4 - Antibodies Flashcards
What is an antibody?
A protein produced in response to a foreign molecule (antigen) and can bind specifically to that antigen. They are a class of proteins called immunoglobulins.
What does isotype refer to?
Immunoglobulin structures that are present in all members of a species (e.g., the kappa and lambda light chains, the different heavy chains, the immunoglobulin classes and sub-classes).
What does affinity mean?
A measure of the strength of binding between a single binding site of an antibody and its antigen.
What does avidity mean?
The overall strength of binding between antibody and antigen, taking into account the number of binding sites on the antibody and the number of sites on the antigen (antigenic determinants or epitopes) that can be bound.
Basic antibody structure
Y shaped
2 heavy chains in the centre
2 light chains on the OUTSIDE at the top of the heavy chains.
All connected by disulphide bonds at the middle of the Y.
(2 bonds between the heavy chains, 1 between each heavy and light chain)
Constant regions and variable regions (on the top ends)
What is the antigen binding site?
Relatively large, approximately flat surface with undulations, and is made from the 3 hypervariable regions within V domains that form the complementarity determining regions (CDR’s).
The affinity for antigen binding comes from many non-covalent interactions, each of which individually is relatively weak.
These interactions are made up of hydrogen bonds, ionic bonds, hydrophobic interactions, and van der Waals interactions.
How many classes of antibodies are there in humans?
5…
IgG IgD IgE IgA - dimer IgM - pentameter
What does IgG do?
- Most abundant Ig in blood and tissue
- The most important in defence generally – the other Ig classes have a more specialised role.
- IgG neutralises toxins and viruses.
- Performs a number of functions that are dependent on the nature of its Fc.
- When IgG binds to a bacterium or other infectious agent, macrophages or neutrophils recognise the Fc (they possess Fc receptors) and this leads to phagocytosis (opsonisation).
- In the same situation complement activation can take place promoting phagocytosis or lysis of the bacterium.
- IgG crosses the placenta and, because of its comparatively long halflife, is able to provide protection in the new born child for at least 3 months.
What is the Fc region of an antibody?
The tail region that interacts with cell surface receptors called Fc receptors and proteins in the compliment system.
What are the 4 subclasses of IgG?
IgG1 (70% of total IgG),
IgG2 (20%),
IgG3 (7%),
IgG4 (3%).
For most of these functions, IgG1 and 3 are more active than IgG2 and 4.
Antibodies to bacterial carbohydrates are often IgG2.
What does IgA do?
IgA in the blood occurs in monomer form, but its function there is not well understood.
IgA has an important role in seromucous secretions where it occurs as secretory IgA – a dimer together with J chain and secretory component (SC). SC is added to the molecule during its passage through epithelial cells out into the secretions, and it helps to protect the molecule from degradative enzymes that may be present there (e.g. in the gut).
- Secretory IgA can neutralise toxins.
- By binding to infectious agents it can block their infectivity – often by preventing adherence of the agents to the epithelial cells.
What are the 2 subclasses of IgA?
IgA1 and IgA2.
IgA1 predominates in the blood,
IgA2 is strongly represented in the secretions.
What does IgM do?
IgM is the first Ig to be made following contact with an antigen, and it is active in the blood.
Its five Fab pairs allow it to bind strongly to the surface of bacteria causing agglutination. Like IgG, it is adept at activating complement.
What does IgE do?
Mast cells and basophils have a high affinity receptor for the Fc of IgE (FcεR1).
When IgE that is bound in this way is crosslinked by antigen, degranulation of the cells occurs with release of inflammatory mediators such as histamine.
This process is important in protection against certain parasitic infections, but it can be a nuisance giving rise to allergic diseases such as hay fever or life-threatening anaphylaxis.
What does IgD do?
The least well characterised Ig class
Extremely low concentrations in the blood.
Surface IgD is expressed early in B cell development, and is involved in signalling during B cell development and activation.
