For reasons that are usually unknown, self-tolerance mechanisms sometimes fail, causing T or B cells (or both) to react against the animal’s own molecules.
Figure 24–21 Mechanisms of immunological self-tolerance. When a self-reactive immature B cell binds its self molecule in the central lymphoid organ where the cell is produced, it may alter its antigen receptor so that it is no longer self-reactive (cell 1); this process is called receptor editing. Alternatively, when either an immature B or T cell binds its self molecule in a central lymphoid organ, it may die by apoptosis, a process called clonal deletion (cell 2). Because these two forms of tolerance (shown on the left) occur in central lymphoid organs, they are called central tolerance.
When a self-reactive naïve B or T cell escapes tolerance in the central lymphoid organ and binds its self molecule in a peripheral lymphoid organ (cell 4), or in another peripheral tissue, it will generally not be activated, because the binding usually occurs in the absence of sufficient co-stimulatory signals; instead, the cell may die by apoptosis (often after a period of proliferation), be inactivated, or be suppressed by a regulatory T cell. These forms of tolerance (shown on the right) are called peripheral tolerance. As discussed later, the cells providing the co-stimulatory signals are  T lymphocytes for B cells and usually dendritic cells for T cells (not shown). For T cells at least, both activation and tolerance in a peripheral lymphoid organ usually occurs on the surface of a dendritic cell, although the dendritic cells are different in the two cases.
Myasthenia gravis is an example of such an autoimmune disease. Most of the affected individuals make antibodies against the acetylcholine receptors on their own skeletal muscle cells; these receptors are required for the muscle to contract normally in response to nerve stimulation, which releases acetylcholine (see Figure 11–39). The antibodies interfere with the normal functioning of the receptors so that the patients become weak and may die because they cannot breathe. Similarly, in juvenile (type 1) diabetes, adaptive immune reactions against insulin-secreting β cells in the pancreas kill these cells, leading to severe insulin deficiency.
Innate immune responses triggered by pathogens at sites of infection help activate adaptive immune responses in peripheral lymphoid organs. The adaptive immune system is composed of many millions of B and T cell clones, with the cells in each clone sharing a unique cell‑surface receptor that enables them to bind a particular pathogen antigen. The binding of antigen to these receptors, with the help of co‑stimulatory signals, stimulates the lymphocyte to proliferate and differentiate into an effector cell that can help eliminate the pathogen. Effector B cells secrete antibodies, which can act over long distances to help eliminate extracellular pathogens and their toxins. Effector T cells, by contrast, produce cell‑surface and secreted co‑stimulatory molecules, which mainly act locally to help other immune cells eliminate the pathogen; in addition, some T cells can induce infected host cells to kill themselves.