Original antigenic sin
Encyclopedia
Original antigenic sin, also known as the Hoskins effect, refers to the propensity of the body's immune system
to preferentially utilize immunological memory
based on a previous infection
when a second slightly different version, of that foreign entity (e.g. a virus
or bacterium) is encountered. This leaves the immune system "trapped" by the first response it has made to each antigen
, and unable to mount potentially more effective responses during subsequent infections. The phenomenon of original antigenic sin has been described in relation to influenza virus, dengue fever
, human immunodeficiency virus (HIV), and to several other viruses.
This phenomenon was first described in 1960 by Thomas Francis, Jr. in the article "On the Doctrine of Original Antigenic Sin". It is named by analogy to the theological concept of original sin
. According to Thomas Francis who originally described the idea and cited by Richard Krause:
During a primary infection
, long-lived memory B cell
s are generated, which remain in the body, and provide protection from subsequent infections. These memory B cells respond to specific epitopes on the surface of viral proteins in order to produce antigen-specific antibodies, and are able to respond to infection much faster than B cells are able to respond to novel antigens. This effect shortens the amount of time required to clear subsequent infections.
Between primary and secondary infections, or following vaccination
, a virus may undergo antigenic drift
, in which the viral surface proteins (the epitopes) are altered through natural mutation, allowing the virus to escape the immune system. When this happens, the altered virus preferentially reactivates previously activated high-affinity memory B cells and spur antibody production. However, the antibodies produced by these B cells generally ineffectively bind to the altered epitopes. In addition, these antibodies inhibit the activation of lower-affinity naive B cells that would be able to make more effective antibodies to the second virus. This leads to a less effective immune response and recurrent infections may take longer to clear.
Original antigenic sin is of particular importance in the application of vaccines. The specificity and the quality of the immune response is often diminished in individuals who are repeatedly immunized (by vaccination or recurrent infections). However, the impact of antigenic sin on protection has not been well established, and appears to differ with each infectious agent vaccine, geographic location, and age.
.
s for HIV and hepatitis C
based on induction of cytotoxic (CTL) responses. The finding that CTL may be biased by original antigenic sin, may help to explain the limited effectiveness of these vaccines. Viruses like HIV are highly variable and undergo mutation frequently, and thus, due to original antigenic sin, HIV infection induced by viruses that express slightly different epitopes (than those in a viral vaccine) would fail to be controlled by the vaccine. In fact, the vaccine might make the infection even worse, by "trapping" the immune response into the first, ineffective, response it made against the virus.
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
to preferentially utilize immunological memory
Immunity (medical)
Immunity is a biological term that describes a state of having sufficient biological defenses to avoid infection, disease, or other unwanted biological invasion. Immunity involves both specific and non-specific components. The non-specific components act either as barriers or as eliminators of wide...
based on a previous infection
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...
when a second slightly different version, of that foreign entity (e.g. a virus
Virus
A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...
or bacterium) is encountered. This leaves the immune system "trapped" by the first response it has made to each antigen
Antigen
An antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...
, and unable to mount potentially more effective responses during subsequent infections. The phenomenon of original antigenic sin has been described in relation to influenza virus, dengue fever
Dengue fever
Dengue fever , also known as breakbone fever, is an infectious tropical disease caused by the dengue virus. Symptoms include fever, headache, muscle and joint pains, and a characteristic skin rash that is similar to measles...
, human immunodeficiency virus (HIV), and to several other viruses.
This phenomenon was first described in 1960 by Thomas Francis, Jr. in the article "On the Doctrine of Original Antigenic Sin". It is named by analogy to the theological concept of original sin
Original sin
Original sin is, according to a Christian theological doctrine, humanity's state of sin resulting from the Fall of Man. This condition has been characterized in many ways, ranging from something as insignificant as a slight deficiency, or a tendency toward sin yet without collective guilt, referred...
. According to Thomas Francis who originally described the idea and cited by Richard Krause:
"The antibody of childhood is largely a response to dominant antigen of the virus causing the first type A influenza infection of the lifetime. [...] The imprint established by the original virus infection governs the antibody response thereafter. This we have called the Doctrine of the Original Antigenic Sin."
In B cells
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...
, long-lived memory B cell
Memory B cell
Memory B cells are a B cell sub-type that are formed following primary infection.-Primary response, paratopes, and epitopes:In wake of first infection involving a particular antigen, the responding naïve cells proliferate to produce a colony of cells, most of which differentiate into the plasma...
s are generated, which remain in the body, and provide protection from subsequent infections. These memory B cells respond to specific epitopes on the surface of viral proteins in order to produce antigen-specific antibodies, and are able to respond to infection much faster than B cells are able to respond to novel antigens. This effect shortens the amount of time required to clear subsequent infections.
Between primary and secondary infections, or following vaccination
Vaccination
Vaccination is the administration of antigenic material to stimulate the immune system of an individual to develop adaptive immunity to a disease. Vaccines can prevent or ameliorate the effects of infection by many pathogens...
, a virus may undergo antigenic drift
Antigenic drift
The immune system recognizes viruses when antigens on the surfaces of virus particles bind to immune receptors that are specific for these antigens. This is similar to a lock recognizing a key. After an infection, the body produces many more of these virus-specific receptors, which prevent...
, in which the viral surface proteins (the epitopes) are altered through natural mutation, allowing the virus to escape the immune system. When this happens, the altered virus preferentially reactivates previously activated high-affinity memory B cells and spur antibody production. However, the antibodies produced by these B cells generally ineffectively bind to the altered epitopes. In addition, these antibodies inhibit the activation of lower-affinity naive B cells that would be able to make more effective antibodies to the second virus. This leads to a less effective immune response and recurrent infections may take longer to clear.
Original antigenic sin is of particular importance in the application of vaccines. The specificity and the quality of the immune response is often diminished in individuals who are repeatedly immunized (by vaccination or recurrent infections). However, the impact of antigenic sin on protection has not been well established, and appears to differ with each infectious agent vaccine, geographic location, and age.
.
In cytotoxic T cells
A similar phenomenon has been described in cytotoxic T cells (CTL). Several groups have attempted to design vaccineVaccine
A vaccine is a biological preparation that improves immunity to a particular disease. A vaccine typically contains an agent that resembles a disease-causing microorganism, and is often made from weakened or killed forms of the microbe or its toxins...
s for HIV and hepatitis C
Hepatitis C
Hepatitis C is an infectious disease primarily affecting the liver, caused by the hepatitis C virus . The infection is often asymptomatic, but chronic infection can lead to scarring of the liver and ultimately to cirrhosis, which is generally apparent after many years...
based on induction of cytotoxic (CTL) responses. The finding that CTL may be biased by original antigenic sin, may help to explain the limited effectiveness of these vaccines. Viruses like HIV are highly variable and undergo mutation frequently, and thus, due to original antigenic sin, HIV infection induced by viruses that express slightly different epitopes (than those in a viral vaccine) would fail to be controlled by the vaccine. In fact, the vaccine might make the infection even worse, by "trapping" the immune response into the first, ineffective, response it made against the virus.
See also
- Antibody-dependent enhancement
- Cell mediated immunity
- Humoral immunityHumoral immunityThe Humoral Immune Response is the aspect of immunity that is mediated by secreted antibodies produced in the cells of the B lymphocyte lineage . B Cells transform into plasma cells which secrete antibodies...
- Polyclonal response