When a potentially harmful substance, such as a virus or bacterium, enters the body, cells in the immune system produce antibodies. Antibodies are proteins which attach to specific harmful invaders, or antigens, neutralizing them and preventing infection. The next time a specific threat enters the body, the immune system remembers it and antibodies are produced much more rapidly to deal with it. In the case of some diseases which recur, such as dengue fever, antibodies attach to the dengue virus but fail to neutralize it. Instead, they actually make the virus more able to enter cells and infect them, and this is known as antibody-dependent enhancement.
Antibody-dependent enhancement can make diseases worse, because it enables viruses to attach themselves to cells and cause infection. In addition to its association with dengue fever, antibody-dependent enhancement is also thought to occur in HIV infection and influenza. Although none of these diseases can be cured, many people recover from dengue fever and influenza without treatment, and drugs can prolong life for those with HIV.
In the case of dengue fever, several different forms of the virus exist. Normally, during a first infection with dengue, patients experience either no symptoms or only minor symptoms. When infection occurs again, with another form of dengue, more severe symptoms occur. These can include high fever, skin rashes, headache and vomiting. This is a reversal of what usually happens with immunity, when a second episode of infection is recognized and dealt with much more quickly and effectively.
Antibody-dependent enhancement occurs because antibodies are produced which attach to one part of the dengue virus. This section is the same in all the different virus forms, so the antibodies can attach to all of them. Other, varying parts of the virus are responsible for infection, so the antibodies are not able to neutralize all the different forms. When a new form of dengue virus enters the body, an antibody attaches to it but the virus remains intact.
As the antibody is attached to the virus, the body does not mount any further immune response and the virus goes unchallenged. This is sometimes referred to as original antigenic sin, because the body retains its first response to the antigen, as if it has been indelibly marked. As well as allowing a virus to remain under the immune system's radar, antibody-dependent enhancement enables it to enter cells and infect them. This is because the antibody attached to the virus can bind to cell receptors. The virus can then enter cells it would not be able to attach to on its own.