What is another word for an immunoglobulin?
Antibody
How many heavy chains exist in an immunoglobulin?
2
How many domains are in a heavy chain of an immunoglobulin?
4, 3 constant and one variable
How many domains are in a light chain?
2, 1 constant and 1 variable
What are the two types of light chain?
lambda and kappa
Roughly how many aa in light chain?
215
Roughly how many aa in heavy chain?
450
Roughly how many aa in each domain?
105/110
How many disulphide bonds between heavy chains?
Variable! xxx
Constant heavy genes are encoded by how many classes of gene?
5 –> alpha, Mu, gamma, delta, epsilon
What are the different type of immunoglobin based on their heavy?
IgM IgG IgA IgE IgD
In what way are immunoglobulin ‘bi-functional’?
- Vl and Vh regions recognise antigens
- The rest of molecule determines the biological activity, e.g. what cell it binds
Can immunoglobulin activate complement?
Yes
If you digest an immunoglobulin with papain what do you get?
Fab (fragment antigen binding) fragments
How many hypervariable regions do Vl and Vh contain?
3 CDR regions
On each arm of immunoglobulin how many CDRs are there?
6
Roughly how many amino acids long is each CDR?
5-10
Are CDRs in native immunoglobulins spatially or linearly very close?
Spatial, they are not close in the denatured polypeptide
How many aa does the average the immunoglobulin ‘groove’ accommodate?
10 at most
What is an epitope?
The region of the antigen recognised and bound by the antibody.
Are epitopes
a) linear
b) discontinuous
c) either
epitopes can be either, primarily however they are discontinuous
What is a multivalent antigen?
Antigen contains different epitopes
Multivalent antigen with the same epitope are rare in protein antigens but common in WHAT?
Glycan antigens. One antibody type will bind multiple times.
All epitopes and antibodies bind with the same affinity. True or False.
False
What are monoclonal antibodies?
Antibodies that are all the same amino acids.
What are polyclonal antibodies?
Antibodies made against an antigen that are a sum of different antibodies against lots of different epitopes.
Are antibody/epitope interactions
a) covalent
b) non-covalent
non-covalent. High affinity is therefore achieved by precise shape complimentary for close interaction.
Why do people try to get monoclonal antibodies?
they are very specific and so can be used in theraputics
Why do you humanisie mouse antibodies?
In humans they will be recognised as foreign unless humanised. This step is not require these das as you engineer what you want.
How many types of IgG are there?
4, IgG1, IgG2, IgG3, IgG4
IgG1, IgG2a, IgG2b, IgG3
C1q binding to antibodies trigger what?
complement cascade
Which antibodies has good specificity for C1q?
IgG3
Which antibodies can fix complement?
IgM, IgG3
Which antibody is pentameric?
IgM
How many constant heavy chain domains does IgM have?
4
What is J chain?
A small protein required for polymerisation of IgM and IgA
What are two configuration that a IgM pentamer can exist in?
Star configuration
or staple configuration where you get flexibility between c2 and c3 so all binding sites are on one surface
What is the first antibody to be made after a pathogen is met?
IgM
What is the second antibody to be made after a pathogen is met?
IgD
Which immunoglobulin exists as a dimer with a J chain and a secretory component?
IgA
What is the major antibody in the gut?
IgA
What is the function of the secretory component in the IgA dimer?
Protects the immunoglobulin and makes it more stable. It is also part of the receptor used for translocating it from the inside to outside.
What receptor does IgA bind to initiate transcytosis from basolateral membrane to apical membrane of epithelial cell.
poly-immunoglobulin receptor.
This receptor gets cleaved and a part of it remains bound to the IgA in the lumen
What are subclasses IgA?
IgA1, IgA2
Which immunoglobulin is involved in allegoric reactions?
IgE
What is the receptor for IgE on mast cells called?
FCepsilon
What does antibody crosslinking on mast cells cause?
Signal reduction and the mast cell, which is full of granules, to release mediators such as histamine and other substances that mediate allergic reactions.
What is the general term for receptors that bind immunoglobulins?
Fc receptors
FCgamma receptor 1 binds WHAT?
IgG1 and IgG3
What do Fc receptors on phagocytes trigger?
phagocytosis (up take and destruction of antigen coated pathogens)
There are some activating an inhibitory Fc receptors. What domain do the inhibitory receptors contain?
ITIM (immunoreceptor tyrosine based inhibitory motif) domain on the cytoplasmic side
Fc receptors are often
a) homodimer
b) heterodimer
heterodimer.
alpha and gamma chains for example
What is the net affinity of a polyclonal antibody defined by?
The sum of all the antibody’s affinity for the different epitopes
