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 exis ts primarily to distinguish ''self' from ''non-self'' has been replace d by the paradigm that the immune system functions primarily to distin guish dangerous from non-dangerous antigens. This change is in part du e to the recent reassertion of the importance of so-called innate immu nity, which consists of non-specific components of the immune system s uch as macrophages that are active prior to exposure to antigens (In c ontrast, 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 p rovides a conceptual mechanism by which the immune system might distin guish dangerous from non-dangerous antigens. The role of dendritic cel ls (DCs) in activating T lymphocytes is key to both innate immunity an d the danger model. The purpose of this commentary is to add an additi onal piece to the emerging picture of immune-system function by sugges ting that heat-shock, or stress, proteins play a central role in the a ctivation of T lymphocytes by DCs. The uptake of stress proteins -whos e expression is induced by monokines in the earliest phases of the inn ate immune response- by DCs might constitute a ''danger'' signal. Howe ver, through such a mechanism, DCs may capture antigens bound to stres s proteins and improve their ability to present the antigens to other components of the immune system, such as cytotoxic T-cells. Invoking s tress proteins to amplify the immune response in this manner can expla in how animals can mount an effective primary immune response to an an tigen despite having few T lymphocytes specific for that antigen. Fina lly, the ''affinity-maturation'' of antibody following a primary immun e response would enable the much more efficient, specific antigen-capt ure by high affinity antibodies in a secondary immune response, result ing in a rapid and specific response or ''memory'' on re-exposure to t he pathogen.