Diagnosis: General Immunology
• Central tolerance is the mechanism by which T-cell and B-cell populations are culled to only non–self-reactive clones.
• T- and B-cell clones that recognize self-peptides/epitopes do arise, but they are eliminated in the thymus or bone marrow, respectively, before they can enter the periphery.
• Positive selection of nonreactive cells with functional T-cell receptors or B-cell receptors also takes place. Positive selection of self-cognate cells with regulatory function gives rise to “natural” T regulatory cell populations.
• According to some estimates, over 90% of the T cells generated in the thymus are never released into the periphery.
• Tissue-specific antigens are expressed in the thymus due to autoimmune regulator (AIRE) activation.
• A key concept of alloreactivity is that adaptive immune cells are educated to be tolerant to self-human leukocyte antigens (HLAs) during their development; however, their reactivity to foreign HLAs expressed by an allograft was never screened out.
