Blood and Immune: Adaptive immunity, antibodies and your immune repertoire Flashcards
What is adaptive immunity?
Your immunity that has memory. The secondary response is stronger and more rapid than the primary response
Does affinity of B cells towards antigens increase over time and with persistence?
yes
What is persistence of an antigen
antigen is taken up in specialized tissue, lymph nodes, and make germinal centres and lymphoid follicles . They produce lots of progeny that have similar but developing antibody molecules
When is your immune repertoire developed?
before birth (develop as many combinations of antigen binding molecules as possible)(10^11 different antigen binding molecules)
What is on each B and T lymphocyte
Each lymphocyte represents a different antigen specificity randomly produced by rearrangement of the genes coding for the antigen receptors.
are the receptors the same on all B cells
no, each carry an individual receptor that is different from every other B cell
What is a transposases
DNA cutting and repair enzyme
What causes high number of antigen specificities
Gene rearrangement/recombination is
important for the production of the
vast number of antigen specificities
What gene regions use the same mechanism of rearrangment as transposons
Immunoglobulin (Ig) and T cell Receptor (TcR)
Transposase’s in the genome
RAG1 and RAG2 (Recombination Activation Genes)
Where are recognition sequences (RS) found
are located at the ends of all the Ig and TcR gene segments
What is transposase able to do
moved away from the receptor gene enabling it to operate in trans i.e. it can rearrange other genes without affecting its own position in the genome
What are recognition sequences (RS)
These are base pair sequences found at the ends of any gene segments that rearranges – RS are the substrate for RAG1 and RAG2 directed recombination
Are RS palindromic
yes, read in the same direction, 3’ to 5’ or 5’ to 3’
What type of formation do RS form
hairpin formation
What species contain RS and RAG 1 and 2
The Recognition Sequences and RAG1 and RAG2 are identical in all species that possess adaptive immunity
What is the Ig fold
most basic component of a immunoglobulin protein
Where are antibodies formed from?
repeated Ig domains. Ig domains are found in hundreds of different proteins.
What is Ig protein domain fold called
β-barrel
How many amino acids in a β-barrel
~110 amino acids
How is a Ig fold structured
Two antiparallel β-pleated sheets joined in the middle by a disulphide bond
What can the loops at the end of strands in an Ig fold do
not constrained so they can vary their amino acid sequences without affecting the stability of the fold
How many loop regions are in a Ig fold
3
Where is the antigen binding site
the 3 loop regions
How many protein chains are in an antibody
4
What makes up each chain in an antibody
repeating Ig domains
How many domains are in the light chain in an antibody
2
How many domains are in the heavy chain in an antibody
4-5
Size of IgG
150kD
How is a heavy and light chain linked together
through a disulphide bond
How are heavy chains bonded together
disulphide bonds
Are all antibodies immunoglobins
yes
What are at the top of the two “arms” on an antibody
antigen binding sites
What forms the antigen-binding sites
N terminal domains of the L and H chains
can the effector region of an antibody change
no (invariant)
What binds the effector region of an antibody
Fc receptors and complement component C1
why are both the antigen-binding sites identical
because they came from the same B lymphocyre
What domain carries the antigen-binding site
FaB
Number of residues in the light chain
212
Number of residues in the heavy chain
450
What is the default Ig produced by naive B cells
IgM
Types of IgM
It can be membrane bound (monomer) or soluble (pentamer)
What is the name of the membrane bound form of IgM
B-cell antigen receptor (BCR)
How many binding sites does the soluble form of IgM have
10
What causes IgM to react strongly to surfaces such as microbes
avidity binding
What binds 5 IgG molecules together
J chain
Affinity and avidity in IgM
low affinity and high avidity
Relationship between IgM and B lymphocytes
It is a membrane bound receptor on the surface of B cells. As soon as B cell recognises antigen it triggers to produce IgM
What is affinity
When the sum of the attractive forces is greater than the sum of the repulsive forces
fewer molecules
What does a higher affinity mean
Higher affinity means that it takes fewer molecules per unit volume to associate and dissociate slowly.
What is the antibody binding constant
no. of antibody and antigen to give 50% bound as a complex
What is the dissociation constant
is how long the complex to dissociate away before you move away from reactants/equilibrium
What happens when an antibody and antigen come together
(affinity) there is a molecular interaction in the surface which is governed by both repulsive and attractive forces. They come together and stay together for a certain period of time
types of attractive forces between antigen and antibody
electrostatic, sharing electron clouds, hydrophobic, van der waals
What is avidity
Multiple affinity contacts, strength of binding is much greater than the strength of the individual affinities
What two factors govern avidity
the concentration required to get antigen and antibody to come together and also how long it takes the antigen and antibody complex to dissociate away from equilibrium
how many classes of Ig are there
5
What determines the function of different Ig molecules
the genes in its heavy chain
After being activated, what type of Ig does a B cell switch too (due to different heavy chain gene)
IgG
Properties of IgG
activates complement, can be transferred through the placenta
Properties of IgM
Activates complement, has a membrane-bound form
Properties of IgA
Secreted at mucosal surfaces
Properties of IgD
Has a membrane-bound form
Properties of IgE
Has a high affinity receptor on mast cells
Which types of Ig molecules bind with avidity
IgM and IgG bind with avidity, exposing Fc region allowing them to bind well with complement
Where is IgA found
in secretory sites like tears, saliva and breast milk - babies need IgA from mother which is long lasting in gut (gives them strong gut immunity)
Which two types of Ig are membrane-bound
IgM and IgD
What is complementarity
a measure of how well to molecules interact with each other
When is complementarity formed between an antigen and an antibody
if the sum of the attractive forces exceeds of the sum of the repulsive forces
When does affinity increase?
when the sum of the attractive forces exceeds the sum of repulsive molecular forces
Why are there so many different antibody molecules in the body from a limited amount of genes
somatic hypermutation
What are Complementarity Determining Regions (CDR)
3 regions/loops (that connect the strands in the 1st domains of the Heavy and Light chains ) where amino acids sequences are different between each antibody molecule
Area of the antigen-binding site
800-1000 square Angstroms
How many identical antigen-binding sites are there
2
Names of clusters that germlines are separated into
Variable, diversity, joining, constant
What segment does a light chain NOT contain
D (diversity) segment
What is responsible for rearrangement in B and T lymphocytes
RAG1 and RAG2 (Recombination activation gene)
Most variable region in Ig molecules
CDR3
What is the order of rearrangement in heavy chains
D to J, V to D
Why is joining imprecise in the recombination of the Ig locus
so that base pairs are changed during repair. This leads to huge variation at the VDJ join ( results in massive amino acid diversity in the CDR3 loop on the antigen receptor)
Number of variable (V) segments in H-chains
100
Number of diversity (D) segments in H-chains
27
Number of joining (J) segments in H-chains
6
Number of variable (V) segments in L-chains
35
Number of joining (J) segments in L-chains
5
What is clonal selection
The process by which an antigen selectively binds to and activates only those lymphocytes bearing receptors specific for the antigen. The selected lymphocytes proliferate and differentiate into a clone of effector cells and a clone of memory cells specific for the stimulating antigen.
What happens if a B cell encounters the antigen it has an affinity for
it produces plasma cells which produce highly affinity soluble IgG
Where are B cells found
B cells are in lymph nodes throughout the body
What is within the lymphoid follicle
germinal centres where B cell that has encountered pathogen is undergoing somatic hypermutation - generating B cell progeny which will become high affinity cells
What does stochastically mean
occurring randomly
When is the massive repertoire of naïve B cells generated stochastically
before birth each with a unique B cell Receptor
What does somatic hypermutation result in
B cell clones with higher antigen receptor affinity
What is a plasma cell
A fully differentiated B cell that produces a single type of antibody.
What allows vaccinations to work
affinity maturation
The function of memory cells
they reside in lymphoid tissue ready to respond rapidly to re-challenge.
