B & I - Adaptive Immunity Flashcards

1
Q

does adaptive immunity have memory

A

yes

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2
Q

the _____ response is stronger and more rapid than the _____ response

A

secondary, primary

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3
Q

the affinity of B cells towards antigen (increases/decreases? how/when)

A

increases with time and persistence of antigen

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4
Q

you are born with a massive repertoire of?

A

B and T lymphocytes

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5
Q

what does each lymphocyte represent

A

a different antigen specificity randomly produced by rearrangement of the genes coding for the antigen receptors

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6
Q

what was adaptive immunity first observed in

A

jawless fish

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7
Q

adaptive immunity relies on?

A

the phenomenon of gene rearrangment or recombination - the only genetic locus capable of this

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8
Q

what is the transposase

A

the enzyme that operates on the transposon

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9
Q

the ancient transposases in your genome are called?

A

RAG1 and RAG2 (Recombination Activation Genes)

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10
Q

what does RS stand for

A

Recognition sequences (RS)

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11
Q

where are RS located

A

at the ends of all the Ig and TcR gene segments

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12
Q

what is RS the substrate for

A

RAG1 and RAG2 directed recombination

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13
Q

what is identical in all species that possess adaptive immunity

A

the recognition sequences and RAG1 and RAG2

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14
Q

what does adaptive immunity entail

A

recognition of traits specific to particular pathogens, using a vast array of receptors

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15
Q

what is included in the humoral response of adaptive immunity

A

antibodies defend against infection in body fluids

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16
Q

is adaptive immunity rapid or slow response

A

slow response

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17
Q

what is included in the cell-mediated response of adaptive immunity

A

cytotoxic cells defend against infection in body cells

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18
Q

what are antibodies made of

A

repeated Ig domains

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19
Q

where are Ig domains found

A

in hundreds of different proteins

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20
Q

the Ig protein domain fold is called a

A

B-barrel (of ~110 amino acids)

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21
Q

what are two anti-parallel B-pleated sheets joined in the middle by

A

disulphide bond

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22
Q

the loops at the ends of the strands are not constrained - what does this mean

A

they can vary their amino acid sequences without affecting the stability of the fold

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23
Q

what does the 1st immunisation with antigen result in

A

a rise in antigen specific low affinity IgM in blood

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24
Q

what are the 2nd and 3rd immunisations called

A

boosts

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25
Q

what do 2nd and 3rd immunisations (boosts) do

A

generate a rapid and intense burst of antigen specific high affinity IgG in blood

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26
Q

what are the best vaccines

A

inactive variants of bacteria toxins that rapidly produce high affinity neutralising IgG that binds to the toxin before it binds to their target receptor

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27
Q

where do B cells begin

A

in the bone marrow

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28
Q

where do B cells mature

A

in secondary lymphatic organs such as the spleen and lymph nodes

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29
Q

what do B cells produce and what do they form

A

antibodies and form the humoral (soluble) arm of the adaptive response

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30
Q

what is the B cell antigen receptor

A

a membrane bound IgM molecule

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31
Q

what is the B cell receptor associated with

A

associated with intracellular molecules that transmit an activation signal via phosphorylation

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32
Q

what do T lymphocytes begin as and where do they mature (and what do they mature into) and what do they provide

A

immature lymphocytes that home the Thymus, where they mature into functional T cells and provide cellular adaptive immunity

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33
Q

what is the antigen receptor on T lymphocytes called

A

the T cell receptor (TcR)

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34
Q

what is TcR

A

an immunoglobulin like surface molecule coded for by a separate gene locus

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35
Q

what is TcR associated with and give examples of the two most important ones and what do they do

A

a number of surface molecules and two important ones are CD4 and CD8 that distinguish two functionally different types of T lymphocytes

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36
Q

what does the antibody molecule consist of

A

4 protein chains that are all made up of repeating Ig domains

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37
Q

What are they different types of chains and how many domains are there in each

A

two domains in light chains and 4-5 domains in heavy chains

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38
Q

1H chain is disulphide linked to?

A

1 L chain

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39
Q

2H chains are ?

A

disulphide linked

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40
Q

the Y shaped antibody has two flexible arms - what is located at the top of the two arms and where are these formed

A

antigen binding sites which are formed from the N terminal domains of the L and H chains

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41
Q

the effector region is _________ (invariant/variant) and is bound by __________ and __________

A

invariant, Fc receptors, complement component C1

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42
Q

what two parts is the antibody split into

A

antigen binding and effector

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43
Q

What is the default antibody made by all immature B cells

A

IgM

44
Q

When B cell encounters antigen and activates, it switches to use the ___ _____ to produce an ___ molecule

A

Y gene, IgG

45
Q

what is the rarest class of Ig

A

IgE

46
Q

what does IgE cause

A

atopic allergy

47
Q

what forms does IgM come in

A

membrane bound (monomer) and soluble (pentamer) form

48
Q

what is the membrane form

A

the B-cell receptor

49
Q

how many antigen binding sites does the soluble form have

A

10 antigen binding sites

50
Q

IgM reacts strongly to surfaces such as microbes through ___________

A

avidity binding

51
Q

IgM is good at fixing complement with…

A

complement with 5 Fc regions that bind complement component C1

52
Q

when is there affinity

A

when the sum of the attractive molecular forces at two surfaces exceeds the repulsive forces, there is affinity

(attractive > repulsive)

53
Q

the higher the affinity… (relative to association and dissociation)

A

the fewer molecules it takes per unit volume to associate and to dissociate slowly

54
Q

what does avidity result from

A

multiple affinity contacts

55
Q

in avidity, the strength of binding.. (relative to affinity)

A

can be orders of magnitude higher than the individual affinities

56
Q

antibodies have two identical antigen binding sites so they are

A

bivalent

57
Q

when they bind to a surface using both arms, the binding is governed by

A

avidity - this is much stronger than the affinity of each individual arm

58
Q

soluble IgM molecules are pentameric (5 molecules chained together) and thus

A

exhibit high avidity binding (about 7 orders of magnitude higher than the individual affinity reactions of each site)

59
Q

IgM is ___ affinity, ___ avidity molecules.

A

low, high

60
Q

what do these form (primary surveillance..)

A

the primary surveillance antibody that initially detect infections

61
Q

Ig molecules have different functions depending on the

A

H chain

62
Q

Naive B cells used the __ gene first resulting in a ______ ______ ___ _________ - this is the B cell antigen receptor

A

1) u gene

2) membrane bound IgM molecule

63
Q

after activation, what does the B cell switch to using?

A

a different heavy chain gene - typically Y which produced IgG

64
Q

what is the most abundant antibody in serum

A

IgG

65
Q

which of the Ig activate complement

A

IgG and IgM

66
Q

which of the Ig is secreted at mucosal surfaces

A

IgA

67
Q

which of the Ig is involved in Placental transfer - foetal immunity

A

IgG

68
Q

which of the Ig has high affinity receptor on mast cells

A

IgE

69
Q

which of the Ig have a membrane bound form

A

IgM and IgD

70
Q

Ig in order from most abundant in serum to least abundant

A

IgG > IgA > IgM > IgD > IgE

71
Q

why can an antibody form complementarity to virtually anything?

A

because the potential amino acid diversity at the antigen binding site is vast

72
Q

what is complementarity

A

the measure of how well two molecules interact with each other

73
Q

antibody forms complementarity with an antigen surface if?

A

the sum of the attractive forces exceeds the sum of the repulsive forces

(affinity)

74
Q

what is the antigen binding site of Ig and TcR formed from

A

the 6 protein loop regions that connect the B strands in the Ig variable domain

75
Q

The loop regions are called _________________ __________ ______ and contain massive amino acid diversity caused through the….

A

complementarity determining regions

rearrangement and imprecise joining of germline gene segments in the Ig and TcR locus

76
Q

where is amino acid variation found

A

in CDR, specifically the 3 loops that connect the strands in the 1st domains of the H and L chains

77
Q

3 loops from Vh and Vl juxtapose in the folded protein to form ?

A

a roughly rectangular surface

78
Q

how many identical antigen binding sites are there

A

2

79
Q

what are germ-line genes segmented into?

A

clusters called Variable, Diversity, Joining and Constant regions

80
Q

which chain has no D segments

A

light chain

81
Q

what are RAG1 and RAG2 responsible for and what are they active in

A

responsible for rearrangement and are only active in B and T lymphocytes

82
Q

during recombination, what segments join to what and what happens to intervening DNA

A

D to J and then V to D. Intervening DNA is lost.

83
Q

how does VDJ joining create variation

A

joining is very imprecise so base pairs are changed during repair, this leads to huge variation

84
Q

what does the VDJ region code for

A

CDR3

85
Q

the light chain also rearranges, but since there are no D segments, what segments join?

A

V joins to J

86
Q

imprecise joining results in massive amino acid diversity in the

A

CDR3 loop on the antigen receptor

87
Q

immune system doesn’t know what immune repertoire is required prior to birth, so person is born with millions of different B cell antigen specificities as a result of?

A

random rearrangement of the Ig locus before birth

88
Q

when are individual B cell clones selected to mature

A

when they encounter antigen within germinal centres in lymph nodes

89
Q

where does clonal selection take place

A

within a B cell follicles in your lymph nodes

90
Q

one B cell =

A

one antigen specificity

91
Q

a massive repertoire of naive B cells is generated…

A

stochastically before birth each with a unique B cell receptor

92
Q

where do B cells encounter antigen

A

in lymph nodes

93
Q

antigen expands a small number of B cell clones with ?

A

receptors that weakly bind the antigen

94
Q

what does somatic hypermutation of the Ig gene result in

A

some clones with higher antigen receptor affinity

95
Q

after successive rounds of this, what happens to the mature B cell

A

it becomes a plasma cell which secretes soluble Ig

96
Q

some B cells reside in lymph nodes as long-term _______ ____.

A

memory cells

97
Q

what is the fundamental mechanism behind vaccination

A

affinity maturation

98
Q

MAIN POINT: you have a vast immune B cell repertoire that is

A

generated stochastically before birth

99
Q

MAIN POINT: The Ig and TcR gene loci are segmented into

A

VDJ regions

100
Q

MAIN POINT: what does genetic recombination and imprecise joining of gene segments results in

A

huge diversity in the regions that constitute the antigen binding surface of antibodies and T cell receptors

101
Q

MAIN POINT: what does each naive B cell represent

A

a unique antigen specificity

102
Q

MAIN POINT: antigen drives _______ _________ and ______ in the ____ ____ follicles.

A

clonal selection and expansion

lymph nodes

103
Q

MAIN POINT: persistent antigen and somatic hypermutation results in

A

some B cells with increased affinity towards antigen

104
Q

MAIN POINT: some become antibody secreting…

A

plasma cells

105
Q

MAIN POINT: other cells become long-lived ______ cell that reside in ______ tissue ready to respond rapidly to re-challenge

A

memory

lymphoid

106
Q

MAIN POINT: why does immunisation work

A

affinity maturation