Adaptive Immunology

• The adaptive immune system is specific or acquired
• The adaptive immune system is slow to develop
• The adaptive immune system can augment and amplify the immune response
• The adaptive immune system can confer long-lasting protection from infection
• The adaptive immune system involves the recognition of non-self antigens in the presence of self
• Cells of the adaptive immune system are derived from a lymphoid progenitor cell
• The innate immune system happens immediately but is short-lived
• The adaptive immune system takes longer to activate but is much longer lasting
• T cell development

  • pre-T cell
  • selection of T cells with appropriately rearranged receptors for antigen
  • naive T cells
  • encounter with antigen-bearing DC leads to activation and functional polarisation to effector or memory T cell
  • carry out effector functions
• T cell tolerance

  • t cells that cannot bind to self MHC undergo apoptosis (positive selection)
  • t cells interact with DCs. recognise peptide - MHC complexes with medium or high affinity undergo apoptosis (negative selection)
  • weak affinity to peptide and MHC I become CD8 cells (cytotoxic T cells)
  • weak affinity to peptide and MHC II become CD4 cells (helper T cells)
• During the tolerance selection process, hundreds of T cells will die.
• Tolerance prevents T cells and B cells from attacking self tissue
• Peripheral tolerance

  T-cells that recognize self-antigens are inactivated or deleted in peripheral tissues.
• Central tolerance

  T-cells that recognize self-antigens are eliminated during development in the thymus.
• Central T cell tolerance mechanisms

  • deletion
  • anergy
  • indifference/ignorance
• Peripheral T cell tolerance mechanisms

  • indifference/ignorance
  • anergy
  • regulatory cells
  • deletion
• Even after T cell selection and tolerance, cells with potential for autoreactivity remain available
• Antigen presenting cells

  • dendritic cells
  • macrophages
  • B cells
• When dendritic cells interact with naive T cell two signals need to occur:

  • t cell receptor binds to antigen presenting receptor, recognising pathogen as being non-self and needing to be activated
  • B7 protein on dendritic cell (CD80 and CD86) bind to CD28 on naive CD4 cell
• activated CD4 release IL-2 which binds to other CD4 and amplifies cytokine production
• CD4 subsets

  • Th1
  • Th2
  • Th17
  • Treg
• IL-12 activates Th1
• IL-4 activates Th2
• IL-1B and IL-6 activate Th17
• TGF-B and IL-10 activate Treg
• Th1 releases IFN-y, IL-2, TNF-a
• Th2 release IL-4, 5 and 13
• Th17 releases IL-17
• Treg releases TGF-B and IL-10
• Th1 cells - defence against intracellular bacteria and viruses, cell mediated response
• IFN-y released by Th1 activates B cell to become plasma cell and release opsonising antibodies and activates macrophages to display Fc receptor y1 which binds to Ig2a
• IFN-y and IL-2 released by Th1 activate NK cells to increase cytotoxic cytokine secretion and activate CD8 cells to increase cytoxicity and cytokine secretion, and increase their survival
• Th2 cells - defence against extracellular bacteria and parasites, humoral mediated response
• IL-4 released by Th2 activates naive B cells to become plasma cells and release IgE
• IL-4 and IL-13 released by Th2 activate macrophages to increase cytokine secretion, eosinophil and basophilic recruitment, healing and suppression of inflammation.
• IL-2 and IL-5 released by Th2 activate eosinophils for recruitment and survival
• IL-3 and IL-9 released by Th2 activate basophils and mast cells for recruitment and survival
• Th17 cells - defence against some bacteria and fungi
• Th17 cells

  • pro-inflammatory response
  • chronic inflammation
  • autoimmune disease
• Th17 cells can be beneficial in helping increase the amount of phagocytes present in tissue