Immunological memory

• Describe the longevity of immunological memory

  Immunological memory is very long lived and is ready to respond to a specific antigen. Example smallpox:

  • Can detect T cell responses up to 75 years after initial vaccination
  • Ability to produce anti-smallpox antibodies remains very high throughout life
• How does the memory cell pool stay constant?

  Balance between memory cell proliferation and death. Individual memory cells are not very long lived and only a small percentage of cells proliferate, which is due to production of cytokines by memory cells or other immune cells.
• How is immunological memory established?

  Immunological memory is established when the immune system encounters a pathogen for the first time and some immune cells develop a "memory" of the invader.This memory is long-lived and allows the body to respond more quickly and effectively if it encounters the same pathogen again.
• What are memory B cells?

  • Generated in germinal centres
  • Found in secondary lymphoid organs, but also in the circulation
  • Identified by the expression of the cell surface marker CD27
  • Express high affinity IgG, IgA, and IgE on their cell surface
  • Produce more antibody of higher affinity in the secondary response
• How does antibody production change in quantity following repeat infection?

  Memory B cells have higher expression of: surface immunoglobulins (BCR), MHC II, and co-stimulatory molecules (CD80/86). This increases ability to initiate interaction with helper T cells and can occur at lower doses of antigen, i.e., earlier on in infection. Therefore, there is an immediate production of IgG during secondary response.
• How does antibody production change in quality with repeat infections?

  Cells expressing higher affinity antibody are selected and expand, therefore permitting them to dominate in the secondary response. Further selection and expansion of high affinity antibody producing cells in subsequent responses.
• Describe how plasma cells contribute to immunological memory

  Plasma cells can be long-lived and reside within the bone marrow. They can constitutively make antibody to contribute to immunological memory. In order to form these long-lived plasma cells in the germinal centre they must express the transcription factor BLIMP-1 and they undergo proliferation, antibody class switching and affinity maturation. BCMA is required for survival of these cells.
• Describe the reactivation of memory cells

  Memory cells have already undergone class switch and affinity maturation. Re-exposure to antigen triggers memory cells to either:

  • begin expressing BLIMP-1, which causes them to become plasma cells
  • or proliferate to form more memory B cells
• What are the differences between B and T cells?

  • No class switch in T cells
  • This means memory T cells are harder to identify than memory B cells
  • No affinity maturation in T cells
• How are memory T cells made?

  Some activated T cells become long-lived memory cells, which require IL-7 and IL-15 for their survival. Memory T cells need contact with MHC peptide complexes to continue to proliferate.
• Describe memory T cell markers

  IL-7 receptor alpha is a good marker for activated T cells that will become memory cells. This is expressed by naive T cells and down regulated by most activated cells, but a small population of IL-7 receptor alpha positive cells are shown to be important memory cells.
• What are central memory cells?

  • CCR7 expression means cells home to T cell areas of peripheral lymphoid organs
  • more prone to TCR activation after antigen binding, making them more likely to be reactivated but are not activated as quickly as effector memory T cells
  • increase CD40 ligand quickly after antigen recognition
  • can relocalise rapidly to region where viral infection first enters lymph node
• What are effector memory T cells?

  • Don’t express CCR7, so do not home to lymph nodes
  • Instead express receptors that promote entry into peripheral non-lymphoid tissue, e.g., CCR3, CCR5, beta1 and beta2 integrins
  • Very rapidly produce cytokines when they recognise antigen
  • These cells can re-circulate through the blood and lymph system
• Describe the function of effector and central memory T cells

  Effector:

  • Quick initial response during secondary infection
  • BUT short life span and low proliferation

  Central:

  • Take longer to activate but provide more long-lived memory response
  • BUT after antigen stimulation become more like effector memory cells to help drive the secondary response

  There is a cross-over between the different types.
• What are tissue-resident memory T cells?

  These are a new subset of memory T cells that are similar to effector memory T cells but do not re-circulate and instead residue in tissues, such as the skin; therefore, they are involved in psoriasis.
• Describe how CD4+ T cells contribute to the development of CD8+ T cell memory

  In the absence of CD4+ T cells, there is insufficient development of CD8+ T cell memory. This is believed to be due to expression of CD40L and production of IL-2 by CD4+ T cells, which activate IL-7 receptor alpha to trigger development of memory CD8+ T cells. CD4+ T cells are also important for the maintenance of CD8+ memory T cells.