Structure and function of individual parts of immunoglobulins. Classes of immunoglobulins, properties and functions. Monoclonal antibodies - preparation, use.

Immunoglobulins are class of proteins produced by B cells and plasma cells. Another term used to refer to Immunoglobulins are antibodies. They serve as line of defense by binding to antigens that correspond to the pathogens that invade our body.

Structure and function of Immunoglobulins

Basic structure :

Antibodies are Y shaped glycoproteins consisting of two small polypeptide chains and two large polypeptide chains. In each respective pair, the polypeptide chains are identical. There are five major classes of immunoglobulins, of which the most abundant in human sera are gamma globulins.

Each short arms of the Y shaped glycoprotein are composed of a pair of chains; light chain and heavy chain held together by disulfide bonds. The two arms are held together by one or more disulfide bonds by the hinge. The chains in immunoglobulins have similar tertiary structure with certain features, most notably "Immunoglobulin folds". Immunoglobulin folds are characterized "beta barrel" antiparallel beta pleated sheets connected by loops of variable and which are held together disulfide bond/s.

The Antibodies can be divided into two fragments;

• Fc: a homogenous portion which can be crystallized
• Antigen binding region: Fab2: this region of the antibody binds to antigens
  • This region consist of heavy and one of two types of light chains.

Basic structure of antibody

Specific features of antibodies

• Hinge regions: this regions provides the characteristic of flexibility that further enables the antibody to bind to the antigen
• In Fab, each heavy chain binds one of two different kinds of light chains; kappa and lambda
• There are five types of heavy chains recognized in humans and each of them are assigned a greek letter
  • Alpha Ά
  • Mu μ
  • Epsilon ε
  • Delta δ
  • Gamma γ

• There are five isotopes of antibodies, they differ from each based on the type of heavy chain present in Fab.
  • Immunoglobulin G : Gamma γ
  • Immunoglobulin A : Alpha Ά
    • they are well known for their role in mucosal immune response
    • their dimeric form is found in bodily fluids like saliva, tears and sweat
    • Secretory component : the attached portion after cleavage of polymeric Ig receptor from dimer IgA
    • Known to works against bacteria particularly against Gram negative and agglutinate viruses
    • Passive immunity for neonates and infants as they are found in breastmilk
    • There are two forms of IgA ->
      • IgA1 and IgA2 can differentiated from each other when compared by the number of disulfide bonds and length of hinge reaction
      • In sera, there are significantly higher levels IgA1 as opposed to mucosal secretion which contain equimolar levels of IgA1 and IgA2
  • Immunoglobulin M : Mu μ
    • On mature or naive B cells, they are expressed as membrane bound
    • They are produced and secreted in plasma cells (activated form of B lymphocytes)
    • Play an important role in primary immune response against bacteria
    • During a inflammatory reaction, IgM is the first antibody isotope secreted
    • They typically exist as a pentameric form as they bind each to each other via the interaction between J chain
    • Each pentameric complex can bind up to 10 antigens
    • These antibodies are released before affinity maturity is developed
    • Lower affinity for antigens than IgG and IgA.
  • Immunoglobulin E : Epsilon ε
  • Immunoglobulin D : Delta δ
    • they are typically found bound to membrane of B cells and expressed in monomeric form.
    • In human sera, it it typical find low levels

• Variable domain : which consists of heterodimers of light chain and heavy chain and the function of this region is antigen binding
  • Two identical variable regions are present in Fab region thus allowing a complete Ig to bind atleast 2 two identical antigens.
  • Antibodies binds to antigens via non covalent bonds such as hydrogen bonds, Van der Waals forces, hydrophobic bonding and electrostatic interactions.
    

    Highlights the variable regions on Antibodies
• Hyper variable regions : Constituents of these region are 100-110 amino acids.
  • Complementary determine region : present on each heavy and light chain, each chain contains three hyper variable regions, they are called that because their structure is complementary to target antigen
  • This feature allows Ig to recognize a wide range of antigens

• Constant domains : the function they serve to provide structural stability
  • In light chains, one constant can be seen.
  • However heavy chains are seen to have 3 - 4.
  • Fc regions are a result of the association between these domains which can elicit different downstream reactions depending on isotype.

Monoclonal antibodies