Humoral Immunity; Antibodies And The Life Cycle Of B Cells Flashcards
What are the heavy chain domains in antibodies?
Alpha (1-2) Delta Epsilon Gamma (1-4) Meu
What are the different types of light chain domains?
Kappa or lambda
What are the four (general) heavy chain domains in each antibody?
Variable heavy
Constant heavy 1-3
What are the two light (general) chain domains in every antibody?
Variable light
Constant light
What does the constant region of an antibody determine?
Biological activity
What are domains stabilised by?
Sulfite bonds
Where is the hinge region of an antibody?
Between CH1 and CH2
What does the hinge region provide for an antibody?
Flexibility
What promotes antibody-immune cell interaction?
Carbohydrate glycosylation on the CH2 site
What is a fragment?
Combination of two domains
What is the complementarity determining region (CDR)?
Where the antigen and antibody interact
What are the functions of an antibody?
Virus and toxin neutralisation
Opsonisation and Antibody Dependant Cellular Phagocytosis (ADCP)
Complement fixing/MAC formation
Opsonisation and Antibody Dependant Cellular Cytotoxicity (ADCC)
What are the classes of antibody?
IgG IgD IgA IgE IgM
Which is the standard antibody?
IgG
What differentiates IgD?
Longer hinge region
What differentiates IgA?
Dimer of antibodies joined by a J chain and covered by a secretory component
What differentiates IgE?
5 domains not four
What differentiates IgM?
Pentimer of antibodies
What is the function of IgM?
Forms immune complexes and fixing complement
What is the function of IgD?
BCR
Indicates mature B cells, only Ab not secreted
What is the function of IgG?
Neutralise toxins and opsonisation
Where is IgA secreted?
Into mucous, tears, saliva and colostrum
What is the function of IgE?
Allergy - anti-parasites
What does class switching allow?
Antibodies to deal with different pathogens
What are the two types of class switching?
Minor and major
Which antibodies carry out minor class switching?
IgM and IgD
What happens in minor class switching?
Differential splicing at the mRNA level
What antibodies take part in major class switching?
IgM -> IgG, IgA and IgE
IgG -> IgA and IgE
What happens in major class switching?
DNA recombination
What does class switching recombination require?
Cytokine signal
Switch regions
AID and DSB repair proteins
Can you reverse class switch recombination?
No
What is the difference between membrane bound and secreted IgGs?
Membrane bound have a cytoplasmic tail and secreted have a tail piece
What causes the difference between membrane bound and secreted IgGs?
Differential splicing - secreted splice the first polyA tail and membrane bound splice at the second
What are the steps in somatic recombination?
VDJ recombination
Tdt nucleotide addition
Somatic hypermutation
Class switching
What are the two stages of the B cell life cycle called?
Antigen independent and dependent stage
What happens in the antigen independent stage?
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
What happens in the antigen dependant stage?
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
Are antibody genes inherited?
No
What codes for CDR3 and what is it?
J or D/J regions
Most variable region of Ab
What are the steps of VJ recombination?
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
What is the function of the L region in front of all the Vk chains?
To the cells know where the protein is going to end up
What happens in VDJ recombination?
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
What do you end up with after VDJ recombination?
IgM or IgD
What are the three VDJ recombination mechanisms?
Recombination signal sequence
‘Turns’
Combinatorial diversity
What are recombination signal sequences?
Conserved sequences upstream or downstream of gene segments
What do VDJ turns consist of?
A heptamer and nonamer with a 12 or 23 bp spacer
Why is junctional diversity bad?
Non-productive rearrangements causes it to be a wasteful process
What is the mechanism of junctional diversity?
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
What is allelic exclusion?
Two copies of each Ig gene
Only one heavy and one light chain allele is expressed
What are the two phases of B cell activation?
T cell independant
T cell dependant
What happens in the T cell independent stage of B cell activation?
Partially activated by the pathogen which causes clonal expansion
Some clones secrete IgM as defence
Others will travel to the thymus
What happens in the T cell dependant pathway of B cell activation?
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
What is the signal transduction pathway?
BCR binding -> activation of tyrosine kinase
What is the germinal centre?
Circular cellular clusters at the periphery of lymph nodes
What happens in affinity maturation?
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
What do T follicular helper cells and follicular dendritic cells do?
Help with affinity maturation
