Humoral Immunity; Antibodies And The Life Cycle Of B Cells Flashcards

1
Q

What are the heavy chain domains in antibodies?

A
Alpha (1-2)
Delta 
Epsilon
Gamma (1-4) 
Meu
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2
Q

What are the different types of light chain domains?

A

Kappa or lambda

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3
Q

What are the four (general) heavy chain domains in each antibody?

A

Variable heavy

Constant heavy 1-3

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4
Q

What are the two light (general) chain domains in every antibody?

A

Variable light

Constant light

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5
Q

What does the constant region of an antibody determine?

A

Biological activity

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6
Q

What are domains stabilised by?

A

Sulfite bonds

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7
Q

Where is the hinge region of an antibody?

A

Between CH1 and CH2

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8
Q

What does the hinge region provide for an antibody?

A

Flexibility

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9
Q

What promotes antibody-immune cell interaction?

A

Carbohydrate glycosylation on the CH2 site

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10
Q

What is a fragment?

A

Combination of two domains

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11
Q

What is the complementarity determining region (CDR)?

A

Where the antigen and antibody interact

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12
Q

What are the functions of an antibody?

A

Virus and toxin neutralisation
Opsonisation and Antibody Dependant Cellular Phagocytosis (ADCP)
Complement fixing/MAC formation
Opsonisation and Antibody Dependant Cellular Cytotoxicity (ADCC)

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13
Q

What are the classes of antibody?

A
IgG
IgD
IgA
IgE
IgM
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14
Q

Which is the standard antibody?

A

IgG

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15
Q

What differentiates IgD?

A

Longer hinge region

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16
Q

What differentiates IgA?

A

Dimer of antibodies joined by a J chain and covered by a secretory component

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17
Q

What differentiates IgE?

A

5 domains not four

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18
Q

What differentiates IgM?

A

Pentimer of antibodies

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19
Q

What is the function of IgM?

A

Forms immune complexes and fixing complement

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20
Q

What is the function of IgD?

A

BCR

Indicates mature B cells, only Ab not secreted

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21
Q

What is the function of IgG?

A

Neutralise toxins and opsonisation

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22
Q

Where is IgA secreted?

A

Into mucous, tears, saliva and colostrum

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23
Q

What is the function of IgE?

A

Allergy - anti-parasites

24
Q

What does class switching allow?

A

Antibodies to deal with different pathogens

25
Q

What are the two types of class switching?

A

Minor and major

26
Q

Which antibodies carry out minor class switching?

A

IgM and IgD

27
Q

What happens in minor class switching?

A

Differential splicing at the mRNA level

28
Q

What antibodies take part in major class switching?

A

IgM -> IgG, IgA and IgE

IgG -> IgA and IgE

29
Q

What happens in major class switching?

A

DNA recombination

30
Q

What does class switching recombination require?

A

Cytokine signal
Switch regions
AID and DSB repair proteins

31
Q

Can you reverse class switch recombination?

A

No

32
Q

What is the difference between membrane bound and secreted IgGs?

A

Membrane bound have a cytoplasmic tail and secreted have a tail piece

33
Q

What causes the difference between membrane bound and secreted IgGs?

A

Differential splicing - secreted splice the first polyA tail and membrane bound splice at the second

34
Q

What are the steps in somatic recombination?

A

VDJ recombination
Tdt nucleotide addition
Somatic hypermutation
Class switching

35
Q

What are the two stages of the B cell life cycle called?

A

Antigen independent and dependent stage

36
Q

What happens in the antigen independent stage?

A

Stem cell -> pro B cell
Then DJ and VDJ recombination happens
These are expressed with the miu constant region
Variable region is then expressed = pre-B cell that combines with a placeholder chain
Another VJ recombination occurs = immature B cell
Junctional flexibility, P and N nucleotide addition and differential splicing occurs = resting/naive B cell

37
Q

What happens in the antigen dependant stage?

A

Thelper cells activate B cells which then migrate into the germinal centre
Affinity maturation occurs in the germinal centre
Clonal expansion and somatic hypermutation happens in the dark zone
Selection happens in the light zone

38
Q

Are antibody genes inherited?

A

No

39
Q

What codes for CDR3 and what is it?

A

J or D/J regions

Most variable region of Ab

40
Q

What are the steps of VJ recombination?

A

V and J segments are randomly chosen and transcribed into mRNA
Then polyadenylated and RNA spliced to form the mature mRNA
Then translated into a nascent polypeptide which is folded and spliced

41
Q

What is the function of the L region in front of all the Vk chains?

A

To the cells know where the protein is going to end up

42
Q

What happens in VDJ recombination?

A

First the D/J joining occurs
The the V segment is joined to the D/J segment and they are recombined into an RNA transcript
Differential splicing occurs

43
Q

What do you end up with after VDJ recombination?

A

IgM or IgD

44
Q

What are the three VDJ recombination mechanisms?

A

Recombination signal sequence
‘Turns’
Combinatorial diversity

45
Q

What are recombination signal sequences?

A

Conserved sequences upstream or downstream of gene segments

46
Q

What do VDJ turns consist of?

A

A heptamer and nonamer with a 12 or 23 bp spacer

47
Q

Why is junctional diversity bad?

A

Non-productive rearrangements causes it to be a wasteful process

48
Q

What is the mechanism of junctional diversity?

A

V and J turns brought together forming a major hairpin
Major hairpin is cleaved off, leaving only a minor hairpin at the end of gene segments
Enzymes repair and process the minor hairpins, sealing them together

49
Q

What is allelic exclusion?

A

Two copies of each Ig gene

Only one heavy and one light chain allele is expressed

50
Q

What are the two phases of B cell activation?

A

T cell independant

T cell dependant

51
Q

What happens in the T cell independent stage of B cell activation?

A

Partially activated by the pathogen which causes clonal expansion
Some clones secrete IgM as defence
Others will travel to the thymus

52
Q

What happens in the T cell dependant pathway of B cell activation?

A

The T helper cell has to see the same antigen on B cells and dendritic cells for it then to activate the B cell
T helper cells then also produce cytokines to activate the B cell

53
Q

What is the signal transduction pathway?

A

BCR binding -> activation of tyrosine kinase

54
Q

What is the germinal centre?

A

Circular cellular clusters at the periphery of lymph nodes

55
Q

What happens in affinity maturation?

A

Naive B cells have not been exposed to pathogen yet
Somatic mutations in IgV genes
Move into the light zone where they compete for affinity on the FDC

56
Q

What do T follicular helper cells and follicular dendritic cells do?

A

Help with affinity maturation