
28
TLR-Ligand: TLR4
LPS, lipoprotein, HSP60 (chlaymida), fusion protein (RSV)
29
TLR-Ligand: TLR5
Flagellin
30
TLR-Ligand: TLR6
Diacyl lipopeptides (mycoplasma), lipoteichoic acid (G+ bacteria)
31
TLR-Ligand: TLR7&8
ssRNA and short dsRNA
32
TLR-Ligand: TLR9
Unmethylated CpG DNA
33
TLR-Ligand: TLR10
Unknown
34
TLR-Ligand: TLR11
Profilin and flagellin (apicomplexan parasites)
35
TLR-Ligand: TLR12
Profilin (apicomplexan parasites)
36
TLR-Ligand: TLR13
Bacterial 23S rRNA (G- bacteria)
37
Key cell types expressing TLRs
APCs (including macrophages, DCs, and B lymphocytes)
38
Cytosolic receptors that function in pattern recognition of viral and bacterial pathogens
1) NLRs (NOD-like receptors)
2) RLRs (RIG-I-like receptors)
39
NLRs consists of
N-terminal effector region
Centrally located NOD (or NACHT)
C-terminal LRR that sense PAMPs
40
Makes up the N-terminal effector region of NLRs
CARD or Pyrin domain or Acidic domain or BIRs
41
NLRs containing a pyrin domain
NLRPs
42
Most well-characterized among NLRs
1) NOD family
2) NLRPs
43
NODs that are involved in sensing bacterial molecules derived from synthesis and degradation of peptidoglycan
NOD1 and NOD2
44
NOD that recognizes diaminopimelic acid produced primarily by G- bacteria
NOD1
45
NOD that recognizes muramyl dipeptide (MDP), a component of both G+ and G- bacteria
NOD2
46
T/F DAMPs also activate PRRs
T
47
Receptors on macrophage surface
1) PRR
2) CD40
3) Fc and complement receptors
48
DAMPs released during necrotic or inflammatory based cell death
Alarmins
49
Calcium-binding proteins expressed in the cytoplasm of phagocytes and secreted by activated monocytes and neutrophils
Calgranulins (S100A8, S100A9, and S100A12)
50
3 major downstream signaling pathways responsible for mediating TLR-induced responses
1) NF-κB
2) MAPKs
3) IRFs
51
Downstream signaling pathways: Play central roles in induction of a proinflammatory response
1) NF-κB
2) MAPKs
52
Downstream signaling pathways: Essential for stimulation of IFN production
IRFs
53
MAPK-activated pathways
p38, JNK, ERK
54
TLR signaling pathway that induces the early-phase NF-κB and MAPK activation that controls the induction of proinflammatory cytokines
MyD88-dependent signaling pathway
55
TLR signaling pathway that activates IRF3, which is required for induction of IFN-β and IFN-inducible genes
MyD88-independent signaling pathway
56
TLR signaling pathway that mediates the late-phase NF-κB and MAPK activation
MyD88-independent signaling pathway
57
Th1- vs Th2-related cytokines: IFN-γ
Th1
58
Th1- vs Th2-related cytokines: Polarize macrophages to an M1 phenotype
Th1
59
Th1- vs Th2-related cytokines: IL-4
Th2
60
Th1- vs Th2-related cytokines: IL-13
Th2
61
Th1- vs Th2-related cytokines: Polarize macrophages to an M2 phenotype
Th2
62
M1 vs M2 macrophages: Dampen inflammation
M2
63
M1 vs M2 macrophages: Promote tissue remodeling and repair
M2
64
M1 vs M2 macrophages: Help in parasite clearance
M2
65
M1 vs M2 macrophages: Suppress tumor immunosurveillance
M2
66
T/F A single macrophage can change between M1 and M2 phenotype function in response to changes in the local environment
T
67
Interferons are a treatable target using
1) Monoclonal Ab that blocks either the cyokine or receptor
2) JAKi that blocks IFNAR (Type 1 IFN receptor) signaling
68
Protein complex responsible for production of biologically active IL-1 (i.e. secretion of mature IL-1β and IL-18)
Inflammasome
69
NLR that has been ascribed a role in recognition of uric acid crystals
NLRP3
70
Components of inflammasome
1) Adaptor ASC
2) Procaspase-1
3) An NLR
71
Mutations in the NLRP3 and NLRC4 genes in humans are associated with disease characterized by excessive production of IL-1β and IL-18, which are called
Autoinflammatory diseases
72
Activated vs inactive pyrin: Phosphorylated form
Inactive or blocked form
73
Distinct subtype of DCs that display unique capacity to secrete large amounts of type I IFN (α/β) in response to certain viruses and other stimuli
pDCs aka plasmacytoid interferon producing cells
74
Trigger TLR7&9 expressed by pDCs, leading to type I IFN production
Viral nucleic acids
Self-nucleoproteins internalized in the form of immune complexes
75
Diseases with increased Type I IFN signaling, hence pDCs have been implicated in their pathophysiology
SLE, JDM
76
First signals for gene expression and synthesis of inactive IL-1β and IL-18 precursors in the canonical activation of inflammasome
TLR ligands
77
Second signals for gene expression and synthesis of inactive IL-1β and IL-18 precursors in the canonical activation of inflammasome
Exogenous ATP OR mitochondrial ROS
78
Protein mutated in FMF (gain of function mutation) that is able to form with ASC and caspase 1 its own inflammasome
Pyrin (aka MEFV)
79
Activates the serine-threonine kinases PKN1 and PKN2 that phsophorylate and block pyrin
GTPase RhoA
80
Pyrin inflammasome activation inactivates ___ resulting in dephosphorylation of pyrin
GTPase RhoA
81
2 major subsets of NK cells are identified according to
Level of expression of CD56: CD56dim and CD56bright
82
CD56dim vs CD56bright: 90% of NK cells in peripheral blood
CD56dim
83
CD56dim and CD56bright: Immature
CD56bright
84
CD56dim and CD56bright: Plays a major role in cytokine production
CD56bright
85
CD56dim and CD56bright: Better able to leave the circulation
CD56bright
86
CD56dim and CD56bright: Constitutes majority of NK cells in lymphoid organs
CD56bright
87
Binds with inhibitory receptor on NK cell
MHC I
88
Leads to loss of MHC I expression of cell, thereby lack of ligand for inhibitory receptor of NK cell leading to killing of the affected cell
Viral infection
89
Receptors on NK cell
Activating receptor
Inhibitory receptor
Fc receptor (FcγRIIIa)
90
Potent inducer of NK cell IFN-γ secretion and cytolytic activity
IL-12 produced by macrophages
91
Cytokine secreted by NK cell that further activates macrophages to kill phagocytosed microbes
IFN-γ
92
Lymphoid derived cells with effector functions that parallel that of T cells but do not bear a T cell receptor and instead respond to stimuli in an innate-like fashion
Innate lymphoid cells (ILCs)
93
Innate lymphoid cells (ILCs): Produce cytokines typically associated with Th1 T-cell responses
Group 1 ILCs
94
Innate lymphoid cells (ILCs): Share many of the effector functions of CD4+ Th2 cells
Group 2 ILCs
95
Innate lymphoid cells (ILCs): Have cytotoxic functions like CD8+ T cells
Group 1 ILCs
96
Innate lymphoid cells (ILCs): Predominate in the intestinal mucosa and may contribute to IBD
Group 3 ILCs
97
Innate lymphoid cells (ILCs): NK cells are a major component of this group
Group 1 ILCs
98
Innate lymphoid cells (ILCs): Thought to be important in antihelminthic responses
Group 2 ILCs
99
Innate lymphoid cells (ILCs): Express the transcription factor RORγT
Group 3 ILCs
100
Innate lymphoid cells (ILCs): Make IL-17 and IL-22 much like Th17 cells
Group 3 ILCs
101
Innate lymphoid cells (ILCs): Found in synovial fluid of children with JIA
Group 3 ILCs
102
Pathway of complement activation: Activated by direct binding of C3b to microbial cells
Alternative pathway
103
Pathway of complement activation: Activated by binding of C1 to CH2 domains of IgG or CH3 domains of IgM that have bound antigen
Classical pathway
104
Pathway of complement activation: Activated by direct recognition of carbohydrate or acetylated PAMPs by MBL and ficolins
Lectin pathway
105
3 pathways of complement activation converge upon this central protein
C3
106
Type 1 vs type 2 complement receptor: CR1
Type 1
107
Type 1 vs type 2 complement receptor: CD35
Type 1
108
Type 1 vs type 2 complement receptor: CR2
Type 2
109
Type 1 vs type 2 complement receptor: CD21
Type 2
110
Type 1 vs type 2 complement receptor: Expressed by almost all blood cells
Type 1
111
Type 1 vs type 2 complement receptor: Present on B lymphocytes and follicular DCs of LN germinal centers
Type 2
112
Type 1 vs type 2 complement receptor: Mainly functions as co-receptor for B cell activation by antigen
Type 2
113
Type 1 vs type 2 complement receptor: Promotes phagocytosis of C3b coated microbes
Type 1
114
Type 1 vs type 2 complement receptor: Mainly functions to stimulate trapping of antigen-antibody complexes in germinal centers
Type 2
115
Complement receptor expressed on RBCs that bind to immune complexes with attached C3b thereby transporting these complexes to the liver and spleen where they are removed from the erythrocyte surface and cleared
CR1
116
Complement receptors that are members of the integrin family and are expressed by innate immune system cells
Type 3 and 4 complement receptors
117
Complement receptors that promotes activation of innate cells resulting in phagocytosis of microbes opsonized with C3b
CR3 and CR4
118
Complement receptor: Clearance of immune complexes
CR1 (CD35)
119
Complement receptor: Receptor for EBV
CR2 (CD21)
120
Complement receptor: Adhesion to endothelium via ICAM
CR3 (CD11b/CD18)
121
Deficiency of this complement component is associated with serious pyogenic infections
C3
122
Defects of this complement component is associated with increased risk of disseminated Neisseria infections
Terminal complement components C5-C9
123
Deficiency of this protein, which functions to regulate the proteolytic activity of C1, the initiator of the classical pathway, causes hereditary angioedema
C1 inhibitor
124
Characterized by excess alternative pathway activation leading to C3 consumption and glomerulonephritis
Deficiency of factor H
125
Adhesion molecules constitutively expressed on circulating leukocytes that ensures firm adherence of leukocytes to endothelial cells
Integrins
126
Weak adhesion of leukocytes to the endothelium
Rolling
127
Adhesion molecule-cell distribution-ligand-main function: P-selectin
Activated endothelium; sialyl lewis x; initiate leukocyte-endothelium interaction
128
Adhesion molecule-cell distribution-ligand-main function: E-selectin
Platelets; PSGL-1; -
129
Adhesion molecule-cell distribution-ligand-main function: L-selectin
Activated endothelium & leukocytes; GlyCAM-1, CD34, MADCAM-1; -
130
Adhesion molecule-cell distribution-ligand-main function: VLA4-5
Leukocytes; JAM-B; homing to inflamed tissue
131
Adhesion molecule-cell distribution-ligand-main function: LFA-1
Leukocytes; ICAM-1/3, JAM-A; Leukocyte adhesion to endothelium
132
Adhesion molecule-cell distribution-ligand-main function: VE-cadherin
Endothelium lateral junctions; VE-cadherin; cell to cell adhesion
133
Adhesion molecule-cell distribution-ligand-main function: VLA-4
Leukocytes; VCAM-1; leukocyte adhesion to endothelium
134
Cytokines are classified in these 5 main categories
1) Interleukins
2) Interferons
3) Pro- and anti-inflammatory cytokines
4) Chemokines
5) Growth factors
135
Interleukins
IL-2,4,5,7,12,13,15,18,23
136
Proinflammatory cytokines
IL-1α, IL-1β, TNF-α
IL-6,17,22
137
Antiinflamatory cytokines
IL-10, TGF-β
138
Interferons
Type I IFNs: IFNα, IFNβ
IFNγ
139
T/F Cytokines typically act locally in autocrine or paracrine fashion
T
140
Endocrine functions of TNF
1) Stimulate the hypothalamus to induce fever
2) Stimulate hepatocytes to produce acute phase reactants
3) Promote metabolic changes leading to cachexia
141
Proinflammatory cytokine which plays a major role in septic shock
TNF
142
Major source of TNF
Activated macrophages
143
Major source of IL-1
Activated macrophages
144
Interleukins, main biological effect: Synthesis of IFN-γ by T cells and NK cells
IL-12 and IL-18
145
Interleukins, main biological effect: Differentiation of Th17 cells
IL-23
146
Interleukins, main cell source: Il-12
Th2 cells, B cells, DC, macrophages
147
Interleukins, main cell source: IL-23
DC
148
Proinflammatory cytokines, main biological effect: Fever
IL-1, IL-6, TNF-α
149
Proinflammatory cytokines, main biological effect: Acute phase reactants
IL-1, IL-6, TNF-α
150
Proinflammatory cytokines, main biological effect: Cachexia
TNF-α
151
Proinflammatory cytokines, main biological effect: Activation of endothelial cells
IL-1, TNF-α, IL-17
152
Proinflammatory cytokines, main biological effect: B cell proliferation
IL-6
153
Antiinflammatory cytokines, main biological function: Suppression of macrophage function
IL-10
154
Antiinflammatory cytokines, main biological function: Inhibition of T and B cells
TGF-β
155
Interferons, main biological function: Antiviral response
Type I IFN
156
Interferons, main biological function: Activation of NK cells
IFN-α,β,γ
157
Interferons, main biological function: Induction of MHC-I on somatic cells and MHC-II on APCs
IFN-γ
158
Chemokine, main function: Angiogenesis
CXCL7
159
Chemokine, main function: HIV coreceptor
CCL4
160
Chemokine, main function: Allergy
CCL11
161
Chemokine, main function: Lymphocyte homing to lymphoid organs
CXCL13
162
Chemokine, main function: T cell migration to skin
CCL25 and 27
163
Chemokine, main function: Brain inflammation
CX3CL1
164
Chemokine, main function: Lymphocyte trafficking and development
XCL1
165
IL-1 receptor: Constitutively expressed on many cell types
Type I
166
IL-1 receptor: Mediates intracellular signal transmission through IRAK, leading to NF-κB and AP-1 transcription factors
Type I
167
IL-1 receptor: Expressed only after cell activation
Type II
168
IL-1 receptor: Binding with IL-1 does not result in intracellular signal transmission
Type II
169
IL-1 receptor: Down-modulate biological action of IL-1 by acting as decoy receptor
Type II
170
2 strategies for IL-1 down-modulation
1) Binding to Type II receptor
2) Binding of IL-Ra (IL-1 receptor antagonist) to IL-1 receptors but is biologically inactive
171
IL closely related to IL-1β and is particularly associated with NLRC4 inflammasome
IL-18
172
A soluble factor that binds to IL-18 and prevents its ability to ligate and activate IL-18 receptor
IL-18BP
173
Stimulates synthesis of APRs by the liver and production and release of neutrophils from bone marrow
IL-6
174
Cytokine that plays a pivotal role in sJIA
IL-6
175
Chemokines produced by leukocytes and resident tissues in response to proinflammatory stimuli
Inflammatory chemokines
176
Chemokines constitutively expressed by in the microenvironment of lymphoid tissues, skin, and mucosa involved in continuous leukocyte trafficking between circulation and lymphoid structures
Homing chemokines
177
Responsible for the production of prostaglandins both in physiological and pathological conditions
COX
178
COX that is constitutively expressed in most tissues
COX-1
179
COX that is normally undetectable in normal tissues but can be rapidly induced in particular cell types
COX-2
180
Cell types where COX-2 can be induced upon proinflammatory stimulation
Fibroblasts, monocytes, endothelial cells
181
Most abundant COX-2 product
PGE2 and mast cell-derived PGD2
182
Prostaglandin that plays a crucial role in the induction of fever after stimulation of specialized endothelial cells in hypothalamic tissue by endogenous pyrogens
PGE2
183
Endogenous pyrogens
TNF and IL-6
184
Derived from the combined actions of 5-LOX and FLAP with initial formation of 5-HPETE
Leukotrienes
185
Main function of matrix metalloproteinases
Remodeling of ECM during tissue resorption
