Important molecules Flashcards
1
Q
Caspase 1
A
- Cleaves pro-IL-1β into IL-1β
- Cleaves pro-IL-18 into IL-18
- Cleaves Gasdermin D, which then enters the plasma membrane and creates a pore for the exit of IL-1β and IL-18 as well as promoting pyroptosis (lytic form of cell death)
2
Q
Caspase 3
A
- Granzymes cleave pro-caspase-3 into caspase 3
- Caspase 3 cleaves ICAD forming CAD
- CAD cleaves DNA - cell death induced
3
Q
Caspase 9
A
- BID cleaved by granzymes
- Truncated BID disrupts MOM
- Cytochrome C released
- Caspase 9 activated
- DNA cleavage - cell death induced
4
Q
E3 ligases: what are they, what do they do, and what are some examples, and what signalling pathways are they involved in?
A
Enzymes that form protein scaffolds to allow for binding of molecules used in signalling pathways
- XIAP (X-linked inhibitor of apoptosis protein) - used in the NLR signalling pathway
- cIAP1 (cellular inhibitor of apoptosis 1) - used in the NLR signalling pathway
- cIAP2 (cellular inhibitor of apoptosis 2) - used in the NLR signalling pathway
- Riplet - used in the TLR signalling pathway
- TRIM25 (Tripartite Motif Containing 25) - used in the TLR signalling pathway
5
Q
Endogenous pyrogens: what does it mean, what are some examples, what systems are affected by them, and what do they cause?
A
Cytokines that promote fever
TNF-α, IL-6, IL-1β, etc
- Liver - acute-phase proteins, c-reactive protein, mannose binding lectin - activation of complement (opsonisation)
- Bone marrow - neutrophil mobilisation - phagocytosis of pathogens
- Hypothalamus - increased body temperature - decreased pathogen replication and increased antigen processing/adaptive immune response
- Fat and muscle - increased metabolism, increasing temperature - decreased pathogen replication and increased antigen processing/adaptive immune response
- Dendritic cells - TNF-α stimulates dendritic migration to lymph nodes and maturation (initiation of adaptive immune response)
6
Q
NFκB
A
Nuclear factor-kappa B - a transcription factor
Produced through PRR signalling pathways - Promotes the production of cytokines and other antibacterial molecules
Produced by signalling induced by the interaction between the TcR and MHC - promotes production of cytokines (ie IL-2)
7
Q
Gasdermin D
A
Cleaved by caspase 1 and then enters the plasma membrane and creates a pore for the exit of IL-1β and IL-18 as well as promoting pyroptosis (lytic form of cell death)
8
Q
S1PR1
A
Shingosine 1 phosphate receptor 1
Promotes exit of mature thymocytes toward high concentration of S1P in blood
9
Q
P-selectin glycoprotein ligand 1
A
Binds P/E selecting, expressed on activated epithelium
10
Q
CR2
A
Complement receptor 2 (CD21)
Found on marginal zone B-2 B-cells
Respond to circulating complement proteins in the blood
11
Q
CCL2
A
C-C motif ligand
Directly recruits monocytes
12
Q
CCR4
A
C-C chemokine receptor type 4
Expressed on Th2 cells
13
Q
CCR5
A
C-C chemokine receptor type 5
Expressed on Th1 cells and monocytes
14
Q
CCR6
A
C-C chemokine receptor type 6
Expressed on Th17 cells
15
Q
CCR7
A
C-C chemokine receptor type 7
Ligand on recent thymic emigrates that promotes movement to secondary lymph tissues for further development
Also on any cells like DCs that are moving to secondary lymph tissues
16
Q
CRTH2
A
Chemoattractant receptor-homologous molecule expressed on T helper type 2 (Th2) cells
Expressed on Th2 cells
17
Q
CTLA-4
A
Cytotoxic T-lymphocyte-associated protein 4
Binds to CD80/86 with higher affinity than CD28, rips t-cells off of dendritic cells
18
Q
Granzymes
A
Induce cell death through either to CAD or BID pathways
19
Q
(i)CAD
A
(Inhibitor of) caspase-activated DNase
Part of the pro-caspase-3 pathway
Cleaves DNA, causing DNA damage and inducing cell death
20
Q
BID
A
BH3 Interacting Domain Death Agonist
Granzymes induce its production
- BID cleaved by granzymes
- Truncated BID disrupts mitochondrial outer membrane
- Cytochrome C released
- Caspase 9 activated
- DNA cleavage - cell death induced
21
Q
CD4
A
Cluster of Differentiation 4
Part of the TcR in the CD4 subset of T-cells
22
Q
CD8
A
Cluster of Differentiation 8
Part of the TcR in the CD4 subset of T-cells
23
Q
CD21
A
Cluster of Differentiation 21 (CR2)
Found on marginal zone B-2 B-cells
Respond to circulating complement proteins in the blood
24
Q
CD25
A
Cluster of Differentiation 25
Part of the TcR in Foxp3+ Tregs, high-affinity IL2R, IL-2 binding causes differentiation into a Foxp3 Treg in the two-step model of Thymus Treg development
25
CD28
Cluster of Differentiation 28
A costimulatory molecule on T-cells that causes T-cell activation after interaction with CD80/86
26
CD36
Recognises lipids and lipoproteins such as LPS
* Bacteria
27
Complement proteins: what are they and what do they do?
* C1q - Binds to pathogen, activation of C1r
* C1r - Cleaves C1s into active form
* C1s - Cleaves C4 and C2
* C4a - Weak mediator of inflammation
* C4b - Binds C2 for C1s cleavage, covalently binds pathogen and opsonises it
* C2a - Cleaves C3 and C5
* C2b - Precursor of vasoactive C2 kinin
* C3a - Promotes inflammation
* C3b - Binds C5 for C2b cleavage, initiates amplification for the alternative pathway, many molecules of it bind to pathogen to opsonise it
* C4b2a - C3 convertase, cleaves C3 into C3a and C3b
* C3bBb - C3 convertase, cleaves C3 into C3a and C3b
* C4b2a3b - C5 convertase, cleaves C5 into C5a and C5b
* C3bBb3b - C5 convertase, cleaves C5 into C5a and C5b
* C5a - Promotes inflammation
* C5b - forms a trimer with C6/C7
* C5b67 - binds C8
* C5b678 - binds C9 molecules and forms the membrane attack complex
28
Regulators of the CLA complement pathways: what are they and what do they do?
* FHRs - Factor-H related proteins, form iC3b (FH/FHL-1, MCP, CR1, etc)
* Properdin - stabilises C3bBb
* Factor I - cleaves C3b into iC3b
* C1inh - inhibits C1
* DAF - Accelerates the decay of C3 and C5 convertases
* CR1 - Accelerates the decay of C3 and C5 convertases
* Clusterin/vitronectin - inhibit the addition of C8 from the C5/6/7 trimer
* CD59 - inhibit C9
29
CR proteins: what are they, what are the types, what do they bind, what do they do, and what cells are they found in?
Complement receptor proteins
* CR1 (CD35) - C3b/C4bi - promotes C3b and C4b decay, stimulates phagocytosis (requires C5a), erythrocyte transport of immune complexes - erythrocytes, macrophages, monocytes, PMN leukocytes, B cells, FDC
* CR2 (CD21) - C3d/iC3b/C3dg - part of B-cell co-receptor, enhances B-cell response to antigens bearing C3d/iC3b/C3dg Epstein-barr virus receptor - marginal zone B-2 B-cells, FDC
* CR3 (CD11b:CD18 heterodimer/Mac-1) - iC3b - stimulates phagocytes - macrophages, monocytes, PMN leukocytes, FDC
* CR4 (CD11c:CD18 heterodimer/gp150, gp95) - iC3b - stimulates phagocytes - macrophages, monocytes, PMN leukocytes, dendritic cells
* CRIg - C3b/iC3b - phagocytosis of circulating pathogens - tissue-resident macrophages, hepatic sinusoid macrophages
30
CD27
Cluster of Differentiation 27
Costimulatory molecule found on memory cells
31
CD40
Cluster of Differentiation 40
A costimulatory molecule on DCs that causes t-cell activation after interaction with CD40L
32
CD40L
Cluster of Differentiation 40 ligand
A costimulatory molecule on T-cells that causes T-cell activation after interaction with CD40
33
CD45
Cluster of Differentiation 45
Involved in the dephosphorylation of ITAMs
Gets subjected to being in the dSMAC during SMAC formation
34
CD62L
Cluster of Differentiation 62 ligand
Ligand on recent thymic emigrates that promotes movement to secondary lymph tissues for further development
35
CD80
Cluster of Differentiation 80 - B7
A costimulatory molecule on DCs that causes t-cell activation after interaction with CD28
36
CD86
Cluster of Differentiation 86 - B7
A costimulatory molecule on DCs that causes t-cell activation after interaction with CD28
37
CXCL2
Chemokine ligand 2
Produced by cells reacting to IL-17 (Th17 cells)
Promotes neutrophil recruitment
38
CXCL3
Chemokine ligand 3
Expressed on Th1 cells
39
CXCL8
Chemokine ligand 8 (IL-8)
Produced by ILC1
Produced by epithelial cells during the type 3 immune response (in response to IL-17A/F)
* Chemotactic factor
* Recruits neutrophils, basophils, and T cells to the site of infection
40
CXCR1
Chemokine receptor type 1
Expressed on neutrophils
Receptor for CXCL8/CXCL2
41
CXCR2
Chemokine receptor type 2
Expressed on neutrophils
Receptor for CXCL8/CXCL2
42
CXCR3
Expressed on Th1 cells
43
CXCR5
Chemokine receptor type 5
Produced by Tfh cells
Chemokine allowing T-cells to move to B-cells
44
IL-1
Produced by and promote the differentiation into Th17 cells
Can stimulate activated and fully differentiated Th17 cells in tissues to produce IL-17/IL-22 independently of TCR stimulation if they are stimulated by it along with IL-23
NFκB activating cytokine
45
IL-1β
* Cleaved from pro-IL-1β into IL-1β by caspase 1
* Secreted using the unconventional protein secretion pathway using Gasdermin D
* Activates vascular endothelium
* Activates lymphocytes
* Local tissue destruction
* Increases access of effector cells
* Causes fever (pyrogenic cytokine)
* Production of IL-6
Promotes Th17 differentiation
Activates ILC3 cells
46
IL-2
Survival signal for ILCs, drive T-cell proliferation
Causes differentiation into a Foxp3 Treg in the two-step model of Thymus Treg development
Promote CD8+ cytotoxic T-cell activity
Synthesised by NFκB, NFAT, and AP-1 acting together on its gene
Produced downstream of the TcR-MHC and CD28-B7 signalling pathways
47
IL-3
Produced by Th2 cells
IL-3 (and IL-9) - promote and activate mast cells
Produced by Th1 cells - which promotes monocyte generation
48
IL-4
Produced during the Th2 response, promotes differentiation into Th2 (positive feedback loop) through STAT6 signalling
Produced by ILC-2 cells and Tfh3 cells
(Along with IL-13) promotes M2-like macrophage differentiation
Induces:
* IgG1
* IgE
Inhibits:
* IgM
* IgG3
* IgG2a
49
IL-5
Produced during the Th2 response
Produced by ILC-2 cells
Can be produced by activated and fully differentiated Th2 cells in tissues independently of TCR stimulation if they are stimulated by TSLP/IL-33
Eosinophil recruitment and activation
* Augments IgA production
50
IL-6
Secreted through the classical secretion pathway using the ER and Golgi
Produced by and promotes the differentiation into Th17 cells
* Lymphocyte activation
* Increased antibody production
* Induces acute-phase protein production
* Causes fever (pyrogenic cytokine)
51
IL-7
Required for progression into a memory T-cell
Survival signal for ILCs
52
CXCL8
Chemokine ligand 8 (IL-8)
Produced by ILC1
Produced by epithelial cells during the type 3 immune response
* Chemotactic factor
* Recruits neutrophils, basophils, and T cells to the site of infection
53
IL-9
Produced by Th2 cells
(With IL-3) - promotes and activates mast cells
54
IL-10
Produced by and promotes the differentiation into Tr1 Tregs
Produced by ILCregs
Produced by Tregs:
Anti-proliferative cytokines - prevents T-cell activation/inhibits activated T-cells
55
IL-12
Secreted through the classical secretion pathway using the ER and Golgi
Produced by Th1 cells -
* Activates NK cells
* Induces the differentiation of CD4 t-cells into Tₕ1 cells through STAT4 signalling
* Can cause IFNγ production by activated and fully differentiated Th1 cells in tissues independently of TCR stimulation if it stimulates T-cells along with IL-18
Produced by M1 macrophages - acts on ILC1/Th1 cells to increase IFNγ production which promotes stabilisation of Th1 cells and promotes naïve CD8+ T cells to become CTLs
56
IL-13
Produced during the Th2 response:
* IL-13 - promotes effects that defend against extracellular parasites - epithelial cell repair, mucus production, smooth muscle contraction (epithelial cell layer is becoming less hospitable)
* (Along with IL-4) promotes M2-like macrophage differentiation
Can be produced by activated and fully differentiated Th2 cells in tissues independently of TCR stimulation if they are stimulated by TSLP/IL-33
Produced by ILC-2 cells and Tfh2 cells
57
IL-15
Required for progression into a memory T-cell
Survival signal for ILCs
58
IL-17
Includes IL-17A,F, etc
Produced by ILC3, Th17, and Tfh17 cells
Produced by activated and fully differentiated Th17 cells in tissues independently of TCR stimulation if they are stimulated by IL-1/IL-23
59
IL-17A
Produced by ILC3 cells
Produced by Th17 cells
Drives CXCL2 production in stromal cells - results in neutrophil recruitment
60
IL-17F
Produced by ILC3 cells
Produced by Th17 cells
Drives CXCL2 production in stromal cells - results in neutrophil recruitment
61
IL-18
* Cleaved from pro-IL-18 into IL-18 by caspase 1
* Secreted using the unconventional protein secretion pathway using Gasdermin D
* Can cause IFNγ production by activated and fully differentiated Th1 cells in tissues independently of TCR stimulation if it stimulates T-cells along with IL-12
Produced by ILC1
NFκB activating cytokine
62
IL-21
Promotes the differentiation into Th17 cells through STAT3
Produced by Tfh cells
Inhibits:
* IgG1
* IgG3
* IgA
63
IL-22
Produced by ILC3 cells
Produced by Th17 cells
Acts on epithelial cells to induce secretion of antimicrobial peptides, reinforce barrier function
Produced by activated and fully differentiated Th17 cells in tissues independently of TCR stimulation if they are stimulated by IL-1/IL-23
64
IL-23
Promotes the differentiation into Th17 cells through STAT3
Activates ILC3 cells
Can stimulate activated and fully differentiated Th17 cells in tissues to produce IL-17/IL-22 independently of TCR stimulation if they are stimulated by it along with IL-1
65
IL-25
Produced by and promotes the differentiation into Th17 cells
66
IL-27
Promotes T-bet expression through STAT1 signalling along with IFN-γ
67
IL-33
DAMP that can be detected by ILC2
Can stimulate activated and fully differentiated Th2 cells in tissues to produce IL-5/IL-13 independently of TCR stimulation if they are stimulated by it along with TSLP
NFκB activating cytokine
68
IgG2a
Produced by Tfh1 cells and Tfh17 cells
69
IgG2c
Produced by Tfh1 cells
70
IgG3
Produced by Tfh17 cells
71
IgE
Produced by Tfh2 cells
72
GM-CSF
Granulocyte-macrophage colony-stimulating factor
Produced by Th1 cells - stimulates monocyte production in the bone marrow
73
TNF-β
Produced during the Th1 response, promotes differentiation into Th1 (positive feedback loop)
74
TNF-α
Tumour necrosis factor α
* Activates vascular endothelium/increases permeability, leading to increased entry of IgG, complement, and cells to tissues and increased fluid drainage to lymph nodes
* Causes fever (pyrogenic cytokine)
* Mobilisation of metabolites metabolites
* Shock
Produced by CTLs - help IFNγ to activate macrophages
Produced by Th1 cells
Produced by ILC-1 cells
75
LT-α
Lymphotoxin α
Produced by CTLs
Help IFNγ to activate macrophages
76
TNF-β
Produced during the Th1 response, promotes differentiation into Th1 (positive feedback loop)
77
TGF-β
Produced by and promotes the differentiation into Th17 cells
Produced by Tregs:
Anti-proliferative cytokines - prevents T-cell activation/inhibits activated T-cells
Induces:
* IgG2b
* IgA
Inhibits:
* IgM
* IgG3
78
IFN-γ
Produced during the Th1 response, promotes differentiation into Th1 (positive feedback loop) along with IL-27
Produced by ILC-1 cells and Tfh1 cells
Can be produced by activated and fully differentiated Th1 cells in tissues independently of TCR stimulation if stimulated by IL-12/IL-18
Produced by CD8+ CTL - activate macrophages, induce MHC I expression, inhibit viral replication, etc
Activates macrophages and CD8+ cytotoxic t-cells - promotes intracellular pathogen killing
Induces:
* IgG2b
* IgA
Inhibits:
* IgM
* IgG3
* IFN-γ and TNF-α during early stages of infection
* IL-12
* IL-18
79
RA
Retinoic acid
Produced by and promotes the differentiation into Tregs
80
BLIMP-1
Causes plasma cell differentiation
81
BCL-6
Causes memory cell differentiation
82
TSLP
Thymic stromal lymphopoietin
STAT TF activating cytokine
DAMP that can be detected by ILC2
Can stimulate activated and fully differentiated Th2 cells in tissues to produce IL-5/IL-13 independently of TCR stimulation if they are stimulated by it along with IL-33
83
STAT
Signal transducer of activation
Different stats cause the differentiation of CD4+ T-cells: t-bet (STAT1/4), GATA3 (STAT5), RORα/γt (STAT3), Foxp3, etc
84
T-bet
TF promoting the differentiation into a Th1 cell (and also an ILC1 cell in ILCs)
85
GATA3
TF promoting the differentiation into a Th2 cell (and also an ILC2 cell in ILCs)
Expressed in all Tregs
86
RORα/γt
TFs promoting the differentiation into a Th17 cell (and also an ILC3 cell in ILCs)
87
Bcl-6
TF promoting the differentiation into a Tfh cell (and also an ??? in ILCs), inhibits expression of BLIMP-1 a negative TF regulator
88
Foxp3
TF promoting the differentiation into a Treg cell (and also an ILCreg in ILCs)
89
RegIIIγ
Anti-microbial proteins
Induced by IL-17
90
RegIIβ
Anti-microbial proteins
Induced by IL-17
91
S100A8
Calgranulin A
Anti-microbial proteins - sequester calcium in the environment along with S100A9 to reduce Ca²⁺ supply for the proliferating microorganism
Induced by IL-17
92
S100A9
Calcium-binding protein A9
Anti-microbial proteins - sequester calcium in the environment along with S100A8 to reduce Ca²⁺ supply for the proliferating microorganism
Induced by IL-17
93
S1PR
Sphingosine-1-phosphate receptor
Found on T-cells and B-cells moving to the periphery - promotes the movement towards S1P (in the blood)
