Defects in lymphocyte immune tolerance checkpoints may lead to inappropriate recognition of platelet self-antigens, causing immune thrombocytopenia (ITP). In Evans syndrome, a central defect resulting in persistence of an autoreactive lymphocyte clone produces ITP and chronic thrombocytopenia. Alemtuzumab-associated ITP may be due to of a central defect in immune tolerance that develops during initial recovery of the lymphocyte pool and resolves as further reconstitution of B and T lymphocytes occurs, concurrent with improvement in the platelet count. In most cases of childhood ITP, an acquired loss of peripheral tolerance due to of immune stimulation by an exogenous precipitant (viral antigen, immunization) typically resolves once exposure to the antigen dissipates, leading to spontaneous remission of ITP. Conceptualized platelet count trends are representative of the potential for platelet count recovery after limited or no intervening medical therapy; because of inter-individual disease-modifying factors, remissions may not occur in every patient. Pink-shaded lymphocytes represent non self-reactive species; purple-shaded lymphocytes represent those with autoreactive potential. Professional illustration by Kenneth X. Probst.