Humoral Immunity; Antibodies And The Life Cycle Of B Cells

Question 1

What are the heavy chain domains in antibodies?

Answer 1

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

Question 2

What are the different types of light chain domains?

Answer 2

Kappa or lambda

Question 3

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

Answer 3

Variable heavy

Constant heavy 1-3

Question 4

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

Answer 4

Variable light

Constant light

Question 5

What does the constant region of an antibody determine?

Answer 5

Biological activity

Question 6

What are domains stabilised by?

Answer 6

Sulfite bonds

Question 7

Where is the hinge region of an antibody?

Answer 7

Between CH1 and CH2

Question 8

What does the hinge region provide for an antibody?

Answer 8

Flexibility

Question 9

What promotes antibody-immune cell interaction?

Answer 9

Carbohydrate glycosylation on the CH2 site

Question 10

What is a fragment?

Answer 10

Combination of two domains

Question 11

What is the complementarity determining region (CDR)?

Answer 11

Where the antigen and antibody interact

Question 12

What are the functions of an antibody?

Answer 12

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

Question 13

What are the classes of antibody?

Answer 13

IgG
IgD
IgA
IgE
IgM

Question 14

Which is the standard antibody?

Answer 14

IgG

Question 15

What differentiates IgD?

Answer 15

Longer hinge region

Question 16

What differentiates IgA?

Answer 16

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

Question 17

What differentiates IgE?

Answer 17

5 domains not four

Question 18

What differentiates IgM?

Answer 18

Pentimer of antibodies

Question 19

What is the function of IgM?

Answer 19

Forms immune complexes and fixing complement

Question 20

What is the function of IgD?

Answer 20

BCR

Indicates mature B cells, only Ab not secreted

Question 21

What is the function of IgG?

Answer 21

Neutralise toxins and opsonisation

Question 22

Where is IgA secreted?

Answer 22

Into mucous, tears, saliva and colostrum

Question 23

What is the function of IgE?

Answer 23

Allergy - anti-parasites

Question 24

What does class switching allow?

Answer 24

Antibodies to deal with different pathogens

Question 25

What are the two types of class switching?

Answer 25

Minor and major

Question 26

Which antibodies carry out minor class switching?

Answer 26

IgM and IgD

Question 27

What happens in minor class switching?

Answer 27

Differential splicing at the mRNA level

Question 28

What antibodies take part in major class switching?

Answer 28

IgM -> IgG, IgA and IgE | IgG -> IgA and IgE

Question 29

What happens in major class switching?

Answer 29

DNA recombination

Question 30

What does class switching recombination require?

Answer 30

Cytokine signal Switch regions AID and DSB repair proteins

Question 31

Can you reverse class switch recombination?

Answer 31

No

Question 32

What is the difference between membrane bound and secreted IgGs?

Answer 32

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

Question 33

What causes the difference between membrane bound and secreted IgGs?

Answer 33

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

Question 34

What are the steps in somatic recombination?

Answer 34

VDJ recombination Tdt nucleotide addition Somatic hypermutation Class switching

Question 35

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

Answer 35

Antigen independent and dependent stage

Question 36

What happens in the antigen independent stage?

Answer 36

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

Question 37

What happens in the antigen dependant stage?

Answer 37

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

Question 38

Are antibody genes inherited?

Answer 38

No

Question 39

What codes for CDR3 and what is it?

Answer 39

J or D/J regions | Most variable region of Ab

Question 40

What are the steps of VJ recombination?

Answer 40

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

Question 41

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

Answer 41

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

Question 42

What happens in VDJ recombination?

Answer 42

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

Question 43

What do you end up with after VDJ recombination?

Answer 43

IgM or IgD

Question 44

What are the three VDJ recombination mechanisms?

Answer 44

Recombination signal sequence ‘Turns’ Combinatorial diversity

Question 45

What are recombination signal sequences?

Answer 45

Conserved sequences upstream or downstream of gene segments

Question 46

What do VDJ turns consist of?

Answer 46

A heptamer and nonamer with a 12 or 23 bp spacer

Question 47

Why is junctional diversity bad?

Answer 47

Non-productive rearrangements causes it to be a wasteful process

Question 48

What is the mechanism of junctional diversity?

Answer 48

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

Question 49

What is allelic exclusion?

Answer 49

Two copies of each Ig gene | Only one heavy and one light chain allele is expressed

Question 50

What are the two phases of B cell activation?

Answer 50

T cell independant | T cell dependant

Question 51

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

Answer 51

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

Question 52

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

Answer 52

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

Question 53

What is the signal transduction pathway?

Answer 53

BCR binding -> activation of tyrosine kinase

Question 54

What is the germinal centre?

Answer 54

Circular cellular clusters at the periphery of lymph nodes

Question 55

What happens in affinity maturation?

Answer 55

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

Question 56

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

Answer 56

Help with affinity maturation