Copyright 2005 - AntibodyStation.

Basic Antibody Biology

Antibodies are a class of immunological proteins (immunoglobulins) produced by B-cells, and are antigen-specific.

An antigen is defined as a substance that can be bound by an antibody molecule through its antigen-binding sites, also called epitopes. (see Epitopes below)

Many substances can, and are known to be antigenic.

Antigenic substances:

- Proteins

- Nucleic acids: DNA, RNA

- Carbohydrates or sugar groups

- Lipids

- Small Chemical Groups

- Peptides (10-15 amino acids long)

Thus antibodies can bind almost any repertoire of antigens, including chemicals and things B-cells have never encountered before! (we will discuss how this is possible later...)

Large Molecules, such as proteins and large complexes such as bacteria and viruses usually have multiple sites for antibody binding. On a given protein, more than 2 antibodies are thus capable of binding.

Epitopes

Epitopes are each site on an antigen that an antibody can bind to, and are also known as antigenic determinants. Epitopes can be:

1) Conformational -( in which the antibody recognizes the secondary structure of the molecule, ie the secondary structure of the protein)

2) Linear-

A) in which the antibody binds to a determinant in the denatured protein only (ie the antibody recognizes the primary amino acid sequence of the protein).  

B) in which the antibody binds to the determinant in both the denatured protein and the native protein.

3) Neoantigenic - which is an epitope which is not present in the native protein but becomes an epitope after the protein is cleaved by a protease (epitope is exposed by the protein being digested)

What Cells Produce Antibodies?

B-cells produce antibodies in response to infections, to identify and neutralize foreign objects such as bacteria and viruses, and are thus important contributors to adaptive immunity.

Self versus Non-self?

If Antibodies recognize almost anything why don't they attack my own body?

One's body has pre-selected and eliminated during development every single cell that recognizes and produces antibodies against one's self or "self" proteins/molecules.  This process is flawed or becomes flawed later in life and manifests as auto-immunity, where the body attacks itself.

How Can One Produce Antibodies (By Artificially Inducing Them)?

Injection of a foreign antigen into a mouse or rabbit induces activation of the immune system and leads to the production of antibodies specific for the injected protein. The foreign antigen is thus termed an "immunogen".

Small molecules such as chemical groups and peptides are not immunogenic. That is if you inject them into a rabbit, they will not usually produce antibodies against them. 

To make antibodies against small molecules such as chemicals and peptides, they must be coupled to a large protein to form a HAPTEN - CARRIER complex.

Anigens are substances that bind to antibodies through antigen-binding sites. Not all antigenic substances are immunogenic!

Structure of an Antibody

An antibody is composed of 2 Heavy Chains (IgH-Chains or Immunoglobulin Heavy, immuno for immune - globulin meaning protein) and 2 Light Chains (IgL-Chains). Disulfide bonds hold these 4 chains together. See figure 1 below.,

Figure 1. Diagram of an antibody binding to antigen. The light chains are situated on the peripheries and are smaller (thus lighter!). The heavy chains are the 2 inner chains. Notice that both chains contain a black region, this is called the variable region.  This is called "variable", because "every" B-cell (practically every B-cell: except clones) produces a different variable region, and thus allows for the amazing ability for B-cells to produce antibodies for almost every chemical, protein, lipid, nucleic acid, and substance known to man.

The chains consist of Domains (think of this as lego blocks), where there are:

Constant Domains or C Domains (these are the same from antibody to antibody - compare this to variable domains)

Heavy chains have: CH1, CH2, and CH3.

Light chains have CL

and there are:

Variable Domains or V Domains (these vary from one antibody to another - and thus permit differences in antibody properties ie one binds to sugars and another to proteins). Sequencing of a Great Number of Antidodies showed that the first 100-110 amino acid residues of the variable domain are diferent for different antibodies.

VH  for Heavy Chains

VL for Light Chains

Domains are each 110 amino acids long and contain 2 cysteine residues forming a disulfide link loop of about 60 amino acid residues.

The VH and VL domains come together and form the antigen-binding site or pocket, the black region which contacts the antigen in figure 1 above.

Functions of Antibodies in the Body

The immune system has a major role in the body, which is to defend against infection.  Bacteria and viruses enter through or across the skin epithelium.  These locations include but are not limited to the respiratory tract, the digestive system, and the urogenital tract, or through injuries in the skin surface.

To deal with different pathogens, and different sites of infection, the body has at its arsenal various antibody TYPES which it can use.

Types of Antibodies:

IgM antibody isotype - Mainly found in the BLOOD.

IgA antibody isotype - Secreted across epithelial surfaces into the lumen of the gut, intestines, and mammary gland.

This is an important antibody as humans can secrete from 5 - 15 grams of IgA antibody per day!

IgG antibody isotype - Is an antibody which is transported across the placenta into the bloodstream of the fetus.

IgG is also able to neutralize toxins and prevent infections by blocking bacterial and viral entry into cells.

IgM antibody isotype - is involved in complement fixation reaction.

IgE antibody isotype - is involved in ALLERGIC reactions.

 

Copyright 2005 - 2007 - AntibodyStation.