Innate Immune Defences & Inflammation 2: The Induced Response Flashcards
1
Q
Cells of the innate & adaptive immune system
- The discovery of innate lymphoid cells (ILCs) is blurring the traditional boundaries between innate and adaptive immune systems. Invariant natural killer T cells, some B cells at epithelial barriers (B1 cells) and gamma delta T cells have innate qualities whereas NK cells may adapt after their first encounter with a pathogen due to innate immune memory. T and B cells also have innate immune receptors such as TLRs.
A
- The discovery of innate lymphoid cells (ILCs) is blurring the traditional boundaries between innate and adaptive immune systems. Invariant natural killer T cells, some B cells at epithelial barriers (B1 cells) and gamma delta T cells have innate qualities whereas NK cells may adapt after their first encounter with a pathogen due to innate immune memory. T and B cells also have innate immune receptors such as TLRs.
2
Q
Innate immune cells
- What cells are involved? What do they do?
A
- Neutrophils - Phagocytosis, Antimicrobial peptides, Reactive oxygen and nitrogen species
- Macrophages - Phagocytosis, Antimicrobial peptides, Reactive oxygen and nitrogen species, Inflammatory mediators, antigen presentation, cytokines, complement proteins
- Dendritic cells - Antigen presentation, Costimulatory signals, Reactive oxygen species, Interferon, Cytokines
- Natural Killer cells - Lysis of viral-infected cells, Interferon, Macrophage activation, Granzyme, Perforin
3
Q
What are the functions of a neutrophil?
A
- Phagocytosis, Antimicrobial peptides, Reactive oxygen and nitrogen species
4
Q
What are the functions of a macrophage?
A
- Phagocytosis, Antimicrobial peptides, Reactive oxygen and nitrogen species, Inflammatory mediators, antigen presentation, cytokines, complement proteins
5
Q
What are the functions of dendritic cells?
A
- Antigen presentation, Costimulatory signals, Reactive oxygen species, Interferon, Cytokines (Plasmacytoid dendritic cells (DCs) are of lymphoid origin, Myeloid DCs are of myeloid origin - plasmacytoid DCs produce large amounts of type 1 IFN whereas for myeloid DCs the main role is antigen presentation)
6
Q
What are the functions of natural killer cells?
A
- Lysis of viral-infected cells, Interferon, Macrophage activation, Granzyme, Perforin (Perforin is pore forming permitting entry of granzyme into cells where it induces apoptosis)
7
Q
… is pore forming permitting entry of granzyme into cells where it induces apoptosis.
A
Perforin is pore forming permitting entry of granzyme into cells where it induces apoptosis.
8
Q
Plasmacytoid dendritic cells (DCs) are of … origin
A
Plasmacytoid dendritic cells (DCs) are of lymphoid origin
9
Q
Myeloid DCs are of … origin
A
Myeloid DCs are of myeloid origin
10
Q
… DCs produce large amounts of type 1 IFN whereas for … DCs the main role is antigen presentation
A
plasmacytoid DCs produce large amounts of type 1 IFN whereas for myeloid DCs the main role is antigen presentation
11
Q
Phagocyte recruitment
- … produced by macrophages dilate local blood vessels and increase endothelial adhesion molecule expression.
- … attract monocytes and neutrophils to the infection
- Cell adhesion molecules (ICAM-1 and VCAM-1) are upregulated on the endothelium which bind to integrins (family of adhesion molecules) on the leukocytes
A
- Cytokines produced by macrophages dilate local blood vessels and increase endothelial adhesion molecule expression.
- Chemokines attract monocytes and neutrophils to the infection
- Cell adhesion molecules (ICAM-1 and VCAM-1) are upregulated on the endothelium which bind to integrins (family of adhesion molecules) on the leukocytes
12
Q
Phagocyte recruitment
- Cytokines produced by macrophages … local blood vessels and … endothelial adhesion molecule expression.
- Chemokines attract monocytes and … to the infection
- Cell adhesion molecules (ICAM-1 and VCAM-1) are upregulated on the endothelium which bind to integrins (family of adhesion molecules) on the leukocytes
A
- Cytokines produced by macrophages dilate local blood vessels and increase endothelial adhesion molecule expression.
- Chemokines attract monocytes and neutrophils to the infection
- Cell adhesion molecules (ICAM-1 and VCAM-1) are upregulated on the endothelium which bind to integrins (family of adhesion molecules) on the leukocytes
13
Q
Phagocyte recruitment
- Cytokines produced by macrophages dilate local blood vessels and increase endothelial adhesion molecule expression.
- Chemokines attract monocytes and neutrophils to the infection
- Cell … molecules (ICAM-1 and VCAM-1) are upregulated on the endothelium which bind to integrins (family of … molecules) on the leukocytes
A
- Cytokines produced by macrophages dilate local blood vessels and increase endothelial adhesion molecule expression.
- Chemokines attract monocytes and neutrophils to the infection
- Cell adhesion molecules (ICAM-1 and VCAM-1) are upregulated on the endothelium which bind to integrins (family of adhesion molecules) on the leukocytes
14
Q
Phagocyte recruitment
- Cytokines produced by macrophages dilate local blood vessels and increase endothelial adhesion molecule expression.
- Chemokines attract monocytes and neutrophils to the infection
- Cell adhesion molecules (…-1 and …-1) are upregulated on the endothelium which bind to integrins (family of adhesion molecules) on the leukocytes
A
- Cytokines produced by macrophages dilate local blood vessels and increase endothelial adhesion molecule expression.
- Chemokines attract monocytes and neutrophils to the infection
- Cell adhesion molecules (ICAM-1 and VCAM-1) are upregulated on the endothelium which bind to integrins (family of adhesion molecules) on the leukocytes
15
Q
Phagocytosis is performed by …, … cells and …
A
Phagocytosis is performed by neutrophils, dendritic cells and macrophages
16
Q
Neutrophils, Dendritic Cells and Macrophages all perform…
A
phagocytosis
17
Q
Phagocytosis is the … and … of … particles
A
Phagocytosis is the capture and digestion of foreign particles
18
Q
Phagocytosis is the … and … of … particles
A
Phagocytosis is the capture and digestion of foreign particles
19
Q
What is phagocytosis?
A
Phagocytosis is the capture and digestion of foreign particles
20
Q
… are proteins of the innate and adaptive immune system that facilitate phagocytosis and cell lysis by “marking” antigen.
A
Opsonins are proteins of the innate and adaptive immune system that facilitate phagocytosis and cell lysis by “marking” antigen.
21
Q
Complement components (C3b) and Collectins (Mannose-binding lectin) and antibodies are all good examples of …
A
opsonins (opsonins are proteins of the innate and adaptive immune system that facilitate phagocytosis and cell lysis by “marking” antigen.)
22
Q
Opsonins engage with … receptors (complement receptors, fc receptors, Mannose receptor, Scavenger receptors)
A
Opsonins engage with phagocytic receptors (complement receptors, fc receptors, Mannose receptor, Scavenger receptors)
23
Q
… receptors recognize bacteria, viruses and apoptotic cells
A
Scavenger receptors recognize bacteria, viruses and apoptotic cells
24
Q
The complement receptor CR1 binds to … (complement component)
A
The complement receptor CR1 binds to C3b (complement component)
25
Q
C-type-lectin receptors (Dectin-1 & mannose receptor) help … bacteria. Mannose Receptor binds mannose and fructose residues of glycans (polysaccharides).
A
C-type-lectin receptors (Dectin-1 & mannose receptor) help phagocytose bacteria. Mannose Receptor binds mannose and fructose residues of glycans (polysaccharides).
26
Q
Receptor mediated phagocytosis
- … receptors bind to opsonins
- Microorganisms are internalised by receptor-mediated endocytosis
- Fusion of … with lysosome forms a phagolysosome in which microorganisms are degraded
A
- Phagocytic receptors bind to opsonins
- Microorganisms are internalised by receptor-mediated endocytosis
- Fusion of endosome with lysosome forms a phagolysosome in which microorganisms are degraded
27
Q
Receptor mediated phagocytosis
- Phagocytic receptors bind to opsonins
- Microorganisms are internalised by receptor-mediated endocytosis
- Fusion of endosome with … forms a … in which microorganisms are degraded
A
- Phagocytic receptors bind to opsonins
- Microorganisms are internalised by receptor-mediated endocytosis
- Fusion of endosome with lysosome forms a phagolysosome in which microorganisms are degraded
28
Q
Receptor mediated phagocytosis
- Phagocytic receptors bind to …
- Microorganisms are internalised by receptor-mediated endocytosis
- Fusion of endosome with lysosome forms a phagolysosome in which microorganisms are degraded
A
- Phagocytic receptors bind to opsonins
- Microorganisms are internalised by receptor-mediated endocytosis
- Fusion of endosome with lysosome forms a phagolysosome in which microorganisms are degraded
29
Q
Receptor mediated phagocytosis
- Phagocytic receptors bind to opsonins
- Microorganisms are internalised by receptor-mediated …
- Fusion of endosome with lysosome forms a phagolysosome in which microorganisms are degraded
A
- Phagocytic receptors bind to opsonins
- Microorganisms are internalised by receptor-mediated endocytosis
- Fusion of endosome with lysosome forms a phagolysosome in which microorganisms are degraded
30
Q
Lysosomes can fuse with … to form a …
A
Lysosomes can fuse with phagosomes to form a phagolysosome
31
Q
Antimicrobial mechanisms of phagocytes
- Within phagolysosome:
- … environment - … pH
- Oxygen and nitrogen derived products - break down pathogens
- Antimicrobial … are present
- Enzymes such as lysozyme - digests cell walls of some gram+ bacteria
- Lactoferrin - binds Fe2+ which is needed for bacterial growth (competitor)
A
- Within phagolysosome:
- Acidic environment - Low pH
- Oxygen and nitrogen derived products - break down pathogens
- Antimicrobial peptides are present
- Enzymes such as lysozyme - digests cell walls of some gram+ bacteria
- Lactoferrin - binds Fe2+ which is needed for bacterial growth (competitor)
32
Q
Antimicrobial mechanisms of phagocytes
- Within phagolysosome:
- Acidic environment - Low pH
- Oxygen and nitrogen derived products - break down pathogens
- Antimicrobial peptides are present
- Enzymes such as … - digests cell walls of some gram+ bacteria
- Lactoferrin - binds Fe2+ which is needed for bacterial growth (competitor)
A
- Within phagolysosome:
- Acidic environment - Low pH
- Oxygen and nitrogen derived products - break down pathogens
- Antimicrobial peptides are present
- Enzymes such as lysozyme - digests cell walls of some gram+ bacteria
- Lactoferrin - binds Fe2+ which is needed for bacterial growth (competitor)
33
Q
Antimicrobial mechanisms of phagocytes
- Within phagolysosome:
- Acidic environment - Low pH
- Oxygen and nitrogen derived products - break down pathogens
- Antimicrobial peptides are present
- Enzymes such as lysozyme - digests cell walls of some gram… bacteria
- … - binds Fe2+ which is needed for bacterial growth (competitor)
A
- Within phagolysosome:
- Acidic environment - Low pH
- Oxygen and nitrogen derived products - break down pathogens
- Antimicrobial peptides are present
- Enzymes such as lysozyme - digests cell walls of some gram+ bacteria
- Lactoferrin - binds Fe2+ which is needed for bacterial growth (competitor)
34
Q
Antimicrobial mechanisms of phagocytes
- Within phagolysosome:
- Acidic environment - Low pH
- … and … derived products - break down pathogens
- Antimicrobial peptides are present
- Enzymes such as lysozyme - digests cell walls of some gram+ bacteria
- Lactoferrin - binds Fe2+ which is needed for … …
A
- Within phagolysosome:
- Acidic environment - Low pH
- Oxygen and nitrogen derived products - break down pathogens
- Antimicrobial peptides are present
- Enzymes such as lysozyme - digests cell walls of some gram+ bacteria
- Lactoferrin - binds Fe2+ which is needed for bacterial growth (competitor)
35
Q
Neutrophil Extracellular Traps (NETs)
- When activated some neutrophils undergo a special form of cell death termed ‘…’
- During … nuclear chromatin is released from cells trapping microorganisms thus aiding phagocytosis
A
- When activated some neutrophils undergo a special form of cell death termed ‘NETosis’
- During NETosis nuclear chromatin is released from cells trapping microorganisms thus aiding phagocytosis
36
Q
Neutrophil Extracellular Traps (NETs)
- When activated some neutrophils undergo a special form of cell … termed ‘NETosis’
- During NETosis nuclear chromatin is released from cells trapping microorganisms thus aiding phagocytosis
A
- When activated some neutrophils undergo a special form of cell death termed ‘NETosis’
- During NETosis nuclear chromatin is released from cells trapping microorganisms thus aiding phagocytosis
37
Q
Neutrophil Extracellular Traps (NETs)
- When activated some neutrophils undergo a special form of cell death termed ‘NETosis’
- During NETosis nuclear … is released from cells trapping microorganisms thus aiding phagocytosis
A
- When activated some neutrophils undergo a special form of cell death termed ‘NETosis’
- During NETosis nuclear chromatin is released from cells trapping microorganisms thus aiding phagocytosis
38
Q
Neutrophil Extracellular Traps (NETs)
- When activated some neutrophils undergo a special form of cell death termed ‘NETosis’
- During NETosis nuclear chromatin is released from cells trapping microorganisms thus aiding …
A
- When activated some neutrophils undergo a special form of cell death termed ‘NETosis’
- During NETosis nuclear chromatin is released from cells trapping microorganisms thus aiding phagocytosis
39
Q
During NETosis nuclear … is released from cells trapping microorganisms thus aiding phagocytosis
A
During NETosis nuclear chromatin is released from cells trapping microorganisms thus aiding phagocytosis
40
Q
During NETosis nuclear chromatin is released from cells trapping microorganisms thus aiding …
A
During NETosis nuclear chromatin is released from cells trapping microorganisms thus aiding phagocytosis
41
Q
When activated some neutrophils undergo a special form of cell death termed ‘…’
A
When activated some neutrophils undergo a special form of cell death termed ‘NETosis’
42
Q
Pattern recognition receptors (PRRs)
- How many families of PRRs are there?
- What are they called?
A
- 5 families
- C type lectin receptors (CLRs), Toll-like receptors (TLRs), NOD-like receptors (NLRs), Rig-I like receptors (RLRs), Cytosolic DNA sensors (CDS)
43
Q
Pattern recognition receptors (PRRs)
- How many families of PRRs are there?
- What are they called?
A
- 5 families
- C type lectin receptors (CLRs), Toll-like receptors (TLRs), NOD-like receptors (NLRs), Rig-I like receptors (RLRs), Cytosolic DNA sensors (CDS)
44
Q
Below are all different families of what?
- C type lectin receptors (CLRs)
- Toll-like receptors (TLRs)
- NOD-like receptors (NLRs)
- Rig-I like receptors (RLRs)
- Cytosolic DNA sensors (CDS)
A
Pattern recognition receptors (PRRs)
45
Q
… … … (…s) are receptors able to recognise conserved structures
A
Pattern recognition receptors (PRRs) are receptors able to recognise conserved structures
46
Q
Pattern recognition receptors (PRRs) recognise patterns termed: …-associated … … (…s)
A
Pattern recognition receptors (PRRs) recognise patterns termed: pathogen-associated molecular patterns (PAMPs)
47
Q
What do Pattern recognition receptors (PRRs) recognise ?
A
patterns termed: pathogen-associated molecular patterns (PAMPs)
48
Q
Pattern-associated molecular patterns (PAMPs) & DAMPs
- PAMPs - Microbes evolve rapidly, so innate immunity must focus on highly … and … components of microbes (cell wall structures; nucleic acids)
- DAMPs – Damage associated molecular patterns; molecules released from necrotic cells
A
- PAMPs - Microbes evolve rapidly, so innate immunity must focus on highly conserved and essential components of microbes (cell wall structures; nucleic acids)
- DAMPs – Damage associated molecular patterns; molecules released from necrotic cells
49
Q
Pattern-associated molecular patterns (PAMPs) & DAMPs
- PAMPs - Microbes evolve rapidly, so innate immunity must focus on highly conserved and essential components of microbes (cell wall structures; nucleic acids)
- DAMPs – … associated molecular patterns; molecules released from … cells
A
- PAMPs - Microbes evolve rapidly, so innate immunity must focus on highly conserved and essential components of microbes (cell wall structures; nucleic acids)
- DAMPs – Damage associated molecular patterns; molecules released from necrotic cells
50
Q
DAMPs – … associated … patterns; molecules released from necrotic cells
A
DAMPs – Damage associated molecular patterns; molecules released from necrotic cells
51
Q
C type lectin receptors (CLRs)
- CLRs are expressed by most cell type that phagocytose glycoproteins and microbes for antigen presentation to T lymphocytes
- CLRs bind to … in a calcium-dependent manner
- Type I CLRs assist with antigen uptake by phagocytes
- Type II CLRs are involved in fungal recognition
- Soluble CLRs include MBL that binds … on pathogen surfaces
A
- CLRs are expressed by most cell type that phagocytose glycoproteins and microbes for antigen presentation to T lymphocytes
- CLRs bind to carbohydrates in a calcium-dependent manner
- Type I CLRs assist with antigen uptake by phagocytes
- Type II CLRs are involved in fungal recognition
- Soluble CLRs include MBL that binds carbohydrates on pathogen surfaces
52
Q
C type lectin receptors (CLRs)
- CLRs are expressed by most cell type that phagocytose glycoproteins and microbes for antigen presentation to T lymphocytes
- CLRs bind to carbohydrates in a …-dependent manner
- Type I CLRs assist with antigen uptake by phagocytes
- Type II CLRs are involved in … recognition
- Soluble CLRs include MBL that binds carbohydrates on pathogen surfaces
A
- CLRs are expressed by most cell type that phagocytose glycoproteins and microbes for antigen presentation to T lymphocytes
- CLRs bind to carbohydrates in a calcium-dependent manner
- Type I CLRs assist with antigen uptake by phagocytes
- Type II CLRs are involved in fungal recognition
- Soluble CLRs include MBL that binds carbohydrates on pathogen surfaces
53
Q
C type lectin receptors (CLRs)
- CLRs are expressed by most cell type that phagocytose glycoproteins and microbes for antigen presentation to T lymphocytes
- CLRs bind to carbohydrates in a calcium-dependent manner
- Type I CLRs assist with … uptake by phagocytes
- Type II CLRs are involved in fungal recognition
- Soluble CLRs include MBL that binds carbohydrates on pathogen surfaces
A
- CLRs are expressed by most cell type that phagocytose glycoproteins and microbes for antigen presentation to T lymphocytes
- CLRs bind to carbohydrates in a calcium-dependent manner
- Type I CLRs assist with antigen uptake by phagocytes
- Type II CLRs are involved in fungal recognition
- Soluble CLRs include MBL that binds carbohydrates on pathogen surfaces
54
Q
CLRs are expressed by most cell type that … glycoproteins and microbes for … presentation to T lymphocytes
A
CLRs are expressed by most cell type that phagocytose glycoproteins and microbes for antigen presentation to T lymphocytes
55
Q
CLRs bind to … in a calcium-dependent manner
A
CLRs bind to carbohydrates in a calcium-dependent manner
56
Q
Type I CLRs assist with antigen uptake by …
A
Type I CLRs assist with antigen uptake by phagocytes
57
Q
Type II CLRs are involved in … recognition
A
Type II CLRs are involved in fungal recognition
58
Q
Soluble CLRs include … that binds carbohydrates on pathogen surfaces
A
Soluble CLRs include MBL that binds carbohydrates on pathogen surfaces
59
Q
Drosophila Toll Receptors
- Mutagenesis work on Drosophila revealed two members of the Toll family, dToll and 18-wheeler (dont need to know)
- Important for …
- Important for immunity to the fungal and bacterial infections
- Mammalian equivalent are the Toll-like receptors (TLRs)
A
- Mutagenesis work on Drosophila revealed two members of the Toll family, dToll and 18-wheeler (dont need to know)
- Important for development
- Important for immunity to the fungal and bacterial infections
- Mammalian equivalent are the Toll-like receptors (TLRs)
60
Q
Drosophila Toll Receptors
- Mutagenesis work on Drosophila revealed two members of the Toll family, dToll and 18-wheeler (dont need to know)
- Important for development
- Important for immunity to the fungal and bacterial infections
- Mammalian equivalent are the …-… receptors
A
- Mutagenesis work on Drosophila revealed two members of the Toll family, dToll and 18-wheeler (dont need to know)
- Important for development
- Important for immunity to the fungal and bacterial infections
- Mammalian equivalent are the Toll-like receptors (TLRs)
61
Q
Drosophila Toll Receptors
- Mutagenesis work on Drosophila revealed two members of the Toll family, dToll and 18-wheeler (dont need to know)
- Important for development
- Important for immunity to the … and … infections
- Mammalian equivalent are the Toll-like receptors (TLRs)
A
- Mutagenesis work on Drosophila revealed two members of the Toll family, dToll and 18-wheeler (dont need to know)
- Important for development
- Important for immunity to the fungal and bacterial infections
- Mammalian equivalent are the Toll-like receptors (TLRs)
62
Q
Toll-like receptor structure
- Extracellular:
- … domain – site of pathogen binding
- Cytosolic side:
- TIR-domain - conserved stretch of ~200 amino acids
A
- Extracellular:
- LRR domain – site of pathogen binding
- Cytosolic side:
- TIR-domain - conserved stretch of ~200 amino acids
63
Q
Toll-like receptor structure
- Extracellular:
- LRR domain – site of … binding
- Cytosolic side:
- TIR-domain - conserved stretch of ~200 amino acids
A
- Extracellular:
- LRR domain – site of pathogen binding
- Cytosolic side:
- TIR-domain - conserved stretch of ~200 amino acids
64
Q
Toll-like receptor structure
- Extracellular:
- LRR domain – site of pathogen binding
- Cytosolic side:
- …-domain - conserved stretch of ~200 amino acids
A
- Extracellular:
- LRR domain – site of pathogen binding
- Cytosolic side:
- TIR-domain - conserved stretch of ~200 amino acids
65
Q
Toll-like receptor structure
- Extracellular:
- LRR domain – site of pathogen binding
- … side:
- TIR-domain - conserved stretch of ~200 amino acids
A
- Extracellular:
- LRR domain – site of pathogen binding
-
Cytosolic side:
- TIR-domain - conserved stretch of ~200 amino acids
66
Q
TLRs form functional …/…dimers
A
TLRs form functional hetero/homodimers
67
Q
Cellular location of TLRS
- TLR-2 and TLR-6 recognise … lipopeptides (heterodimer)
- TLR-2 and TLR-1 recognise … lipopeptides (heterodimer)
- TLR-5 recognise flagellin
- TLR-4 recognise LPS on coat of gram- bacteria - works with MD-2
- The rest within endosome - recognise nucleic acid structures (TLRs 3, 7, 8, and 9 are situated in the membranes of endosomes and lysosomes)
- TLR10 is predominantly endosomal recognising dsRNA
A
- TLR-2 and TLR-6 recognise diacyl lipopeptides (heterodimer)
- TLR-2 and TLR-1 recognise triacyl lipopeptides (heterodimer)
- TLR-5 recognise flagellin
- TLR-4 recognise LPS on coat of gram- bacteria - works with MD-2
- The rest within endosome - recognise nucleic acid structures (TLRs 3, 7, 8, and 9 are situated in the membranes of endosomes and lysosomes)
- TLR10 is predominantly endosomal recognising dsRNA
68
Q
Cellular location of TLRS
- TLR-2 and TLR-6 recognise diacyl lipopeptides (heterodimer)
- TLR-2 and TLR-1 recognise triacyl lipopeptides (heterodimer)
- TLR-5 recognise …
- TLR-4 recognise LPS on coat of gram- bacteria - works with MD-2
- The rest within endosome - recognise nucleic acid structures (TLRs 3, 7, 8, and 9 are situated in the membranes of endosomes and lysosomes)
- TLR10 is predominantly endosomal recognising dsRNA
A
- TLR-2 and TLR-6 recognise diacyl lipopeptides (heterodimer)
- TLR-2 and TLR-1 recognise triacyl lipopeptides (heterodimer)
- TLR-5 recognise flagellin
- TLR-4 recognise LPS on coat of gram- bacteria - works with MD-2
- The rest within endosome - recognise nucleic acid structures (TLRs 3, 7, 8, and 9 are situated in the membranes of endosomes and lysosomes)
- TLR10 is predominantly endosomal recognising dsRNA
69
Q
Cellular location of TLRS
- TLR-2 and TLR-6 recognise diacyl lipopeptides (heterodimer)
- TLR-2 and TLR-1 recognise triacyl lipopeptides (heterodimer)
- TLR-5 recongise flagellin
- TLR-4 recognise … on coat of gram- bacteria - works with MD-2
- The rest within endosome - recognise nucleic acid structures (TLRs 3, 7, 8, and 9 are situated in the membranes of endosomes and lysosomes)
- TLR10 is predominantly endosomal recognising dsRNA
A
- TLR-2 and TLR-6 recognise diacyl lipopeptides (heterodimer)
- TLR-2 and TLR-1 recognise triacyl lipopeptides (heterodimer)
- TLR-5 recongise flagellin
- TLR-4 recognise LPS on coat of gram- bacteria - works with MD-2
- The rest within endosome - recognise nucleic acid structures (TLRs 3, 7, 8, and 9 are situated in the membranes of endosomes and lysosomes)
- TLR10 is predominantly endosomal recognising dsRNA
70
Q
Cellular location of TLRS
- TLR-2 and TLR-6 recognise diacyl lipopeptides (heterodimer)
- TLR-2 and TLR-1 recognise triacyl lipopeptides (heterodimer)
- TLR-5 recongise flagellin
- TLR-4 recognise LPS on coat of gram- bacteria - works with MD-2
- The rest within … - recognise nucleic acid structures (TLRs 3, 7, 8, and 9 are situated in the membranes of … and lysosomes)
- TLR10 is predominantly endosomal recognising dsRNA
A
- TLR-2 and TLR-6 recognise diacyl lipopeptides (heterodimer)
- TLR-2 and TLR-1 recognise triacyl lipopeptides (heterodimer)
- TLR-5 recongise flagellin
- TLR-4 recognise LPS on coat of gram- bacteria - works with MD-2
- The rest within endosome - recognise nucleic acid structures (TLRs 3, 7, 8, and 9 are situated in the membranes of endosomes and lysosomes)
- TLR10 is predominantly endosomal recognising dsRNA
71
Q
The TLRs include TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, TLR9, TLR10, TLR11, TLR12, and TLR13, though the last … are not found in humans.
A
The TLRs include TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, TLR9, TLR10, TLR11, TLR12, and TLR13, though the last three are not found in humans.
72
Q
TLR-… and TLR-… recognise diacyl lipopeptides (heterodimer)
A
TLR-2 and TLR-6 recognise diacyl lipopeptides (heterodimer)
73
Q
TLR-… and TLR-… recognise triacyl lipopeptides (heterodimer)
A
TLR-2 and TLR-1 recognise triacyl lipopeptides (heterodimer)
77
Q
TLR… is predominantly endosomal recognising dsRNA
A
TLR10 is predominantly endosomal recognising dsRNA
78
Q
TLR-3 recognises …-stranded RNA
A
TLR-3 recognises double-stranded RNA
79
Q
TLR-… recognises double-stranded RNA
A
TLR-3 recognises double-stranded RNA
80
Q
TLR-… recognises single-stranded RNA
A
TLR-7 recognises single-stranded RNA
81
Q
TLR-7 recognises …-stranded RNA
A
TLR-… recognises single-stranded RNA
82
Q
TLR-8 recognises …-stranded RNA
A
TLR-8 recognises single-stranded RNA
83
Q
TLR-… recongises CpG DNA
A
TLR-9 recongises CpG DNA
84
Q
Cell Surface TLRs (1,2,4,5,6) mainly recognise … products, but on our own host molecules recognise mainly … or … molecules
A
Cell Surface TLRs (1,2,4,5,6) mainly recognise bacterial products, but on our own host molecules recognise mainly lipid or protein molecules
85
Q
Cell Surface TLRs (which 5?) mainly recognise bacterial products, but on our own host molecules recognise mainly lipid or protein molecules
A
Cell Surface TLRs (1,2,4,5,6) mainly recognise bacterial products, but on our own host molecules recognise mainly lipid or protein molecules
86
Q
… TSRs (3,7,8,9,10) mainly recognise viral products, but on our host molecules recognise our own DNA or RNA (dsRNA, ssRNA, DNA)
A
Endosomal TSRs (3,7,8,9,10) mainly recognise viral products, but on our host molecules recognise our own DNA or RNA (dsRNA, ssRNA, DNA)
87
Q
Endosomal TSRs (which 5?) mainly recognise viral products, but on our host molecules recognise our own DNA or RNA (dsRNA, ssRNA, DNA)
A
Endosomal TSRs (3,7,8,9,10) mainly recognise viral products, but on our host molecules recognise our own DNA or RNA (dsRNA, ssRNA, DNA)
88
Q
Endosomal TSRs (3,7,8,9,10) mainly recognise viral products, but on our host molecules recognise our own … and …
A
Endosomal TSRs (3,7,8,9,10) mainly recognise viral products, but on our host molecules recognise our own DNA or RNA (dsRNA, ssRNA, DNA)
89
Q
Endosomal TSRs (3,7,8,9,10) mainly recognise … products, but on our host molecules recognise our own DNA or RNA (dsRNA, ssRNA, DNA)
A
Endosomal TSRs (3,7,8,9,10) mainly recognise viral products, but on our host molecules recognise our own DNA or RNA (dsRNA, ssRNA, DNA)
90
Q
TLRs recognise … and … ligands
A
TLRs recognise exogenous and endogenous ligands
91
Q
TLR signalling cascade
- TLR signalling induces genes that function in host defense:
- Pro-inflammatory & anti-inflammatory …
- MHC & co-stimulatory molecules
- antimicrobial peptides & complement components
A
- TLR signalling induces genes that function in host defense:
- Pro-inflammatory & anti-inflammatory cytokines
- MHC & co-stimulatory molecules
- antimicrobial peptides & complement components
92
Q
TLR signalling cascade
- TLR signalling induces genes that function in host defense:
- Pro-inflammatory & anti-inflammatory cytokines
- … & co-stimulatory molecules
- antimicrobial peptides & complement components
A
- TLR signalling induces genes that function in host defense:
- Pro-inflammatory & anti-inflammatory cytokines
- MHC & co-stimulatory molecules
- antimicrobial peptides & complement components
93
Q
TLR signalling cascade
- TLR signalling induces genes that function in host defense:
- Pro-inflammatory & anti-inflammatory cytokines
- MHC & co-stimulatory molecules
- antimicrobial peptides & complement components
A
- TLR signalling induces genes that function in host defense:
- Pro-inflammatory & anti-inflammatory cytokines
- MHC & co-stimulatory molecules
- antimicrobial peptides & complement components
94
Q
TLR signalling cascade
- TLR signalling induces genes that function in host defense:
- Pro-inflammatory & anti-inflammatory cytokines
- MHC & co-stimulatory molecules
- … peptides & … components
A
- TLR signalling induces genes that function in host defense:
- Pro-inflammatory & anti-inflammatory cytokines
- MHC & co-stimulatory molecules
- antimicrobial peptides & complement components
95
Q
TLR adaptor proteins
- Not all Toll-like receptors use all of the adaptor molecules
- TLR-… uses all of them
- TLR 3 only uses TRIF
- All apart from TLR3 use Myd88
A
- Not all Toll-like receptors use all of the adaptor molecules
- TLR-4 uses all of them
- TLR 3 only uses TRIF
- All apart from TLR3 use Myd88
96
Q
At the top of the TLR signalling cascade 4 different adaptive proteins are used. These are …
A
At the top of the TLR signalling cascade 4 different adaptive proteins are used. These are MyD88, MAL, TRIF and TRAM
97
Q
At the top of the TLR signalling cascade 4 different adaptive proteins are used. These are …
A
At the top of the TLR signalling cascade 4 different adaptive proteins are used. These are MyD88, MAL, TRIF and TRAM
98
Q
TLR adaptor proteins
- Not all Toll-like receptors use all of the adaptor molecules
- TLR-4 uses all of them
- TLR 3 only uses …
- All apart from TLR3 use Myd88
A
- Not all Toll-like receptors use all of the adaptor molecules
- TLR-4 uses all of them
- TLR 3 only uses TRIF
- All apart from TLR3 use Myd88
99
Q
TLR adaptor proteins
- Not all Toll-like receptors use all of the adaptor molecules
- TLR-4 uses all of them
- TLR 3 only uses TRIF
- All apart from TLR3 use …
A
- Not all Toll-like receptors use all of the adaptor molecules
- TLR-4 uses all of them
- TLR 3 only uses TRIF
- All apart from TLR3 use Myd88
100
Q
TLR adaptor proteins
- Not all Toll-like receptors use all of the … molecules
- TLR-4 uses all of them
- TLR 3 only uses TRIF
- All apart from TLR3 use Myd88
A
- Not all Toll-like receptors use all of the adaptor molecules
- TLR-4 uses all of them
- TLR 3 only uses TRIF
- All apart from TLR3 use Myd88
108
Q
A life without MyD88?
- Nine MyD88 deficient children suffered from life-threatening, often recurrent … bacterial infections, but were otherwise healthy, with normal resistance to other microbes.
- Their clinical status improved with …, possibly due to a compensatory effect of adaptive immunity or other innate immune mechanisms.
A
- Nine MyD88 deficient children suffered from life-threatening, often recurrent pyogenic bacterial infections, but were otherwise healthy, with normal resistance to other microbes.
- Their clinical status improved with age, possibly due to a compensatory effect of adaptive immunity or other innate immune mechanisms.
112
Q
TLRs in disease
A
113
Q
TLRs in disease
A
124
Q
What are the two major groups of NLRs?
A
NLRCs and NLRPs
125
Q
NLRCs
- Two examples: NLRC1 (…) and NLRC2 (…)
- They have a leucine rich domain which can bind to peptidoglycan which is present on the cell membrane of most bacteria
A
- Two examples: NLRC1 (NOD1) and NLRC2 (NOD2)
- They have a leucine rich domain which can bind to peptidoglycan which is present on the cell membrane of most bacteria
126
Q
NLRCs
- Two examples: NLRC1 (NOD1) and NLRC2 (NOD2)
- They have a … rich domain which can bind to … which is present on the cell membrane of most bacteria
A
- Two examples: NLRC1 (NOD1) and NLRC2 (NOD2)
- They have a leucine rich domain which can bind to peptidoglycan which is present on the cell membrane of most bacteria
127
Q
NOD1 and NOD2
- NOD1 and NOD2 detect similar yet distinct peptides of …
- NOD1 binds γ-glutamyl diaminopimelic acid (iE-DAP) (Mainly Gm-ve Bacteria)
- NOD2 binds muramyl dipeptide (both Gram+ve and Gram-ve bacteria)
A
- NOD1 and NOD2 detect similar yet distinct peptides of peptidoglycan
- NOD1 binds γ-glutamyl diaminopimelic acid (iE-DAP) (Mainly Gm-ve Bacteria)
- NOD2 binds muramyl dipeptide (both Gram+ve and Gram-ve bacteria)
128
Q
NOD1 and NOD2
- NOD1 and NOD2 detect similar yet distinct peptides of peptidoglycan
- NOD1 binds γ-glutamyl diaminopimelic acid (…-DAP) (Mainly Gm… Bacteria)
- NOD2 binds muramyl dipeptide (both Gram+ve and Gram-ve bacteria)
A
- NOD1 and NOD2 detect similar yet distinct peptides of peptidoglycan
- NOD1 binds γ-glutamyl diaminopimelic acid (iE-DAP) (Mainly Gm-ve Bacteria)
- NOD2 binds muramyl dipeptide (both Gram+ve and Gram-ve bacteria)
129
Q
NOD1 and NOD2
- NOD1 and NOD2 detect similar yet distinct peptides of peptidoglycan
- NOD1 binds γ-glutamyl diaminopimelic acid (iE-DAP) (Mainly Gm-ve Bacteria)
- NOD2 binds … dipeptide (both Gram+ve and Gram-ve bacteria)
A
- NOD1 and NOD2 detect similar yet distinct peptides of peptidoglycan
- NOD1 binds γ-glutamyl diaminopimelic acid (iE-DAP) (Mainly Gm-ve Bacteria)
- NOD2 binds muramyl dipeptide (both Gram+ve and Gram-ve bacteria)
136
Q
NLRPs
- The best characterised is NLRP… (NALP…)
- NLRP3 is activated by cellular stress; K+ efflux, ATP, reactive oxygen species and lysosomal damage
- Inflammasome activation is essential for IL-1 and IL-18 secretion
A
- The best characterised is NLRP3 (NALP3)
- NLRP3 is activated by cellular stress; K+ efflux, ATP, reactive oxygen species and lysosomal damage
- Inflammasome activation is essential for IL-1 and IL-18 secretion
137
Q
NLRPs
- The best characterised is NLRP… (NALP…)
- NLRP3 is activated by … stress; K+ efflux, ATP, reactive oxygen species and lysosomal damage
- Inflammasome activation is essential for IL-1 and IL-18 secretion
A
- The best characterised is NLRP3 (NALP3)
- NLRP3 is activated by cellular stress; K+ efflux, ATP, reactive oxygen species and lysosomal damage
- Inflammasome activation is essential for IL-1 and IL-18 secretion
138
Q
NLRPs
- The best characterised is NLRP… (NALP…)
- NLRP3 is activated by … stress; K+ efflux, ATP, reactive oxygen species and lysosomal damage
- … activation is essential for IL-1 and IL-18 secretion
A
- The best characterised is NLRP3 (NALP3)
- NLRP3 is activated by cellular stress; K+ efflux, ATP, reactive oxygen species and lysosomal damage
- Inflammasome activation is essential for IL-1 and IL-18 secretion
139
Q
Activation of the inflammasomes results in the processing and subsequent secretion of the pro-inflammatory cytokines IL-… and IL-…
A
Activation of the inflammasomes results in the processing and subsequent secretion of the pro-inflammatory cytokines IL-1 and IL-18.
140
Q
NLRP3 is activated by cellular stress; …+ efflux, A…, … oxygen species and lysosomal damage
A
NLRP3 is activated by cellular stress; K+ efflux, ATP, reactive oxygen species and lysosomal damage
141
Q
The Inflammasome senses danger
- Activated by cellular infection or cell …
- Stress caused by crystals getting stuck or bursting the phagosome during endocytosis (recognised - Uric acid crystals (gout))
A
- Activated by cellular infection or cell stress
- Stress caused by crystals getting stuck or bursting the phagosome during endocytosis (recognised - Uric acid crystals (gout))
142
Q
The Inflammasome senses danger
- Activated by cellular infection or cell stress
- Stress caused by … getting stuck or bursting the phagosome during endocytosis (recognised - Uric acid crystals (…))
A
- Activated by cellular infection or cell stress
- Stress caused by crystals getting stuck or bursting the phagosome during endocytosis (recognised - Uric acid crystals (gout))
143
Q
NALP3 Inflammasome
- Sensor of damage and cellular …
- … can form and are taken up by cells - this then drives activation and formation of the NALP3 inflammasome
- Conditions/Diseases/Infections such as: Gout, Asbestos, Silica, Amyloid beta (Alzheimer’s), Islet amyloid polypetide (T2 diabetes), Hemozoin (Malaria)
A
- Sensor of damage and cellular stress
-
Crystals can form and are taken up by cells - this then drives activation and formation of the NALP3 inflammasome
- Conditions/Diseases/Infections such as: Gout, Asbestos, Silica, Amyloid beta (Alzheimer’s), Islet amyloid polypetide (T2 diabetes), Hemozoin (Malaria)
144
Q
NALP3 Inflammasome
- Sensor of damage and cellular stress
- Crystals can form and are taken up by cells - this then drives activation and formation of the NALP3 inflammasome
- Conditions/Diseases/Infections such as: G…, As…, Silica, Amyloid beta (Alzheimer’s), Islet amyloid polypetide (T2 diabetes), Hemozoin (Malaria)
A
- Sensor of damage and cellular stress
- Crystals can form and are taken up by cells - this then drives activation and formation of the NALP3 inflammasome
- Conditions/Diseases/Infections such as: Gout, Asbestos, Silica, Amyloid beta (Alzheimer’s), Islet amyloid polypetide (T2 diabetes), Hemozoin (Malaria)
145
Q
NALP3 Inflammasome
- Sensor of damage and cellular stress
- Crystals can form and are taken up by cells - this then drives activation and formation of the NALP3 inflammasome
- Conditions/Diseases/Infections such as: Gout, Asbestos, Silica, Amyloid beta (…), Islet amyloid polypetide (… diabetes), Hemozoin (Malaria)
A
- Sensor of damage and cellular stress
- Crystals can form and are taken up by cells - this then drives activation and formation of the NALP3 inflammasome
- Conditions/Diseases/Infections such as: Gout, Asbestos, Silica, Amyloid beta (Alzheimer’s), Islet amyloid polypetide (T2 diabetes), Hemozoin (Malaria)
146
Q
NALP3 Inflammasome
- Sensor of damage and cellular stress
- Crystals can form and are taken up by cells - this then drives activation and formation of the NALP3 inflammasome
- Conditions/Diseases/Infections such as: Gout, Asbestos, Silica, Amyloid beta (Alzheimer’s), Islet amyloid polypetide (T2 diabetes), Hemozoin (M…)
A
- Sensor of damage and cellular stress
- Crystals can form and are taken up by cells - this then drives activation and formation of the NALP3 inflammasome
- Conditions/Diseases/Infections such as: Gout, Asbestos, Silica, Amyloid beta (Alzheimer’s), Islet amyloid polypetide (T2 diabetes), Hemozoin (Malaria)
147
Q
Frustrated phagocytosis
- … hip - fragments break off after grinding over years
- … by a macrophage - gets stuck in the process and puts cell under stress, leading to inflammasome activation and production of IL-1 and IL-18
- These people get inflamed hip, revision and tissue removed
A
- Artificial hip - fragments break off after grinding over years
- Phagocytosed by a macrophage - gets stuck in the process and puts cell under stress, leading to inflammasome activation and production of IL-1 and IL-18
- These people get inflamed hip, revision and tissue removed
148
Q
Frustrated phagocytosis
- Artificial hip - fragments break off after grinding over years
- Phagocytosed by a macrophage - gets stuck in the process and puts cell under stress, leading to inflammasome activation and production of IL-.. and IL-..
- These people get inflamed hip, revision and tissue removed
A
- Artificial hip - fragments break off after grinding over years
- Phagocytosed by a macrophage - gets stuck in the process and puts cell under stress, leading to inflammasome activation and production of IL-1 and IL-18
- These people get inflamed hip, revision and tissue removed
149
Q
Inflammasome cleavage of pro-IL-1 and pro-IL-18
- Activation of either IL-1 receptor family or toll-receptors - driving transcription and translation of IL-1B - made as pro-IL-1B - cleaved by …-1 released from inflammasome complex - makes mature active form of IL-1B
- Same process for IL-18 (requires cleavage by NALP3 inflammasome)
A
- Activation of either IL-1 receptor family or toll-receptors - driving transcription and translation of IL-1B - made as pro-IL-1B - cleaved by caspase-1 released from inflammasome complex - makes mature active form of IL-1B
- Same process for IL-18 (requires cleavage by NALP3 inflammasome)
150
Q
Inflammasome cleavage of pro-IL-1 and pro-IL-18
- Activation of either IL-1 receptor family or toll-receptors - driving transcription and translation of IL-1B - made as pro-IL-1B - cleaved by caspase-1 released from inflammasome complex - makes mature … form of IL-1B
- Same process for IL-18 (requires cleavage by NALP3 inflammasome)
A
- Activation of either IL-1 receptor family or toll-receptors - driving transcription and translation of IL-1B - made as pro-IL-1B - cleaved by caspase-1 released from inflammasome complex - makes mature active form of IL-1B
- Same process for IL-18 (requires cleavage by NALP3 inflammasome)
151
Q
Inflammasome cleavage of pro-IL-1 and pro-IL-18
- Activation of either IL-1 receptor family or toll-receptors - driving transcription and translation of IL-1B - made as pro-IL-1B - cleaved by caspase-1 released from inflammasome complex - makes mature active form of IL-1B
- Same process for IL-… (requires cleavage by NALP3 inflammasome)
A
- Activation of either IL-1 receptor family or toll-receptors - driving transcription and translation of IL-1B - made as pro-IL-1B - cleaved by caspase-1 released from inflammasome complex - makes mature active form of IL-1B
- Same process for IL-18 (requires cleavage by NALP3 inflammasome)
152
Q
Inflammasome cleavage of pro-IL-1 and pro-IL-18
- Activation of either IL-1 receptor family or toll-receptors - driving transcription and translation of IL-1B - made as pro-IL-1B - cleaved by …-1 released from inflammasome complex - makes mature active form of IL-1B
- Same process for IL-18 (requires cleavage by NALP3 inflammasome)
A
- Activation of either IL-1 receptor family or toll-receptors - driving transcription and translation of IL-1B - made as pro-IL-1B - cleaved by caspase-1 released from inflammasome complex - makes mature active form of IL-1B
- Same process for IL-18 (requires cleavage by NALP3 inflammasome)
153
Q
Gain of function mutations in NLRP3
- Cryopyrin-Associated Periodic Syndromes (…) - Caused by rare mutations in exon 3 of NLRP3 gene causing over production of IL-1
- 2 - Muckle wells syndrome (Prevalence unknown) and Familial cold autoinflammatory syndrome (1: 1000000)
A
- Cryopyrin-Associated Periodic Syndromes (CAPS) - Caused by rare mutations in exon 3 of NLRP3 gene causing over production of IL-1
- 2 - Muckle wells syndrome (Prevalence unknown) and Familial cold autoinflammatory syndrome (1: 1000000)
154
Q
Gain of function mutations in NLRP3
- Cryopyrin-Associated Periodic Syndromes (CAPS) - Caused by rare mutations in exon 3 of NLRP3 gene causing over production of IL-…
- 2 - Muckle wells syndrome (Prevalence unknown) and Familial cold autoinflammatory syndrome (1: 1000000)
A
- Cryopyrin-Associated Periodic Syndromes (CAPS) - Caused by rare mutations in exon 3 of NLRP3 gene causing over production of IL-1
- 2 - Muckle wells syndrome (Prevalence unknown) and Familial cold autoinflammatory syndrome (1: 1000000)
155
Q
Gain of function mutations in NLRP3
- Cryopyrin-Associated Periodic Syndromes (CAPS) - Caused by rare mutations in exon 3 of NLRP3 gene causing over production of IL-1
- 2 - … … syndrome (Prevalence unknown) and Familial cold autoinflammatory syndrome (1: 1000000)
A
- Cryopyrin-Associated Periodic Syndromes (CAPS) - Caused by rare mutations in exon 3 of NLRP3 gene causing over production of IL-1
- 2 - Muckle wells syndrome (Prevalence unknown) and Familial cold autoinflammatory syndrome (1: 1000000)
156
Q
Gain of function mutations in NLRP3
- Cryopyrin-Associated Periodic Syndromes (CAPS) - Caused by rare mutations in exon 3 of NLRP3 gene causing over production of IL-1
- 2 - Muckle wells syndrome (Prevalence unknown) and … … autoinflammatory syndrome (1: 1000000)
A
- Cryopyrin-Associated Periodic Syndromes (CAPS) - Caused by rare mutations in exon 3 of NLRP3 gene causing over production of IL-1
- 2 - Muckle wells syndrome (Prevalence unknown) and Familial cold autoinflammatory syndrome (1: 1000000)
164
Q
RIG-I-like receptors (RLRs)
- RIG-I and MDA5 are sensors of cytoplasmic …, a replication intermediate for viruses. They signal to induce pro-inflammatory … and IFN.
A
- RIG-I and MDA5 are sensors of cytoplasmic RNA, a replication intermediate for viruses. They signal to induce pro-inflammatory cytokines and IFN.
- RIG-I - Binds to single stranded RNA containing 5’-triphosphate (our 5’ RNA is capped so not recognised)
- MDA5 - Preferentially recognizes long double stranded RNA, Critical for picornavirus detection, Mutations are rare but have been associated with IFN related diseases, e.g. systemic lupus erythematosus and Aicardi–Goutières syndrome.
165
Q
RIG-I-like receptors (RLRs)
- RIG-I and MDA5 are sensors of cytoplasmic RNA, a replication intermediate for viruses. They signal to induce pro-inflammatory cytokines and IFN.
- RIG-I - Binds to … stranded RNA containing 5’-triphosphate (our 5’ RNA is capped so not recognised)
- MDA5 - Preferentially recognizes long … stranded RNA, Critical for picornavirus detection, Mutations are rare but have been associated with IFN related diseases, e.g. systemic lupus erythematosus and Aicardi–Goutières syndrome.
A
- RIG-I and MDA5 are sensors of cytoplasmic RNA, a replication intermediate for viruses. They signal to induce pro-inflammatory cytokines and IFN.
- RIG-I - Binds to single stranded RNA containing 5’-triphosphate (our 5’ RNA is capped so not recognised)
- MDA5 - Preferentially recognizes long double stranded RNA, Critical for picornavirus detection, Mutations are rare but have been associated with IFN related diseases, e.g. systemic lupus erythematosus and Aicardi–Goutières syndrome.
169
Q
Cytosolic DNA sensors
- Stimulator of interferon genes (STING)-associated vasculopathy with onset in infancy (SAVI) is an autoinflammatory disease caused by …-of-function mutations in the gene that codes for STING. Patients produce too much type 1 IFN causing abnormal inflammation throughout the body, especially in the skin, blood vessels, and lungs.
A
- Stimulator of interferon genes (STING)-associated vasculopathy with onset in infancy (SAVI) is an autoinflammatory disease caused by gain-of-function mutations in the gene that codes for STING. Patients produce too much type 1 IFN causing abnormal inflammation throughout the body, especially in the skin, blood vessels, and lungs.
170
Q
Cytosolic DNA sensors
- Stimulator of interferon genes (STING)-associated vasculopathy with onset in infancy (SAVI) is an autoinflammatory disease caused by gain-of-function mutations in the gene that codes for STING. Patients produce too much type 1 … causing abnormal inflammation throughout the body, especially in the skin, blood vessels, and lungs.
A
- Stimulator of interferon genes (STING)-associated vasculopathy with onset in infancy (SAVI) is an autoinflammatory disease caused by gain-of-function mutations in the gene that codes for STING. Patients produce too much type 1 IFN causing abnormal inflammation throughout the body, especially in the skin, blood vessels, and lungs.
171
Q
Cytosolic DNA sensors
- Stimulator of interferon genes (STING)-associated vasculopathy with onset in infancy (SAVI) is an autoinflammatory disease caused by gain-of-function mutations in the gene that codes for STING. Patients produce too much type … IFN causing abnormal inflammation throughout the body, especially in the skin, blood vessels, and lungs.
A
- Stimulator of interferon genes (STING)-associated vasculopathy with onset in infancy (SAVI) is an autoinflammatory disease caused by gain-of-function mutations in the gene that codes for STING. Patients produce too much type 1 IFN causing abnormal inflammation throughout the body, especially in the skin, blood vessels, and lungs.
172
Q
Cytosolic DNA sensors
- Stimulator of interferon genes (…)-associated vasculopathy with onset in infancy (SAVI) is an autoinflammatory disease caused by gain-of-function mutations in the gene that codes for …. Patients produce too much type 1 IFN causing abnormal inflammation throughout the body, especially in the skin, blood vessels, and lungs.
A
- Stimulator of interferon genes (STING)-associated vasculopathy with onset in infancy (SAVI) is an autoinflammatory disease caused by gain-of-function mutations in the gene that codes for STING. Patients produce too much type 1 IFN causing abnormal inflammation throughout the body, especially in the skin, blood vessels, and lungs.
174
Q
Acute Phase Response
- Acute phase proteins are mainly produced by the …
- Induced by cytokines such as TNF, IL-6 and IL-1 during infection and inflammation
- Acute phase proteins can activate complement and induce opsonisation/phagocytosis
- Raised erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are characteristic of an acute phase response and are used clinically to detect inflammation
A
- Acute phase proteins are mainly produced by the liver
- Induced by cytokines such as TNF, IL-6 and IL-1 during infection and inflammation
- Acute phase proteins can activate complement and induce opsonisation/phagocytosis
- Raised erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are characteristic of an acute phase response and are used clinically to detect inflammation
175
Q
Acute Phase Response
- Acute phase proteins are mainly produced by the …
- Induced by … such as TNF, IL-6 and IL-1 during infection and inflammation
- Acute phase proteins can activate complement and induce opsonisation/phagocytosis
- Raised erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are characteristic of an acute phase response and are used clinically to detect inflammation
A
- Acute phase proteins are mainly produced by the liver
- Induced by cytokines such as TNF, IL-6 and IL-1 during infection and inflammation
- Acute phase proteins can activate complement and induce opsonisation/phagocytosis
- Raised erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are characteristic of an acute phase response and are used clinically to detect inflammation
176
Q
Acute Phase Response
- Acute phase proteins are mainly produced by the …
- Induced by cytokines such as TNF, IL-6 and IL-1 during infection and inflammation
- Acute phase proteins can activate … and induce opsonisation/phagocytosis
- Raised erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are characteristic of an acute phase response and are used clinically to detect inflammation
A
- Acute phase proteins are mainly produced by the liver
- Induced by cytokines such as TNF, IL-6 and IL-1 during infection and inflammation
- Acute phase proteins can activate complement and induce opsonisation/phagocytosis
- Raised erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are characteristic of an acute phase response and are used clinically to detect inflammation
177
Q
Acute Phase Response
- Acute phase proteins are mainly produced by the liver
- Induced by cytokines such as …, IL-6 and IL-1 during infection and inflammation
- Acute phase proteins can activate complement and induce opsonisation/phagocytosis
- Raised … sedimentation rate (…) and C-reactive protein (CRP) are characteristic of an acute phase response and are used clinically to detect inflammation
A
- Acute phase proteins are mainly produced by the liver
- Induced by cytokines such as TNF, IL-6 and IL-1 during infection and inflammation
- Acute phase proteins can activate complement and induce opsonisation/phagocytosis
- Raised erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are characteristic of an acute phase response and are used clinically to detect inflammation
178
Q
Acute Phase Response
- Acute phase proteins are mainly produced by the liver
- Induced by cytokines such as TNF, IL-.. and IL-.. during infection and inflammation
- Acute phase proteins can activate complement and induce …/…
- Raised erythrocyte sedimentation rate (ESR) and C-… protein (…) are characteristic of an acute phase response and are used clinically to detect inflammation
A
- Acute phase proteins are mainly produced by the liver
- Induced by cytokines such as TNF, IL-6 and IL-1 during infection and inflammation
- Acute phase proteins can activate complement and induce opsonisation/phagocytosis
- Raised erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are characteristic of an acute phase response and are used clinically to detect inflammation
