Antibodies Flashcards
What are the receptors that recognise pathogens?
PRRs - pathogen recognition receptors
MHC
TCR
BCR
What do PRRs recognise?
PAMP - pathogen associated molecular patterns
DAMP - damage associated molecular patterns
How many genes encode for PRRs?
100+
Not very polymorphic since there is little variation in PAMPs and DAMPs between individuals
What do MHC recognise?
Peptides on classical alpha beta T cells
How many genes encode for MHC?
12
Inherit 3 MHC I and 3 MHC II genes from mother and father respectively
What do TCRs recognise?
Peptides linked to MHC
How many genes encode for TCRs?
Millions
Very polymorphic
Same with BCRs
What do BCRs recognise?
Antigens
How many genes encode for BCRs?
Millions
Very polymorphic
Where are PRRs found?
On surface, intracellularly and secreted
What brings about polymorphism in MHC?
Each protein is encoded for individually, so there is increased polymorphism
How does the large genetic variation in TCRs and BCRs arise?
Genetic recombination
Describe an antibody molecule
Tetramer
Consists of two heavy chains bound together via disulphide bonds
Consists of two light chains bound to the heavy chains via disulphide bonds
Can be split into variable and constant region
Where is the constant region?
The constant region is the larger part of the antibody molecule
Determined mostly by the genetic sequence of heavy chain
The light chain can also have variability in the constant chain however, and classify into Kappa and Lambda
How heavy are the heavy chains?
50 kD
How heavy are the light chains?
25 kD
What is the role of the constant region?
Determines the class of antibody
IgM, IgG, IgA, IgD
What is the role of the variable region?
Binds to specific epitopes on antigens
What is the hypervariable region?
Area on the variable region that has increased variability. Binds to the epitopes of antigens
Also known as conplementarity determining regions
What is another name for the hypervariable region?
Complementarity determining region
How does variability arise?
Via genetic recombination
What are the 3 gene segments on antibodies that give rise to variability?
V, D and J segments
How many genes form the J, V and D segments in the heavy chain?
V= 40 D= 27 J= 6
What does J, V and D stand for?
Variable, diversity and joining
How many genes form J and V regions of the Kappa light chain?
V = 40 J= 5
How does an antibody look like in terms of the V, D and J regions? `
Constant region - J - D - V
What controls genetic recombination?
A series of enzymes encoded by RAG-1 and RAG-2
What does RAG stand for?
Recombination-activating genes
How do RAGs recognise where to recombine?
Via recombination signalling sequences
RSSs
What are RSSs?
Recombination signalling sequences
Sequences of nucelotides found at the end of V, D and J sequences that signal the RAGs to start recombination
What is an example of an enzyme encoded by RAG?
Recombinase enzyme is involved with V, D, J recombination
Additional mechanisms that increase variability of antibody molecules?
Recombinational inaccuracies DIfferent splicing in D J regions Make soluble or transmembrane form Class switching Additional nucleotides added via N-region diversity
What processes happen in antibody diversification but not TCR diversification?
Class switching
Only make transmembrane version
Somatic hypermutation
What two types of recombination events happen in the maturation of antibodies?
VDG recombination
Class switching
What is class switching?
Process by which antibody switches its class whilst remaining equally antigen-specific
What determines the class of an antibody?
Its constant region
How do antibodies switch class?
With the help of T helper cells
Switch depending on the type of antibody required to combat the pathogen
How is class switching different from VDJ recombination?
Uses different enzymes
Uses class switching signals instead of recombination signal sequences
What classes do the antibodies switch to?
From IgM and IgD
To IgA, IgG and IgE
What is the consequence of recombination?
From less than 200 genes (V (40) D (27) and J (6)) we can make millions of possible combinations
In the heavy chain, the possibility of different variations is 40276 = 6480
Since some antibodies can have the exact same heavy region but different light chain Kappa regions, the variabiliy increases
Possibility of different variations in Kappa light chain is 40*5 = 200
Therefore the possibility of different variations is 200*6480 = over 1 million
Increases if add possibility of Delta light chain combinations
What are the properties of IgG?
Only antigen that can pass through the placenta
phagocytosis and complement activation
What are the functions of IgM?
Together with IgD, make up BCR of naive B cells
One of the first antibodies found in the site of infection
Complement activation and agglutination
WHat two antibodies make up the BCR of naive B cells?
IgM and IgD
What is the function of IgE?
Triggers inflammatory mediators from mast cells/ basophils
What two antibodies form polymers?
IgM and IgA
How is IgA found in the circulation?
When IgA dimerises
Is bound to secretory components that transport secretory IgA to mucosal surfaces
Link together in the ring via J-chains
How do the IgA antibodies link together?
Via J-chains
How is IgM found in the circulation?
As a monomer
What shape does a IgM polymer make when it dimerises?
A pentameric ring
How big is the pentameric ring of IgM polymers?
1 million Da
Can’t escape circulation in polymeric form
Where does genetic recombination of antigen happen?
In the variable region
