Towards a unified theory of immunity: dendritic cells, stress proteins and antigen capture.
In less than a decade, the archetypal view that the immune system exists primarily to distinguish "self" from "non-self" has been replaced by the paradigm that the immune system functions primarily to distinguish dangerous from non-dangerous antigens. This change is in part due to the recent reassertion of the importance of so-called innate immunity, which consists of non-specific components of the immune system such as macrophages that are active prior to exposure to antigens (In contrast, so-called acquired immunity depends upon the generation of B and T lymphocytes that are produced after exposure to the antigens and are specific for the antigens). The paradigm shift is also due to the recent proposal of the "danger model" of the immune system, which provides a conceptual mechanism by which the immune system might distinguish dangerous from non-dangerous antigens. The role of dendritic cells (DCs) in activating T lymphocytes is key to both innate immunity and the danger model. The purpose of this commentary is to add an additional piece to the emerging picture of immune-system function by suggesting that heat-shock, or stress, proteins play a central role in the activation of T lymphocytes by DCs. The uptake of stress proteins--whose expression is induced by monokines in the earliest phases of the innate immune response--by DCs might constitute a "danger" signal. However, through such a mechanism, DCs may capture antigens bound to stress proteins and improve their ability to present the antigens to other components of the immune system, such as cytotoxic T-cells. Invoking stress proteins to amplify the immune response in this manner can explain how animals can mount an effective primary immune response to an antigen despite having few T lymphocytes specific for that antigen. Finally, the "affinity-maturation" of antibody following a primary immune response would enable the much more efficient, specific antigen-capture by high affinity antibodies in a secondary immune response, resulting in a rapid and specific response or "memory" on re-exposure to the pathogen.
Quadrant Healthcare, Cambridge, UK.
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Colaco
D000818:Animals; D000941:Antigens / Q000502:physiology*; D003713:Dendritic Cells / Q000276:immunology*; D006360:Heat-Shock Proteins / Q000276:immunology*; D006801:Humans; D007109:Immunity / Q000502:physiology*; D018448:Models, Immunological
D000941:Antigens; D006360:Heat-Shock Proteins