Pharmacology researchers are developing a new antivenom to treat coral snakebites. They immunize horses with snake venom, extract IgG-containing plasma, and then administer the plasma to humans who have been bitten by a coral snake. This therapy neutralizes the venom and improves the patient's symptoms. In order to produce venom-selective antibodies, the researchers select a single venom-specific plasma cell from the immunized horse and induce it to proliferate and produce large amounts of venom-specific IgG. However, they find that the antibody produced by the single plasma cell is less effective at neutralizing the venom than the IgG-containing plasma. A decrease in which of the following best explains the reduced efficacy of the immunoglobulin produced by the single plasma cell?
Monoclonal vs polyclonal antibodies | |
Monoclonal | Polyclonal |
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Exposure to a pathogen or foreign substance (eg, venom) generates innate and adaptive immune responses. The humoral component of the adaptive immune response culminates when activated CD4 cells prompt antigen-specific B cells to undergo somatic hypermutation and class switching, thereby generating a pool of highly specific IgG antibodies that neutralize several different epitopes on the antigen. This is considered a polyclonal response because a number of different clonal plasma cells each produce a specific antibody that targets a different epitope on the antigen.
In contrast, monoclonal antibodies are derived from a single population of plasma cells and bind only a single epitope on the antigen. Naturally occurring monoclonal antibodies are typically seen in pathologic conditions such as plasma cell dyscrasias (eg, multiple myeloma). In the laboratory setting, myeloma cells can be fused to antigen-specific plasma cells to generate a large amount of monoclonal antibody against a particular antigen. However, because monoclonal antibodies bind only a single epitope type on an antigen, they typically generate a less potent immune response than polyclonal antibodies, which bind multiple different epitope types on an antigen.
(Choice A) Affinity is the binding strength of the immunoglobulin for a single epitope on the antigen; the greater the binding strength, the greater the affinity. Each individual type of immunoglobulin in the polyclonal pool will have the same affinity as the monoclonal version of the immunoglobulin.
(Choice B) Avidity is the strength of binding between the entire immunoglobulin and the antigen. Therefore, IgM usually has greater avidity than IgG because IgM binds to up to 10 portions of the antigen while IgG binds to only 2. However, avidity between individual IgG antibodies in a polyclonal versus monoclonal pool is the same.
(Choice D) Valency is the number of epitope binding sites on each antibody. IgM antibodies have 10 valence sites, and IgG antibodies have 2. Each monoclonal and polyclonal IgG antibody has 2 valence sites; valency is no different between these pools.
Educational objective:
Plasma contains polyclonal antibodies, a pool of antibodies that bind different epitopes on an antigen. In contrast, monoclonal antibodies bind a single epitope on an antigen. Polyclonal antibodies are often better at neutralizing complex antigens because they contain antibodies that bind several different epitopes.