- The ‘foot’ (bottom) of the antibody is known as the Fc fragment - binds to cells, binds to complement = effector function (kills or removes antigen)
- The top (antigen binding) is the Fab fragment
- Chains are held together with disulphide binds
- Associated molecules allow intracellular signalling
- Normally 3X constant heavy chain domains per chain and a hinge region (except μ and ε which have 4 and no hinge region)
Classes of Immunoglobulins
The five primary classes of immunoglobulins are IgG, IgM, IgA, IgD and IgE, distinguished by the type of heavy chain found in the molecule.
- IgG - gamma-chains
- IgMs - mu-chains
- IgAs - alpha-chains
- IgEs - epsilon-chains
- IgDs - delta-chains.
Differences in heavy chain polypeptides allow different types of immune responses. The differences are found primarily in the Fc fragment. There are only two main types of light chains: kappa (κ) and lambda (λ), and any antibody can have any combination of these 2 (variation).
- Gamma chains
- 70-85% of Ig in human serum.
- secondary immune response
- only class that can cross the placenta - protection of the newborn during first 6 months of life
- principle antibody used in immunological research and clinical diagnostics
- 21 day half life
- Hinge region (allows it to make Y and T shapes - increasing chance of being able to bind to more than one site)
- Fc strongly binds to Fcγ receptor on phagocyte - opsono-phagocytosis
- Activates complement pathway
- Serum = pentamer
- Primary immune responses - first Ig to be synthesised
- complement fixing
- 10% of serum Ig
- also expressed on the plasma membrane of B lymphocytes as a monomer - B cell antigen receptor
- H chains each contain an additional hydrophobic domain for anchoring in the membrane
- Monomers are bound together by disulfide bonds and a joining (J) chain.
- Each of the five monomers = two light chains (either kappa or lambda) and two mu heavy chains.
- heavy chain = one variable and four constant regions (no hinge region)
- can cause cell agglutination as a result of recognition of epitopes on invading microorganisms. This antibody-antigen immune complex is then destroyed by complement fixation or receptor mediated endocytosis by macrophages.
In humans there are four subclasses of IgG: IgG1, IgG2, IgG3 and IgG4. IgG1 and IgG3 activate complement.
- B cell receptor
- <1% of blood serum Ig
- has tail pieces that anchor it across B cell membrane
- forms an antigen specific receptor on mature B cells - consequently has no known effector function (don’t kill antigens, purely a receptor) (IgM as a monomer can also do this)
- Extra rigid central domain
- has the most carbohydrates
- IgE primarily defends against parasitic invasion and is responsible for allergic reactions.
- basophils and tissue mast cells express very high affinity Fc receptors for IgE - mast cells then release histamine
- so high that almost all IgE is bound
- sensitizes (activates) mucosal cells and tissues
- protects against helminth parasites
IgE’s main purpose is to protect against parasites but due to improved sanitation these are no longer a prevalent issue across most of the world. Consequently it is thought that they become over activated and over sensitive while looking for parasites and start reacting to eg pollen and causing allergies.
- Exists in serum in both monomeric (IgA1) and dimeric (IgA2) forms (dimeric when 2 Fcs bind via secretory complex)
- 15% of the total serum Ig.
- 4-7 day half life
- Secretory IgA2 (dimer) = primary defense against some local infections
- Secreted as a dimer in mucous (e.g., saliva, tears)
- prevents passage of foreign substances into the circulatory system
Isotype: class of antibody (IgD, IgM etc)
Allotype: person specific alleles
Idiotype: (hyper) variable region - antibody specificity