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Hybridoma technology - Essay Example

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Hybridoma technology

This proposal is still being pursued today since antibodies combine specificity (the ability to exquisitely discriminate diverse harmful molecules) and affinity (the ability to tightly lock onto those targets) with the ability to recruit effector functions of the immune system such as antibody- and complement-mediated cytolysis and antibody-dependent cell-mediated cytotoxicity (ADCC).
In the alternative, a "toxic payload" (such as a radioactive element or a plant toxin) attached to the antibody can be accurately delivered to the target. This makes them suitable for homing in on and killing cancer cells, infectious diseases as well as modulating the immune system by binding and inhibiting or enhancing its regulatory molecules thereby curing autoimmune and inflammatory diseases.
White blood cells (B-lymphocytes) of the immune system in higher organisms produce antibodies which are large, glycoprotein molecules. The function of the antibodies is to recognise and attach matter harmful to the organism, thereby marking it out for other components of the immune system to destroy. The organism makes millions of different types of antibodies; each designed to bind a surface feature (the epitope or antigenic determinant) on the foreign body (the antigen). The most common human antibody, IgG, is shaped like the capital letter "Y", IgE, IgD, IgA, IgM are other types of antibodies
Overtime, antibodies have been produced from the serum of animals. Serum contains a cocktail of antibodies (polyclonals), some of which will attach to the antigen. Since when Emil Behring, in1890, published a paper demonstrating that diphtheria antitoxin serum could protect against a lethal dose of diphtheria toxin; antisera has been used to neutralise pathogens in acute disease as well as prophylactically. Antisera is also widely used in vitro as a diagnostic tool to establish and monitor disease. The problem with using antisera for treatment is that it leads to "serum sickness" - basically the patient's immune system reacts against the harmful proteins causing fevers, rashes, joint pains and sometimes life-threatening anaphylactic shock. Also, the serum is a crude extract containing not only the antibodies against the disease-causing pathogen (often at low concentration), but also unrelated antibodies (plus other non-antibody proteins).
In 1975, Csar Milstein and Georges Khler at the Medical Research Council's (MRC) Laboratory of Molecular Biology (LMB) in Cambridge (UK) developed a way to produce "custom-built" antibodies "in vitro" with relative ease. They injected rodent antibody producing cells with immortal tumour cells (myelomas) from the bone marrow of mice to produce a hybridoma. A hybridoma has the cancer's ability to reproduce almost indefinitely, plus the immune cell's ability to make antibodies. Once screened, to isolate the hybridomas producing antibodies of a determined antigen specificity and required affinity - and given the right nutrients - a hybridoma will grow and divide almost indefinitely, mass-producing antibodies of a single type (monoclonals). This resembled a production-line with batch consistency for Ehrlich's "magic bullets". For this breakthrough these scientists (Csar Milstein and Georges Khler) won the Nobel Prize in Medicine in 1984.
Immuno-cytochemical staining has ...Show more

Summary

Hybridoma is a hybrid cell that is produced by injecting a specific antigen into a mouse, collecting an antibody-producing cell from the mouse's spleen, and fusing it with a long-lived cancerous immune cell called a myeloma cell. Individual hybridoma cells are cloned and tested to find those that produce the desired antibody…
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