Antigenic sin
The original antigenic sin ( English : original antigenic sin ) refers to a phenomenon of the antiviral immune response . If individuals who have previously been infected with one virus variant come into contact with a second variant of this virus, there is a strong tendency of the immune system to only form antibodies against epitopes that were already present on the original variant of the virus.
example
If, for example, a two-year-old child becomes infected with an influenza virus for the first time , his immune system will try to generate antibodies against all epitopes of the virus proteins, in particular antigens on the virus surface. If the same person becomes infected again with a variant of the influenza virus years or even decades later, the immune response will preferentially be directed against those epitopes that occur in both virus variants. In contrast, new epitopes, even if they are highly immunogenic, will cause a much weaker antibody response, if any.
Physiological basics
At the cellular level - according to current knowledge - the following scenario takes place: During a primary infection , long-lived memory cells , also called memory cells, emerge from certain activated B cells , which remain in the body to protect against subsequent infections - the so-called " immunological memory ". These memory cells respond to certain epitopes of viral proteins and produce antigen-specific antibodies against them.
It is now possible that the immunity-building surface structures, the antigens of certain viruses, for example influenza or HI viruses, undergo changes in the time between a primary infection and a subsequent secondary infection , a so-called antigen drift . When this happens, the altered virus may still have epitopes that are able to activate memory B cells and cause antibody production .
The antibodies produced by these B lymphocytes will, however, with a high degree of probability bind to the modified, mutated epitopes of the new virus with much lower efficiency and lower affinity . In addition, the already existing antibodies directed against the initial virus seem to suppress the immune responses of naive B cells that have a specificity for the new epitopes present on virus variants - which is the actual sin of antigen inheritance.
It is assumed that these naive B cells are actively inhibited in their development, so that no antibodies can be formed against the new determinants . As a result, this can lead to a weakening of the immune response and a protracted phase of the disease, since a possibly more effective response (against new epitopes) is not provided.
Nevertheless, this reaction pattern can be sensible and useful, since memory B cells, as part of the immunological memory, can react much faster and more efficiently to the renewed viral attack than naive B cells, which in contrast to the immediately responding memory cells only after a few days can provide sufficient amounts of antibodies. In addition, repeated contact with a known antigen increases both the affinity and the amount of the antibodies. This is because the DNA of the B cells is subject to what is known as somatic hypermutation after the primary response , before the cells become antibody-producing plasma cells . Furthermore, a selection takes place by antigens in the germinal centers .
The antigenic sin does not come into play if a previously infected person is exposed to a new virus variant that lacks all epitopes of the original (influenza) virus. There are no already existing antibodies that could bind to the virus, so that the naive B cells can now react.
New insights
Annual booster vaccinations with a current virus strain showed that the induced influenza virus-specific antibodies have the strongest affinity to the virus strain contained in the vaccine and not to the original variant of the virus, as would be expected in the case of the antigenic sin . It is concluded that antigenic sin is not a common phenomenon in normal healthy adults receiving influenza vaccination.
Use in diagnostics
The phenomenon of antigenic sin can in certain cases be useful for the serological diagnosis of viral infections.
Literature & references
- Charles A. Janeway Jr. et al .: Immunobiology: the immune system in health and disease , Garland Publishing, 5th edition, New York 2001, ISBN 0-8153-3642-X and from it the sections:
- Karl Drößler & Diethard Gemsa: Dictionary of Immunology , 3rd edition, Spektrum Akademischer Verlag, Heidelberg, Berlin 2000
Individual evidence
- ^ Charles A. Janeway Jr. et al .: Immunological memory
- ↑ Wrammert et al. (2008): Rapid cloning of high-affinity human monoclonal antibodies against influenza virus. In: Nature Vol. 453 (7195), pp. 667-71. PMID 18449194