ANTIGENS

Antigens are any substances that are capable, under appropriate conditions, of inducing the formation of antibodies and reacting specifi cally with the antibodies so produced. They react with both T-cell recognition receptors and with antibodies. These antigenic molecules may have several antigenic determinants, called epitopes, and each epitope can bind with a specifi c antibody. Thus, a single antigen can bind to many different antibodies with different binding sites.

Some low-molecular-weight molecules called haptens are unable to evoke an immune response but can react with existing antibodies. These molecules need to be coupled to a carrier molecule to be antigenic. 

For some molecules such as drugs, the molecule needs to be conjugated to a carrier. The carrier may be a host protein. The tertiary structure of the molecule as well as the amino acid sequence is important in determining antigenicity. Certain structures such as lipids and DNA are generally poor antigens. 

Most antigens are either thymusdependent or thymus-independent antigens. Thymus-dependent antigens require T-cell participation: Most proteins and foreign red cells are examples of these molecules. Thymus-independent antigens do not require T-cell participation for antibody production. Instead, they directly stimulate specifi c B lymphocytes by crosslinking antigen receptors on the surface of B cells. These molecules produce primarily IgM and IgG2 antibodies and do not stimulate long-lasting memory cells. Most bacterial polysaccharides (found in bacterial cell walls) fall into this category. Certain polysaccharides, such as LPS (lipopolysaccharide), not only induce specifi c B-cell activation but also can act as a polyclonal B-cell stimulant.

ANTIBODY

It consists of a four-chain structure divided into two identical heavy (H) chains with a molecular weight of 25 kDa. Each chain is composed of domains of 110 amino acids and is connected in a loop by a disulfide bond between two cysteine residues in the chain. 

The amino acid N-terminal domains of the heavy and light chains include the antigen-binding site. The amino acids of these variable domains vary between different antibody molecules and are thus known as the variable (V) regions. Most of these differences reside in the hypervariable areas of the molecule and are usually only six to ten amino acid residues in length. When the hypervariable regions in each chain come together along with the counterparts on the other pair of H and L chains, they form the antigen-binding site. This part of the molecule is unique to the molecule and is known as the idiotype determinant. In any individual, 106 to 107 different antibody molecules can be composed from 103 different heavy and light chains of the variable regions. The part of the molecule next to the V region is called the constant (C) region made up of one domain in the light chain (C1) and three or four in a heavy chain (CH). A Cl chain may consist of either two kappa (κ) or two lambda (λ) chains but never one of each. Of all the human antibody molecules, approximately 60%, are κ chains and 40% contain λ chains. Although there are no known differences in the functional properties of κ and λ chains, there are several different types of the CH domain. These differences are refl ected in determining the class (isotype) of the antibody and thereby the physiological function of a particular antibody molecule.

The IgM molecule is the oldest class of immunoglobulins, and it is a large molecule consisting of fi ve basic units held together by a J chain. The major role IgM plays is the intravascular neutralization of organisms, especially viruses. The reason for this important physiological role is that it contains fi ve complement-binding sites, resulting in excellent complement activation. This activation permits the segment removal of antigen–antibody complement complexes via complement receptors on phagocytic cells or complement-mediated lysis of the organism. However, in contrast to the IgG molecule, it has relatively low affi nity binding to the antigen in question. Second, because of its size, it does not usually penetrate into tissues. In contrast, IgG is a smaller molecule that penetrates easily into tissues. There are four major classes of IgG: IgG1 and IgG3 activate complement effi ciently and clear most protein antigens, including the removal of microorganisms by phagocytic cells. 

In contrast, IgG2 and IgG4 react mostly with carbohydrate antigens and are relatively poor opsonins. This is the only molecule that crosses the placenta to provide immune protection to the neonate.