IMMUNOLOGY

THEORIES OF ANTIBODY PRODUCTION

MANY HYPOTHESIS REGARDING THE ANTIBODY PRODUCTION WERE MADE

There are two theories of antibody production mainly:1.THE INSTRUCTIVE THEORY 2.THE SELECTIVE THEORY

INSTRUCTION VERSUS SELECTION

Precursor of an antibody-forming cell (AFCP) is not precommitted, but has the potential of making any one of a millions of different antibodies. AFCP are precommitted producing antibody of particular specificity. to a

INSTRUCTIVE THEORY These theories postulate that an immunocompetent cell is capable of synthesizing antibodies of any specificity. The antigen encounters an immuno-competent cell and instructs it to produce the complimentary antibody, e.g.-DIRECT TEMPLET THEORY and INDIRECT TEMPLET THEORY.

DIRECT TEMPLET THEORY

These theories were proposed by Breinl & Haurowitz (1930) and Alexander(1931) Mudd(1932). It is proposed by Breinl and Haurowitz in 1930. According to this theory, antigen enters into B cell and act as template for the production of antibody. Since this antibody is produced from antigen, it is specific for antigen. But in reality, the antibody specificity is predetermined before

Burnet and Fenner-1949 proposed this instructive theory to explain the synthesis of antibody as an adaptive protein. According to this theory, antigen enters into B cell and it binds to its DNA and modifies it and forms this modified DNA, antibodies are produced against antigen and it also specific for it. But in nature, there is no need for an antigen to enter into B cell and modify DNA for antibody production because soluble antigen can activate B cell by binding to its cell surface receptor BCR. Because of this reason, this theory also disproved.

INDIRECT TEMPLATE THEORY:

Sir Burnet

SELECTIVE THEORIES
These theories shift the emphasis from the antigen to the immuno-competent cell. They postulate that immuno-competent cells have only a restricted immunological range. The antigen exerts only a selective influence by stimulating the appropriate immuno-competent cell to synthesis an antibody, e.g.Side Chain Theory, Natural Selection Theory\ and Clonal Selection Theory.

SIDE CHAIN THEORY:

It is proposed by Ehrlich in 1897. According to this theory, B cell contains different side chains i.e. antibodies with different specificity. When antigen encounters naive B cell, it can interact with the side chains and select one of the side chains. It inturn activates B cell. Activated B cell then produces antibodies of selected side chain type. But in reality, each B cell possesses only one type of BCR with single specificity. Because of this, this theory disproved

Paul Ehrlich (1854-1915) Germany Nobel price Medicine 1908

he hypothesized that receptors (described as side chains) on the surface of cells could bind specifically to toxins in a "lock-and-key" interaction (Emil Fischer) - and that this binding reaction was the trigger for the production of antibodies. Keypoints
All cells express on their surface sidechains (receptors) that bind toxin. Side chains physiologic function is to to take up food. (A ff) Cell overproduces the partcular sidechain (B) and releases it into the bloodstream (C) Soluble sidechain neutralises toxin (C), or recruits complement (D), agglutinates pathogens (D as membrane-bound form) or even opsonises pathogen (activity only known since 1905)

Explains
all oberserved activities of antibodies (agglutinins, lysins, antitoxins and precipitins and even opsonins) Inducibility (only present in blood is soluble form after immunisation) Specificity (only antibodes to particular pathogen)

Problem

Enough space on a cell for all possible toxins and pathogens?

NATURAL SELECTION THEORY:

This theory is proposed by Jerne in 1955. According to this theory serum will contain antibodies for all antigens and these antibodies are known as natural antibodies. Antibodies for blood group antigen A and B can be given as an example for this theory. But naturally serum will not contain secreted antibodies for specific antigen till it enters host and activates B cell. Because of this valuable reason, this theory also rejected.

Niels Kaj Jerne

This is the present day theory which is also accepted one. Proposed by Burnet in 1957. According this theory, the antigen specificity is predetermined one i.e. B cell is matured with single antigen specificity in bone marrow and B cells with same specificity is referred as B cell clone for a specific specificity. After they matured, they moved to peripheral lymphoid organs. When antigen enters, it moved to peripheral lymphoid organs for activation. In this process, antigen selects a single clone from multiple B cell clone with different specificity. Thus this theory named as clonal selection theory. After a clone is selected by antigen, B cell is activated and proliferated. After proliferation, selected B cells undergo differentiation to form plasma cell and memory B cells for specific antigen. Plasma cells secrete antibodies and they participate in antigen removal and memory cells wait for future antigen encounters. This theory is also practically proved.

CLONAL SELECTION THEORY:

Clonal Selection Theory (Burnet 1957)

Memory
Antigen (Antikrper generierend)
B cell

B cell
receptor Antibody

Monospecific B cells

Plasma cell

clonal expansion

differentiation

o o o o

Each AFCP is pre-committed to produce one antibody (monospecific) Each AFCP carrys membrane-bound immunoglobulin B cell that binds Ag gets expanded and differentiates into AFC Explains - Specifity
- Induciblity - Secondary response - Tolerance to self-antigens (clonal deletion, 1949)

REFRENCES: SPECIAL THANKS TO-Ms.Tanurmi Ghosal (M.Sc.Microbiology

2012 Batch)

Textbook of Microbiology-By R. Vasanthakumari Websites-www. http://biosiva.50webs.org/plasmacell.htm

http://en.wikipedia.org/wiki/File:Burnet_2jpg.jpg
https://www.google.co.in/search?q=clonal http://trove.nla.gov.au/people/508234?c=people

THANK YOU:By-TANURMI GHOSHAL Msc.Microbiology Iind Sem