Microbiology and Immunology

WORLD OF MICROBIOLOGY AND IMMUNOLOGY Antibody, monoclonal

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clonal; Antigenic mimicry; Immune stimulation, as a vaccine;

Immunologic therapies; Infection and resistance; Infection

control; Major histocompatibility complex (MHC)

AAntibody formation and kineticsNTIBODY FORMATION AND KINETICS

Antibody formation occurs in response to the presence of a

substance perceived by the immune systemas foreign. The

foreign entity is generically called an antigen. There are a myr-

iad of different antigens that are presented to the immune sys-

tem. 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 anti-

gen of a bacterium called Chlamydia, which possess an anti-

gen very similar in structure to the host heart muscle protein.

Another feature of antibody formation is that the pro-

duction 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 dur-

ing 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 pro-

tein 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 lym-

phocytes 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 pro-

tein. If the antigen target appears, as happens in the second

vaccinationin a series, the pre-existing, “primed” lympho-

cytes are stimulated to divide into antibody-producing daugh-

ter cells. Thus, the second time around, a great deal more

antibody is produced. This primed surge in antibody concen-

tration 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 anti-

genbecomes tighter in a secondary response as well.

See also Antigenic mimicry; History of immunology;

Immunoglobulins and immunoglobulin deficiency syn-

dromes; Laboratory techniques in immunology; Streptococcal

antibody tests

AAntibody, monoclonalNTIBODY, MONOCLONAL

The immune systemof vertebrates help keep the animal

healthy by making millions of different proteins (immunoglob-

ulins) called antibodies to disable antigens (harmful foreign

substances such as toxins or bacteria). Scientists have worked

to develop a method to extract large amounts of specific anti-

bodies from clones (exact copies) of a cell created by fusing

two different natural cells. Those antibodies are called mono-

clonal antibodies.

Antibody research began in the 1930s when the

American pathologist Karl Landsteinerfound that animal anti-

bodies counteract specific antigens and that all antibodies

have similar structures. Research by the American biochemists

Rodney R. Porter (1917–1985) and Gerald M. Edelman

(1929– ) during the 1950s determined antibody structure, and

particularly the active areas of individual antibodies. For their

work they received the 1972 Nobel prize in physiology or

medicine.

By the 1960s, scientists who studied cells needed large

amounts of specific antibodies for their research, but several

problems prevented them from obtaining these antibodies.

Animals can be injected with antigens so they will produce the

desired antibodies, but it is difficult to extract them from

among the many types produced. Attempts to reproduce vari-

ous antibodies in an artificial environment encountered some

complications. Lymphocytes, the type of cell that produces

specific antibodies, are very difficult to grow in the laboratory;

conversely, tumor cells reproduce easily and endlessly, but

make only their own types of antibodies. A bone marrow

tumor called a myeloma interested scientists because it begins

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