Immunological self–nonself discrimination capacity is acquired during lymphopoiesis, formation of mature lymphocytes in the primary lymph organs and during immunopoiesis, the immune responses in the peripheral lymph organs. It rests on specific antigen recognition by B- and T cells, but, the innate immune defence system ensures antigen presentation and the delivery, or not, of associated co-stimulatory signals leading to immune responses or tolerance. Thus both, the acquired and the innate immune defences, play determinant roles in the immunological discrimination. Whether caused by infection or by other factors, alterations of lymphocytes or of antigen presentation can perturb self-tolerance and trigger autoimmune reactions.

Key Concepts:

• Self–nonself discrimination rests on both the natural and specific immune defences.
  
• During lymphopoiesis, recognition of antigen by immature B- or T cells leads to clonal deletion.
  
• During immunopoiesis, the development of immune responses or of tolerance largely depends on the cells’ environment leading or not to co-stimulatory signals.
  
• Lymphocytes ensure specific recognition; accessory cells detect internal or external danger signals, emit co-stimulatory signals and control lymphocyte activation or death.