tolerance and autoimmunity

• clonal selection theory

  clones of lymphocytes can recognise any antigen. lymphocytes that react to self are deleted. lymphocytes that interact with an antigen with high affinity are activated and undergo clonal expansion
• clonal deletion

  elimination of lymphocytes that bind to self antigens, this is the main mechanism of central tolerance
• self tolerance

  tolerance to self antigens
• autoimmunity

  breakdown in tolerance to self antigens
• peripheral tolerance

  anergy, ignorance, cell death, supression
• B cell no reactivity to self

  maturation and migration to periphery
• b cell interaction with multivalent self

  deletion or receptor editing
• b cell interaction with self molecule

  anergy
• b cell interaction with low affinity self

  ignorant
• mature B cells will express IgD and IgM, immature will only express IgM
• peripheral tolerance

  anergy, deletion, regulated by inhibitory receptors
• t cell selection occurs in the cortex and medulla
• t cell positive selection

  cTEC expresses MHC 1 and 2, there is selection of cells with moderate avidity for self MHC, interaction of TCR with MHC class 1 gives rise to CD8 T cell, and interaction of TCR with MHC class 2 gives rise to CD4T. if there is weak or no binding, there is death by ignorance
• negative T cell selection

  high avidity interaction with self MHC: deletion or Treg generation. mature self restricted, self tolerant, single positive cells will leave thymus and enter circulation
• anergy

  lack of co-stimulation. self reactive cells are inactivated and cannot respond to antigen
• ignorance

  antigen is sequestered and not exposed to self reactive t cells, or is present at very low concentration
• lupus

  abnormalities in T, B, and complement responses. inflammation, tissue damage, and pain
• myasthenia gravis

  antibodies bind, internalise, and degrade acetylcholine, muscles don't respond to acetylcholine, no sodium influx, no muscle contraction