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BIOL31371 > Important molecules > Flashcards

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)
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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
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3
Q

Caspase 9

A
  • BID cleaved by granzymes
  • Truncated BID disrupts MOM
  • Cytochrome C released
  • Caspase 9 activated
  • DNA cleavage - cell death induced
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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
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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)
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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)

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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)

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8
Q

S1PR1

A

Shingosine 1 phosphate receptor 1

Promotes exit of mature thymocytes toward high concentration of S1P in blood

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9
Q

P-selectin glycoprotein ligand 1

A

Binds P/E selecting, expressed on activated epithelium

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10
Q

CR2

A

Complement receptor 2 (CD21)

Found on marginal zone B-2 B-cells

Respond to circulating complement proteins in the blood

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11
Q

CCL2

A

C-C motif ligand

Directly recruits monocytes

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12
Q

CCR4

A

C-C chemokine receptor type 4

Expressed on Th2 cells

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13
Q

CCR5

A

C-C chemokine receptor type 5

Expressed on Th1 cells and monocytes

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14
Q

CCR6

A

C-C chemokine receptor type 6

Expressed on Th17 cells

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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

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16
Q

CRTH2

A

Chemoattractant receptor-homologous molecule expressed on T helper type 2 (Th2) cells

Expressed on Th2 cells

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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

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18
Q

Granzymes

A

Induce cell death through either to CAD or BID pathways

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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

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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
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21
Q

CD4

A

Cluster of Differentiation 4

Part of the TcR in the CD4 subset of T-cells

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22
Q

CD8

A

Cluster of Differentiation 8

Part of the TcR in the CD4 subset of T-cells

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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

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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

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25
Q

CD28

A

Cluster of Differentiation 28

A costimulatory molecule on T-cells that causes T-cell activation after interaction with CD80/86

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26
Q

CD36

A

Recognises lipids and lipoproteins such as LPS

  • Bacteria
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27
Q

Complement proteins: what are they and what do they do?

A
  • 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
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28
Q

Regulators of the CLA complement pathways: what are they and what do they do?

A
  • 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
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29
Q

CR proteins: what are they, what are the types, what do they bind, what do they do, and what cells are they found in?

A

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
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30
Q

CD27

A

Cluster of Differentiation 27

Costimulatory molecule found on memory cells

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31
Q

CD40

A

Cluster of Differentiation 40

A costimulatory molecule on DCs that causes t-cell activation after interaction with CD40L

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32
Q

CD40L

A

Cluster of Differentiation 40 ligand

A costimulatory molecule on T-cells that causes T-cell activation after interaction with CD40

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33
Q

CD45

A

Cluster of Differentiation 45

Involved in the dephosphorylation of ITAMs

Gets subjected to being in the dSMAC during SMAC formation

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34
Q

CD62L

A

Cluster of Differentiation 62 ligand

Ligand on recent thymic emigrates that promotes movement to secondary lymph tissues for further development

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35
Q

CD80

A

Cluster of Differentiation 80 - B7

A costimulatory molecule on DCs that causes t-cell activation after interaction with CD28

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36
Q

CD86

A

Cluster of Differentiation 86 - B7

A costimulatory molecule on DCs that causes t-cell activation after interaction with CD28

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37
Q

CXCL2

A

Chemokine ligand 2

Produced by cells reacting to IL-17 (Th17 cells)

Promotes neutrophil recruitment

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38
Q

CXCL3

A

Chemokine ligand 3

Expressed on Th1 cells

39
Q

CXCL8

A

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
Q

CXCR1

A

Chemokine receptor type 1

Expressed on neutrophils

Receptor for CXCL8/CXCL2

41
Q

CXCR2

A

Chemokine receptor type 2

Expressed on neutrophils

Receptor for CXCL8/CXCL2

42
Q

CXCR3

A

Expressed on Th1 cells

43
Q

CXCR5

A

Chemokine receptor type 5

Produced by Tfh cells

Chemokine allowing T-cells to move to B-cells

44
Q

IL-1

A

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
Q

IL-1β

A
  • 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
Q

IL-2

A

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
Q

IL-3

A

Produced by Th2 cells

IL-3 (and IL-9) - promote and activate mast cells

Produced by Th1 cells - which promotes monocyte generation

48
Q

IL-4

A

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
Q

IL-5

A

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
Q

IL-6

A

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
Q

IL-7

A

Required for progression into a memory T-cell

Survival signal for ILCs

52
Q

CXCL8

A

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
Q

IL-9

A

Produced by Th2 cells

(With IL-3) - promotes and activates mast cells

54
Q

IL-10

A

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
Q

IL-12

A

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
Q

IL-13

A

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
Q

IL-15

A

Required for progression into a memory T-cell

Survival signal for ILCs

58
Q

IL-17

A

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
Q

IL-17A

A

Produced by ILC3 cells
Produced by Th17 cells

Drives CXCL2 production in stromal cells - results in neutrophil recruitment

60
Q

IL-17F

A

Produced by ILC3 cells
Produced by Th17 cells

Drives CXCL2 production in stromal cells - results in neutrophil recruitment

61
Q

IL-18

A
  • 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
Q

IL-21

A

Promotes the differentiation into Th17 cells through STAT3

Produced by Tfh cells

Inhibits:
* IgG1
* IgG3
* IgA

63
Q

IL-22

A

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
Q

IL-23

A

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
Q

IL-25

A

Produced by and promotes the differentiation into Th17 cells

66
Q

IL-27

A

Promotes T-bet expression through STAT1 signalling along with IFN-γ

67
Q

IL-33

A

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
Q

IgG2a

A

Produced by Tfh1 cells and Tfh17 cells

69
Q

IgG2c

A

Produced by Tfh1 cells

70
Q

IgG3

A

Produced by Tfh17 cells

71
Q

IgE

A

Produced by Tfh2 cells

72
Q

GM-CSF

A

Granulocyte-macrophage colony-stimulating factor

Produced by Th1 cells - stimulates monocyte production in the bone marrow

73
Q

TNF-β

A

Produced during the Th1 response, promotes differentiation into Th1 (positive feedback loop)

74
Q

TNF-α

A

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
Q

LT-α

A

Lymphotoxin α

Produced by CTLs

Help IFNγ to activate macrophages

76
Q

TNF-β

A

Produced during the Th1 response, promotes differentiation into Th1 (positive feedback loop)

77
Q

TGF-β

A

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
Q

IFN-γ

A

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
Q

RA

A

Retinoic acid

Produced by and promotes the differentiation into Tregs

80
Q

BLIMP-1

A

Causes plasma cell differentiation

81
Q

BCL-6

A

Causes memory cell differentiation

82
Q

TSLP

A

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
Q

STAT

A

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
Q

T-bet

A

TF promoting the differentiation into a Th1 cell (and also an ILC1 cell in ILCs)

85
Q

GATA3

A

TF promoting the differentiation into a Th2 cell (and also an ILC2 cell in ILCs)

Expressed in all Tregs

86
Q

RORα/γt

A

TFs promoting the differentiation into a Th17 cell (and also an ILC3 cell in ILCs)

87
Q

Bcl-6

A

TF promoting the differentiation into a Tfh cell (and also an ??? in ILCs), inhibits expression of BLIMP-1 a negative TF regulator

88
Q

Foxp3

A

TF promoting the differentiation into a Treg cell (and also an ILCreg in ILCs)

89
Q

RegIIIγ

A

Anti-microbial proteins

Induced by IL-17

90
Q

RegIIβ

A

Anti-microbial proteins

Induced by IL-17

91
Q

S100A8

A

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
Q

S100A9

A

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
Q

S1PR

A

Sphingosine-1-phosphate receptor

Found on T-cells and B-cells moving to the periphery - promotes the movement towards S1P (in the blood)

BIOL31371 (18 decks)

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