ANTIBODY FORMATION AND KINETICS

Antibody formation occurs in response to the presence of a substance perceived by the immune system as foreign. The foreign entity is generically called an antigen. There are a myriad of different antigens that are presented to the immune system. Hence, there are a myriad of antibodies that are formed.

The formation of innumerable antibodies follows the same general pattern. First, the immune system discriminates between host and non-host antigens and reacts only against those not from the host. However, malfunctions occur. An example is rheumatoid arthritis, in which a host response against self-antigens causes the deterioration of bone. Another example is heart disease caused by a host reaction to a heart muscle protein. The immune response is intended for an antigen of a bacterium called Chlamydia, which possess an antigen very similar in structure to the host heart muscle protein.

Another feature of antibody formation is that the production of an antibody can occur even when the host has not "seen" the particular antigen for a long time. In other words, the immune system has a memory for the antigenic response. Finally, the formation of an antibody is a very precise reaction. Alteration of the structure of a protein only slightly can elicit the formation of a different antibody.

The formation of antibody depends upon the processing of the incoming antigen. The processing has three phases. The first phase is the equilibration of an antigen between the inside and outside of cells. Soluble antigens that can dissolve across the cell membranes are able to equilibrate, but more bulky antigens that do not go into solution cannot. The second phase of antigen processing is known as the catabolic decay phase. Here, cells such as macrophages take up the antigen. It is during this phase that the antigen is "presented" to the immune system and the formation of antibody occurs. The final phase of antigen processing is called the immune elimination phase. The coupling between antigen and corresponding antibody occurs, and the complex is degraded. The excess antibody is free to circulate in the bloodstream.

The antibody-producing cell of the immune system is called the lymphocyte or the B cell. The presentation of a protein target stimulates the lymphocyte to divide. This is termed the inductive or lag phase of the primary antibody response. Some of the daughter cells will then produce antibody to the protein target. With time, there will be many daughter lymphocytes and much antibody circulating in the body. During this log or exponential phase, the quantity of antibody increases rapidly.

For a while, the synthesis of antibody is balanced by the breakdown of the antibody, so the concentration of antibody stays the same. This is the plateau or the steady-state phase. Within days or weeks, the production of the antibody slows. After this decline or death phase, a low, baseline concentration may be maintained.

The lymphocytes retain the memory of the target protein. If the antigen target appears, as happens in the second vaccination in a series, the pre-existing, "primed" lymphocytes are stimulated to divide into antibody-producing daughter cells. Thus, the second time around, a great deal more antibody is produced. This primed surge in antibody concentration is the secondary or anamnestic (memory) response. The higher concentration of antibody can be maintained for months, years, or a lifetime.

Another aspect of antibody formation is the change in the class of antibodies that are produced. In the primary response, mainly the IgM class of antibody is made. In the secondary response, IgG, IgE, or IgA types of antibodies are made.

The specificity of an antibody response, while always fairly specific, becomes highly specific in a secondary response. While in a primary response, an antibody may cross-react with antigens similar to the one it was produced in response to, such cross-reaction happens only very rarely in a secondary response. The binding between antibody and antigen becomes tighter in a secondary response as well.