Antibody Structure and Function
• Antibodies, also called immunoglobulins, have a number of different functions:
a. Opsonisation – the binding of an antibody to an antigen at the different epitopes to promote
phagocytosis
b. Complement Activation – antibodies can recruit compliment proteins. These are proteins in
the blood that recognise antibody-antigen binding. When it sees this, there is a mass
recruitment of compliment proteins, which cause the antigen to lyse due to hole created in
the antigen by these compliment proteins. This is a very important immune response
c. Antibody Dependent Cell Mediated Cytotoxicity (ADCC) – Part of the adaptive immune
system and is a cell mediated immune defence. Antigen is destroyed by various cytokines
released by natural killer cells, neutrophils or eosinophils. When antibody-antigen binding
occurs, there is an increase in the aforementioned immune cells which then release
cytokines. Natural killer cells are the main mediator of ADCC
d. Neutralisation of bacteria, viruses and toxins
e. Passive Immunity – antibodies transfer from mother to foetus via placenta
• Antibodies are produced in the plasma of blood
• Antibodies are composed of a combination of four polypeptide chains: 2 x heavy chains and 2 x
light chains
• Antibodies chains are joined to eachother via disulfide bonds (a type of covalent bond)
• Constant region = are the same in ALL antibodies
• Variable region = vary for each antibody (unique to each type)
• Antibodies have two arms in order help bind to pathogens for as long as possible
• The heavy chains determine the antibody isotype (class) and there are 5 x isotypes; mu, delta,
gamma, epsilon and alpha which produce IgM, IgD, IgG, IgE and IgA respectively
• Both IgG and IgA also contain further sub-classes
• The types of light chains are Kappa (more common) and lambda. It is not really known what they do
but it is thought that they help form the antibody binding site.
• Another important concept of antibodies are the Fab and Fc fragments
• Fab fragments = section of antibody that have both heavy and light chains.
 Fab fragment contains variable and hypervariable regions
 Hypervariable region is at tip of Fab fragment and is where antibody-antigen binding occurs
• Fc fragment = only contains heavy chains. It is responsible for binding antibody to host cell and also
the binding and activation of the compliment system mentioned at the beginning of these notes
• Antibody-antigen binding doesn’t utilise covalent bonds, but rather multiple weak forces stabilise
their interaction e.g. electrostatic interactions, hydrophobic interactions, H-bonds and van der Waals
Additional Information
• IgM – only comprises 5-10% of serum Ig
• IgD- only comprises of 0.2% of serum Ig. Its role is still unknown but they don’t think it has any
biological effect
• IgG – Is most common antibody in the blood and comprises 80% of serum. The subtypes IgG1 and
IgG3 are the most prominent
• IgE – has a very low concentration of 0.0002% in the serum. This antibody mediates allergic
response. When allergen (antigen that causes allergic reaction) binds to IgE, cross linking between
another IgE occurs which results in release of histamine and other substances that mediate allergic
response
• IgA – Although only comprises of 10-15% of serum Ig, it is the most synthesised antibody (greatest
daily production). This is because it is found in our mucous membrane (mucosal antibody) and
because it is not a closed system like the blood, it constantly gets excreted and therefore needs to be
constantly synthesised
The Expression Antibodies
• The gene segments that encode for antibodies are V gene segment (V), D gene segment (D), J gene
segment (J) and C gene segments (C) (or can just call them V, D J and C segments)
• the C gene segment codes for the constant regions of an antibody (both the heavy and light chain)
• V, D and J segments encode for the variable region of the antibody, which contains both heavy and
light chains
• V,D,J segments are for heavy chain, whilst light chain only has V and J segments (it has no D
segments)
• The way an antibody variable region is determined is through somatic recombination
• Somatic recombination is the rearrangement of the V,D and J segments
• This process occurs during B-cell maturation
• Whilst the heavy chain of the variable region contains a number of V (48), D (23) and J (6) segments,
the light chain only contains V (41) and J(5) segments and no D segments
Note: the brackets with numbers in it are the number of segments e.g. V (48) = 48 segments of V gene
• When you calculate the possible combinatorial associations of heavy and light chains, you will find
that over 2,500,000 different combinations are possible
Antibody Diversity
• To date, a number of ways to get antibody diversity have been identified, and include:
 Multiple germ-line gene segments
 Combinatorial V-(D)-J joining
 Junctional flexibility
 Somatic hypermutation
 Combinatorial association of light and heavy chains
 Allelic exclusion
Class Switching
• After antigenic stimulation of a B cell, the heavy chain DNA can undergo a further re-arrangement
• This rearrangement is called class switching or isotype switching
• Before binding an antigen, B cells express IgM but after antigen binding, during B cell
differentiation, class switching occurs
• Isotype switching is usually in response
to IL-4 secreted by Helper T cells.
Consequently, they move from the
production of IgM to the formation of
other immunoglobulin isotypes
Primary and Secondary Antibody Response
• In primary exposure to an antigen (the immune-naïve individual) pathogens are detected by T-cells
• Helper T-cells mobilise the B-cells which leads to clonal expansion of B-cells
• In the primary response, the plasma cells initially predominantly produce IgM to bind with and
neutralise the antigen
• There will often be a lag between the first production of IgM and then another lag before the more
specific IgG is produced (see diagram below)
• After this primary exposure, memory B-cells are formed and stored
• Upon secondary exposure to same antigen, a small amount of IgM is produced, but a substantially
greater amount of IgG is released due to the activation of the memory B-cells
• Hence subsequent immune responses are more efficient and effective (explains basis of
immunisation)
• This is also the reason why first exposure to allergens may trigger only a small response, but future
exposure triggers a huge hypersensitivity reaction