Antibodies: Introduction

Antibodies

Introduction

Antibodies are globulin proteins (immunoglobulins) that are synthesized in serum and tissue fluids, which react specifically with the antigen that stimulated their production. Three types of globulins are present in the blood: alpha, beta, and gamma.

The antibodies are the gamma globulins. Antibodies are one of the major plasma proteins, and against infection often referred to as “first line of defense”. The most important func-tion of antibodies is to confer protection against microbial pathogens. Antibodies confer protection in the following ways:

1.        They prevent attachment of microbes to mucosal surfaces of the host.

2.        They reduce virulence of microbes by neutralizing toxins and viruses.

3.        They facilitate phagocytosis by opsonization of microbes.

4.        They activate complement, leading to complement-mediated activities against microbes.

Von Behring and Kitasato performed the first experiments that proved the physical existence of antibodies in 1890. They demonstrated that serum obtained from rabbits immunized with tetanus or diphtheria toxins could prevent disease in mice infected with such pathogens. The unknown substance that was present in serum and that provided protection on transfer was named “antitoxin” by Tizzoni and Cattani in 1891. Subsequently, experimental works by Paul Ehrlich and Jules Bordet demonstrated that a protective response could be generated even against whole cells (erythrocytes). The more inclusive term antibody subsequently replaced the term antitoxin.

Tiselius and Kabat accomplished the first successful attempt to identify antibody molecules in 1939. They demon-strated that hyperimmunization increased the concentration of -globulins in serum and that this fraction contained anti-body activity. Because -globulins are large-molecular-weight proteins, it was suggested that further characterization of anti-bodies requires breaking them into smaller and easily handled fragments.

Porter in 1959, succeeded in digesting rabbit immunoglobu-lin G (IgG) with the proteolytic enzyme papain. These produced two distinct fragments: a monovalent fragment with antigen-binding activity, termed Fab (fragment antigen binding) and a second fragment that retained the antibody’s effector functions and crystallized readily into a lattice, termed Fc (fragment crys-tallizable). Edelman and Poulik using a similar method splitted myeloma globulins into two distinct components, which subse-quently were termed heavy (H) and light (L) chains.

The World Health Organization (WHO) in 1964 coined the term “immunoglobulin (Ig)” for the term antibody. The immunoglobulin includes not only antibody globulins but also the cryoglobulins, macroglobulins, and abnormal myeloma proteins. Thus, all antibodies are immunoglobulins but not all immunoglobulins may be antibodies.