Antigen recognition: B cells and antibody Flashcards
What model does immunological recognition operate through?
Lock and key model
On what scale do antibodies act on?
Less than 1 nm
Can antibodies recognise the same virus after is changes through evolutionary mechanisms?
No
Recognition is incredibly specific
Describe Ehrlich’s side chain theory
Observed that when injected a goat with toxin from a bacteria and then injected the same bacteria, no effect would be observed
Hypothesised the goat made something specific to the organism they injected
Important since the goat had never been exposed to the bacteria before
Ehrlich hypothesised this was because cells with specific shapes on their surface bound to the bacteria, which triggered them to make more of the specific receptor in soluble form
Describe Burnet’s clonal theory
Ehrlich was proven righ by Australian scientist in the 1950s
Instead of one cell with many different receptors, he thought there would be many cells with different receptors
What happens when an antibody closely binds to a specific antigen?
Produces soluble material
Specific cell divides so you have more cells upon secondary infection
How many cells have a specific antibody receptor?
100 cells display one specific receptor
What are the two main goals of adaptive immunity?
Recognising molecular change
Creating large diversity in receptors
What are antibodies?
Protein receptors
Part of a larger protein structure which acts as activators of intracellular mechanisms
What is the shape of an antibody?
Dimer within a dimer
What bonds bind together the heavy and light chains of the antibody?
Disulphide bonds
What is the role of the heavy chain?
Anchors the protein receptor to the cell membrane
Interacts with Fc surface receptors and some proteins of the complement system
Which cells contain Fc receptors?
Follicular dendritic cells
Natural killer cells
Macrophages
Neutrophils
Eosinophils
Basophils
Human platelets
Is the constant region the same for all B cells?
Yes
What is the function of the light chain?
Makes up part of the variable region which acts as an antigen recognition site
What is the complementarity determining region?
Flat surface
Determines how molecules bind to the antibody
Examples of antigen targets of B cells
Proteins
DNA
Sugar
Small molecules
Describe the bonds between proteins and B cell receptors
Bonds form through close apposition of surfaces which have to exactly match
The attraction results from molecules getting close together
Explained through the nature of proteins - commonly make Van der Waals forces
How big is the area that proteins bind to on antibodies?
6 aa by 6 aa
Describe the bonds between DNA and B cell receptors
Charged interactions
Lie on surface
What type of structure does DNA represent?
A rigid structure
Describe the bonds between small molecules and B cell receptors
Penetrate between loops to form tighter binding
What allows for the antibody-antigen interaction to be in equilibrium?
Lack of covalent bonds
Is the antibody-antigen interaction in equilibrium?
In theory they should be
In practice the equilibrium is favoured so far towards the complex formation, it is considered practically irreversible
What governs the equilibrium?
The affinity constant
In the example of antibodies and antigens, the affinity constant is so high that is favours the formation of the complex
What is the affinity constant between antibody and antigens?
10^7
10^8
What happens to the antigen when it attached to the antibody?
It remains attached until it becomes degraded
When does the generation of antibody diversity occur?
During B cell development in the bone marrow
When does the generation of antibody diversity end?
When the B cells have left the bone marrow
How is the diverse population of antibodies produced?
Billions of possible sequences produced by less than 200 genes
How many variable minigenes are there?
40
How many diversity minigenes are there?
27
How many joining minigenes are there?
6
Describe the genetics behind anditbody formation
Genes that encode antibodies are found in one locus
This locus is divided into minigenes coding one part of the final molecule
The minigenes are stitched together to make immunoglobulins
What are the three minigenes coding for antibodies?
Variable
Joining
Diversity
The DNA encoding antigens are the same to the germline
TRUE or FALSE
FALSE
A random process selects one V, J and C gene and stitches them together
The bits in between are thrown away
Features of the VDJ recombination process
Irreversible - can’t use the regions you have thrown away
Allelically exclusive - you rearrange either the maternal or paternal allele and switch off the other allele
Mechanisms of antibody diversity
V, D, J recombination
Imprecise joining of minigenes - recombinational inaccuracies
Independent light and heavy chain combination
Somatic hypermutation
Describe how independent light and heavy chain combination contributes to antibody diversity
Two loci encode the light chain: kappa and lambda
The locus which encodes the light chain is randomly selected
These are chosen randomly and combined with the IgH (heavy chain)
Which enzymes mediate VDJ recombination?
RAG-1
RAG-2
How do RAG enzymes recognise V, D and J segments?
Recombinational signal sequences flanking V, D and J gene segments
What are the two deliberate recombinational inaccuracies which increase antibody diversity?
Enzyme mediated deletion
Addition
What is the source of antibody wastefulness?
VDJ recombinational inaccuracies
If the process of deletion or addition does not happen in 3s, a frameshift mutation causes the protein not to become transcribed
What are mechanisms aimed at combating the wasteful process of recombinational inaccuracies?
Recombination mechanisms
Switching on the alternative allele
