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Basic Immunology- Module 1 > Chapter 4 > Flashcards

Chapter 4 Flashcards

1
Q

What is the fundamental difference between TCR and BCRs?

A

BCRs can recognise free antigen whereas TCRs can only respond to peptide presented by MHC

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2
Q

What is the benefit of TCR vs BCR receptors?

A

TCRs can respond to antigens confined within cells

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3
Q

What is the major difference between MHC classes I and II?

A

MHC class I present peptides from intracellular sources whereas MHC class II- extracellular

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4
Q

What is the structure of a TCR?

A

transmembrane molecule composed of 2 disulfide-linked chains a and b

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5
Q

How are the alpha and beta chains of the TCR organised?

A

folded into 2 domains- one with invarian structure and one with high dgree of variability- like Fab fragment

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6
Q

How many hypervariable regions does each variable region of the TCR have?

A

3

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7
Q

What is the name of the hypervariable regions found on TCRs?

A

CDR- complementarity determining regions

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8
Q

What is the function of the CDRs?

A

contain the amino acids which make contact with the pMHC

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9
Q

What is found on the cytoplasmic tail of CD4 and CD8?

A

bound to tyrosine kinase Lck

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10
Q

What is the function of Lck?

A

initiates signal transduction cascase following encounter of T cell with antigen

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11
Q

What is the structure of CD4?

A

single-chain polypeptide containing 4 Ig-like domains which form an extended rod

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12
Q

What is the structure of CD8?

A

disulfide-liinked heterodimer of a and b chains which each have a single Ig-like domain contnected to a glyosylated polypeptide

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13
Q

What is the ab TCR known as?

A

TCR1

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14
Q

Where are yd TCRs mainly found?

A

epithelial-rich tissues

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15
Q

What is the difference between T-cells expressing ab TCRs and yd TCRs?

A

yd do not require MHC for antigen detection and often do not express MHC co-receptors (CD4 and CD8)

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16
Q

What is the function of CD4 and CD8?

A

act as coreceptors for TCRs

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17
Q

Why may yd T-cells be involved in regulation of the immune system?

A

recognise molecules that appear on activated T cells

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18
Q

What complex is associated with the TCR?

A

CD3

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19
Q

What is the function of CD3?

A

relays signal to the interior of the T-cell to act on ligation of antigen

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20
Q

What is the structure of the CD3 molecule?

A

a ye dimer; a x-x dimer and de dimer

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21
Q

what is the function of the fourth hypervariable region of beta chain of a TCR?

A

binding site for superantigens (not pMHC)

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22
Q

What is found in the cytoplasmic domains of CD3 peptide chains?

A

immunoreceptor tyrosine-based activation motifs

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23
Q

What are ITAMs linked to?

A

src protein tyrosine kinases

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24
Q

What happens to the ITAMs on the CD3 compex when TCR meets p-MHC?

A

phosphorylated by the Lck tyrosine kinase on CD4/CD8– recruitment of proteins—etc

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25
Q

Why would a cell express non-classical MHC class I molecules?

A

cell stress of DNA damage

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26
Q

What type of PRR are particularly suited to inducing the expression of type I interferons?

A

ones situated within the intracellular compartments- TLR3, TLR7-9, RIG-like helicases

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27
Q

What is one of the downstream consequences of interferon secretion?

A

cessation of protein synthesis and therefore downregulation of MHC molecules

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28
Q

what do inhibitory receptors on NK cells have on their cytoplasmic tail?

A

ITIMs- immunoreceptor tyrosin-kinase inhibitory motifs

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29
Q

What is the function of ITIMs?

A

recruit phosphatases eg SHP-1 which antagonise signal transudction

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30
Q

Give an example of a protein found on activating receptors on NK cells

A

DAP-12 containing ITAMs

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31
Q

Give an example of receptors on NK cells?

A

killer immunoglobulin-like receptors (KIRs); CTLRs

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32
Q

Give examples of CTLRs that NK cells use

A

CD94/NKG2 family

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33
Q

How does CD94/NKG2A inhibit NK response?

A

interacts with an invariant MHC-related molecule HLA-E

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34
Q

What is surface expression of HLA-E dependent on?

A

proper synthesis of HLA-A, B and C- as bind leader protein sequences on these molecules

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35
Q

When are MICA and MICB upregulated?

A

cell stress and damage

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36
Q

What CTLR recognises MICA and MICB?

A

NKG2D/NKG2D

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37
Q

What is the function of all natural cytotoxicity receptors found on NK cells?

A

activating

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38
Q

Give an example of an Fc activating receptor on NK cells?

A

CD16

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39
Q

What causes CD16 to be activated?

A

IgG bound to antigen present on a target cell

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40
Q

How does heat shock cause missing self?

A

heat shock proteins eg HSP-60 displace HLA-E which CD94/NKG2 can no longer bind to

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41
Q

How are NK cells involved in tumour surveillance?

A

checkpoint kinases can upregulate NK receptor ligands

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42
Q

What are class I MHC molecules bound to?

A

beta2-microglobulin

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43
Q

How is the largest part of hte heavy chain of class I MHC organised?

A

into 3 globular domains-a1, a2 and a3

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44
Q

What links the a1 and a2 somains in MHC-I?

A

beta pleated sheet

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45
Q

What type of protein are MHC?

A

glycoprotein

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46
Q

What is the MHC-II made up of?

A

an alpha and beta polypeptide chain

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47
Q

What are the class III genes found in the MHC chromosome region?

A

A variety of genes that directly/indirectly relate to immune defence functions

48
Q

Give examples of class III genes?

A

Complement components C4 isotopes, TNF, lynphotoxin

49
Q

Why would so many immune response related genes be clustered within a relatively small region of the genome?

A

Perhaps as location of a gene within chromatin can influence transcriptional activity, so proximity means genes are expressed at similar levels

50
Q

What is the difference between genetic variation in non-classical and classical MHC genes?

A

No classical are far less polymorphic and are often invariant

51
Q

What is the function of non classical MHC I molecules?

A

Form structures similar to class I molecules and present non petite antigens or invariant peptides which are involved in monitoring overall cell stress levels

52
Q

How have highly polymorphic MHC genes developed?

A

Probably through pathogen driven section to form new alleles that may offer increased fitness for the individual

53
Q

Are the beta2 microgobulins attaches to MHC polymorphic?

A

No-invariant

54
Q

How do the multiple allelic forms of MHC develop?

A

Point mutations, recombination, homologous but unequal crossing over, gene conversion

55
Q

What is the gene expression of inherited MHC alleles?

A

Codominant expression

56
Q

Which cells express class II MHC?

A

B cells, dendritic cells, macrophages, thymic epithelium

57
Q

What chromosome are classical MHC genes found on?

A

6

58
Q

What gene are non-classical MHC molecules found on?

A

1

59
Q

Give an example of a non classical MHC molecule

A

CD1

60
Q

What is the function of CD1?

A

Presents lipids or glycolipipds to T-cells

61
Q

How many CD1 subsets do humans express?

A

4

62
Q

Which TLRs are expressed on the cell surface?

A

TLR1, 2, 4, 5 and 6

63
Q

What is the extracellular structure of the TLRs?

A

leucine rich repeats facing towards the interior of the protein forming a hydrophobic core with variable regions facing outwards to form beta-sheets

64
Q

What is the shape of the TLRs described as ?

A

solenoid-like

65
Q

Why is the overall shape of the TLR a horseshoe?

A

beta sheets are more tightly packed than the leucine rhc repeats forcing hte beta sheets into a cruve

66
Q

What conformation does ligand-induced dimerization of adjacent TLRs result in?

A

m-shaped conformation with TLRs interacting at their C-termini

67
Q

What is the strcture of LPS?

A

glycolipid with a hydrophobic lipid A region attached to a carbohydrate chain

68
Q

What segment of LPS is critical for TLR4/MD2 complex activation?

A

Lipid A segment

69
Q

Which region of LPS is responsible for the majority of inflammatory activity of LPS?

A

Lipid A region

70
Q

What is the site of interaction between adjacent LPS and MD2 molecules known as?

A

Dimerisation interface

71
Q

What type of molecule is TLR2 important in the recognition of?

A

Microbial lipopeptides

72
Q

Which bacteria are mice at risk of with a deficiency of TLR2?

A

S. Pneumoniae and M.tuberculosis

73
Q

What is the structure of bacterial lipoproteins?

A

Glycerol backbone with 2/3 attached acyl (fatty acid) chains

74
Q

What type of lipoprotein do gram negative bacteria possess?

A

Tri-acylated lipoproteins

75
Q

What type of lipoprotein do gram positive bacteria and mycoplasma possess?

A

Diacylated

76
Q

What type of bacteria does the TLR2/TRL1 complex respond to?

A

Tri-acylated -gram negatives

77
Q

What type of bacteria does the TLR2/TLR6 complex respond to?

A

Diacylated- gram positive and mycobacterium

78
Q

What is found on the border between the central and C-termini of TLR1 and TLR2 which is different to the norm?

A

Border is milder into ligand-binding pockets, lined with hydrophobic residues

79
Q

What is the difference between the C-terminal ligand binding pocket in TLR1 and TLR6?

A

Pocket in TLR6 is partially blocked by the bulky side chains of 2 phenylalanine residues reducing the pocket size by half

80
Q

What does MAL stand for?

A

MyD88 adaptor-like protein

81
Q

What structure is responsible for activating NFkB?

A

Myddosome

82
Q

What constitutes the Myddosome?

A

6 molecules of MyD88, 4 molecules of IRAK4 and 4 molecules of IRAK2

83
Q

What is the structure of the TIR domain?

A

Central beta sheet of 4/5 parallel beta strands with 5 a helixes connected to the edges of the sheet by a series of loops

84
Q

What loop in the TIR domain plays a critical role in signal transduction?

A

BB loop (beta B strand) and alpha B helix

85
Q

What is the function of MAL in TLR4 activation?

A

Acts as a bridging molecule to stabilise the TLR4-MyD88 interaction

86
Q

What does TRAM stand for?

A

TRIF related adaptor molecule

87
Q

What does activation of TRIF cause?

A

Activation of IRF3 and expression of interferon genes

88
Q

When is TRAM recruited to TLR4?

A

Only after receptor mediated endocytosis

89
Q

What does the recruitment of TRAM only after receptor mediated endocytosis suggest?

A

Acidic environment of endosome causes a conformational change in the receptor

90
Q

What is different about the BB loop of TLR3 as compared to other TLRs?

A

Contains an alanine instead of a proline-mutation of which changes specificity of TLR3 from TRIF to MAL/MyD88

91
Q

What type of interaction drives the myddosome?

A

Death domain-death domain

92
Q

What is the shape of the myddosome?

A

Helical 3-layered complex

93
Q

What segment of LPS is critical for TLR4/MD2 complex activation?

A

Lipid A segment

94
Q

Which region of LPS is responsible for the majority of inflammatory activity of LPS?

A

Lipid A region

95
Q

What is the site of interaction between adjacent LPS and MD2 molecules known as?

A

Dimerisation interface

96
Q

What type of molecule is TLR2 important in the recognition of?

A

Microbial lipopeptides

97
Q

Which bacteria are mice at risk of with a deficiency of TLR2?

A

S. Pneumoniae and M.tuberculosis

98
Q

What is the structure of bacterial lipoproteins?

A

Glycerol backbone with 2/3 attached acyl (fatty acid) chains

99
Q

What type of lipoprotein do gram negative bacteria possess?

A

Tri-acylated lipoproteins

100
Q

What type of lipoprotein do gram positive bacteria and mycoplasma possess?

A

Diacylated

101
Q

What type of bacteria does the TLR2/TRL1 complex respond to?

A

Tri-acylated -gram negatives

102
Q

What type of bacteria does the TLR2/TLR6 complex respond to?

A

Diacylated- gram positive and mycobacterium

103
Q

What is found on the border between the central and C-termini of TLR1 and TLR2 which is different to the norm?

A

Border is milder into ligand-binding pockets, lined with hydrophobic residues

104
Q

What is the difference between the C-terminal ligand binding pocket in TLR1 and TLR6?

A

Pocket in TLR6 is partially blocked by the bulky side chains of 2 phenylalanine residues reducing the pocket size by half

105
Q

What does MAL stand for?

A

MyD88 adaptor-like protein

106
Q

What structure is responsible for activating NFkB?

A

Myddosome

107
Q

What constitutes the Myddosome?

A

6 molecules of MyD88, 4 molecules of IRAK4 and 4 molecules of IRAK2

108
Q

What is the structure of the TIR domain?

A

Central beta sheet of 4/5 parallel beta strands with 5 a helixes connected to the edges of the sheet by a series of loops

109
Q

What loop in the TIR domain plays a critical role in signal transduction?

A

BB loop (beta B strand) and alpha B helix

110
Q

What is the function of MAL in TLR4 activation?

A

Acts as a bridging molecule to stabilise the TLR4-MyD88 interaction

111
Q

What does TRAM stand for?

A

TRIF related adaptor molecule

112
Q

What does activation of TRIF cause?

A

Activation of IRF3 and expression of interferon genes

113
Q

When is TRAM recruited to TLR4?

A

Only after receptor mediated endocytosis

114
Q

What does the recruitment of TRAM only after receptor mediated endocytosis suggest?

A

Acidic environment of endosome causes a conformational change in the receptor

115
Q

What is different about the BB loop of TLR3 as compared to other TLRs?

A

Contains an alanine instead of a proline-mutation of which changes specificity of TLR3 from TRIF to MAL/MyD88

116
Q

What type of interaction drives the myddosome?

A

Death domain-death domain

117
Q

What is the shape of the myddosome?

A

Helical 3-layered complex

Basic Immunology- Module 1 (31 decks)

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