6.3.2.3: Antibody Functions
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Learning Objectives
- Differentiate among affinity, avidity, and cross-reactivity in antibodies
Differentiated plasma cells are crucial players in the humoral immunity response. The antibodies they secrete are particularly significant against extracellular pathogens and toxins. Once secreted, antibodies circulate freely and act independently of plasma cells. Sometimes, antibodies can be transferred from one individual to another. For instance, a person who has recently produced a successful immune response against a particular disease agent can donate blood to a non-immune recipient, confering temporary immunity through antibodies in the donor’s blood serum. This phenomenon, called passive immunity, also occurs naturally during breastfeeding, which makes breastfed infants highly resistant to infections during the first few months of life.
Antibodies coat extracellular pathogens and neutralize them by blocking key sites on the pathogen that enhance their infectivity, such as receptors that “dock” pathogens on host cells. Antibody neutralization can prevent pathogens from entering and infecting host cells, as opposed to the cytotoxic T-cell-mediated approach of killing cells that are already infected to prevent progression of an established infection. The neutralized antibody-coated pathogens can then be filtered by the spleen and eliminated in urine or feces.
Antibodies also mark pathogens for destruction by phagocytic cells, such as macrophages or neutrophils, because they are highly attracted to macromolecules complexed with antibodies. Phagocytic enhancement by antibodies is called opsonization. In another process, complement fixation, IgM and IgG in serum bind to antigens, providing docking sites onto which sequential complement proteins can bind. The combination of antibodies and complement enhances opsonization even further, promoting rapid clearing of pathogens.
Affinity, avidity, and cross reactivity
Not all antibodies bind with the same strength, specificity, and stability. In fact, antibodies exhibit different affinities (attraction) depending on the molecular complementarity between antigen and antibody molecules. An antibody with a higher affinity for a particular antigen would bind more strongly and stably. It would be expected to present a more challenging defense against the pathogen corresponding to the specific antigen.
The term avidity describes binding by antibody classes that are secreted as joined, multivalent structures (such as IgM and IgA). Although avidity measures the strength of binding, just as affinity does, the avidity is not simply the sum of the affinities of the antibodies in a multimeric structure. The avidity depends on the number of identical binding sites on the antigen being detected, as well as other physical and chemical factors. Typically, multimeric antibodies, such as pentameric IgM, are classified as having lower affinity than monomeric antibodies, but high avidity. Essentially, the fact that multimeric antibodies can bind many antigens simultaneously balances their slightly-lower-binding strength for each antibody/antigen interaction.
Antibodies secreted after binding to one epitope on an antigen may exhibit cross reactivity for the same or similar epitopes on different antigens. Cross reactivity occurs when an antibody binds not to the antigen that elicited its synthesis and secretion, but to a different antigen. Because an epitope corresponds to such a small region (the surface area of about four to six amino acids), it is possible for different macromolecules to exhibit the same molecular identities and orientations over short regions.
Cross reactivity can be beneficial if an individual develops immunity to several related pathogens despite having been exposed to or vaccinated against only one of them. For instance, antibody cross reactivity may occur against the similar surface structures of various Gram-negative bacteria. Conversely, antibodies raised against pathogenic molecular components that resemble self molecules may incorrectly mark host cells for destruction, causing autoimmune damage. Patients who develop systemic lupus erythematosus (SLE) commonly exhibit antibodies that react with their own DNA. These antibodies may have been initially raised against the nucleic acid of microorganisms, but later cross-reacted with self-antigens. This phenomenon is also called molecular mimicry.
Contributions and Attributions
- OpenStax College, Biology. October 17, 2013. Provided by : OpenStax CNX. Located at : http://cnx.org/content/m44823/latest...ol11448/latest . License : CC BY: Attribution
- immunoglobulin. Provided by : Wiktionary. Located at : en.wiktionary.org/wiki/immunoglobulin . License : CC BY-SA: Attribution-ShareAlike
- epitope. Provided by : Wiktionary. Located at : en.wiktionary.org/wiki/epitope . License : CC BY-SA: Attribution-ShareAlike
- antigen. Provided by : Wiktionary. Located at : en.wiktionary.org/wiki/antigen . License : CC BY-SA: Attribution-ShareAlike
- B cell. Provided by : Wiktionary. Located at : en.wiktionary.org/wiki/B_cell . License : CC BY-SA: Attribution-ShareAlike
- OpenStax College, Antibodies. October 17, 2013. Provided by : OpenStax CNX. Located at : http://cnx.org/content/m44823/latest...e_42_03_01.jpg . License : CC BY: Attribution
- OpenStax College, Antibodies. October 17, 2013. Provided by : OpenStax CNX. Located at : http://cnx.org/content/m44823/latest...e_42_03_02.jpg . License : CC BY: Attribution
- OpenStax College, Biology. October 17, 2013. Provided by : OpenStax CNX. Located at : http://cnx.org/content/m44823/latest...ol11448/latest . License : CC BY: Attribution
- OpenStax College, Biology. October 23, 2013. Provided by : OpenStax CNX. Located at : http://cnx.org/content/m44823/latest...ol11448/latest . License : CC BY: Attribution
- avidity. Provided by : Wiktionary. Located at : en.wiktionary.org/wiki/avidity . License : CC BY-SA: Attribution-ShareAlike
- affinity. Provided by : Wiktionary. Located at : en.wiktionary.org/wiki/affinity . License : CC BY-SA: Attribution-ShareAlike
- OpenStax College, Antibodies. October 17, 2013. Provided by : OpenStax CNX. Located at : http://cnx.org/content/m44823/latest...e_42_03_01.jpg . License : CC BY: Attribution
- OpenStax College, Antibodies. October 17, 2013. Provided by : OpenStax CNX. Located at : http://cnx.org/content/m44823/latest...e_42_03_02.jpg . License : CC BY: Attribution
- OpenStax College, Antibodies. October 17, 2013. Provided by : OpenStax CNX. Located at : http://cnx.org/content/m44823/latest...e_42_03_03.jpg . License : CC BY: Attribution
- OpenStax College, Antibodies. October 17, 2013. Provided by : OpenStax CNX. Located at : http://cnx.org/content/m44823/latest...e_42_03_04.jpg . License : CC BY: Attribution
Key Points
- Antibodies are produced by plasma cells, but, once secreted, can act independently against extracellular pathogen and toxins.
- Antibodies bind to specific antigens on pathogens; this binding can inhibit pathogen infectivity by blocking key extracellular sites, such as receptors involved in host cell entry.
- Antibodies can also induce the innate immune response to destroy a pathogen, by activating phagocytes such as macrophages or neutrophils, which are attracted to antibody-bound cells.
- Affinity describes how strongly a single antibody binds a given antigen, while avidity describes the binding of a multimeric antibody to multiple antigens.
- A multimeric antibody may have individual arms with low affinity, but have high overall avidity due to synergistic effects between binding sites.
- Cross reactivity occurs when an antibody binds to a different-but-similar antigen than the one for which it was raised; this can increase pathogen resistance or result in an autoimmune reaction.
Key Terms
- avidity : the measure of the synergism of the strength individual interactions between proteins
- affinity : the attraction between an antibody and an antigen