a large number of chemicals induce or exacerbate autoimmune - like diseases in man . because of the complexity of processes involved , these adverse effects are often if not always missed in standard toxicity testing . to date 
 no validated and generally applicable predictive animal model exists and only a few chemicals have actually been shown to induce adverse autoimmune effects in certain animals . 
 the popliteal lymph node assay ( plna ) is a very promising animal test to ( pre)screen for systemic immunosensitizing , including autoimmunogenic potential . 
 this review describes the essentials of the various plnas against the background of current understanding of chemically induced systemic immunostimulation . 
 the most simple primary plna measures enlargement of the popliteal lymph node 6 - 8 days after subcutaneous injection of a chemical into the footpad . 
 the primary plna can distinguish between immunostimulating ( both sensitizers and irritants ) and innocent chemicals but does not assess the involvement of t cells or immunosensitization . 
 for this , but also for elucidation of relevant mechanisms , detection of anamnestic responses in secondary plnas or responses to reporter antigens in the modified plna are suitable . to date over 100 compounds ( drugs and environmental pollutants ) have been tested , and results show a good correlation with reported immunostimulating ( both autoimmunogenic and allergic ) potential . 
 importantly , no false - negative chemicals were detected if metabolism was considered . 
 the various types of the plna , but in particular the secondary and modified plnas , await extensive validation before they can be recommended as a standard test for autoimmunogenic potential.imagesfigure 2figure 3