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Immune Regulation: Tregs, γδ T Cells, and Fc Receptor Binding in B Cells

Explore the mechanisms of immune regulation through the roles of regulatory T cells, γδ T cells, and Fc receptor binding in B cells. Learn about early response mechanisms, antigen concentration, and immunological memory.

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Immune Regulation: Tregs, γδ T Cells, and Fc Receptor Binding in B Cells

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  1. Topics • Immune regulation •  T cells • Fc receptor binding in B cells • Early response mechanisms • Antigen concentration • Immunological memory MICR 415 / 515 / 682

  2. Immune regulation MICR 415 / 515 / 682

  3. Idiotypic network Variable regions of Ab are able to serve as antigens that elicit the production of anti-idiotipic Ab by the same individual i. e. Modulation of the immune response in Schistosomiasis MICR 415 / 515 / 682

  4. Regulatory T cells • The immune system has to: • Protect the host from pathogens • Distinguish between self and non-self structures • Distinguish harmful from innocuous Ag to prevent non-essential responses • Induction of Ag-specific self tolerance MICR 415 / 515 / 682

  5. Tregs = CD4+ regulatory T cells • CD4+ CD25+ (IL-2 R  chain) • Naturally occurring • Cell-cell contact (molecules not yet defined) • Depletion leads to autoimmune diseases • 5 – 10 % of all peripheral CD4+ T cells • Anergic (hyporesponsive) • Suppress activation of CD25- T cells • Inhibit IL-2 transcription • Th3 and Type 1 T regulatory (Tr1) • Contact independent • IL-10, TGF-β • Altered state of development (not an independent cell lineage) MICR 415 / 515 / 682

  6.  T cells • TCR composed of   chains • 2 sets • Found in lymphoid tissues of all vertebrates • Display some diversity of TCR • Intra-epithelial in some vertebrates • Limited diversity of TCR • Limited recirculation • Recognize ligands expressed by infected cells • Heat shock proteins, MHC IB molecules • Direct and rapid response to the precence of infected cells MICR 415 / 515 / 682

  7.  T cell as regulators of IR • Mice deficient on  T cells mount exaggerated responses to foreign and to self Ag. MICR 415 / 515 / 682

  8. Fc receptor binding in B cells • Engagement of Fc receptors in B cells reduces the B activation and reduces production of antibodies MICR 415 / 515 / 682

  9. Early response mechanisms • Th0 differentiate into Th1 and Th2 and determines if the response is cellular or humoral • Cytokines present at the site of proliferation MICR 415 / 515 / 682

  10. Th1 induction • IL-12, IFN- • Produced by dendritic cells, macrophages, NK cells in response to viral infection and invasion by some intracellular bacteria MICR 415 / 515 / 682

  11. Th2 induction • IL-4 and IL-6 • Produced by NK1.1 CD4 T cell • Invariant TCR • Do not require TCR:MHC interaction of recognition • Recognize some MHC IB molecules MICR 415 / 515 / 682

  12. MICR 415 / 515 / 682

  13. + - + - Th 2 Th 1 • IL-4 • IL-5 • IL-10 • IL-2 • IFN- Immunoregulation Th0 MICR 415 / 515 / 682

  14. Antigen concentration • High amounts of Ag -> Th1 • Low amounts of antigen -> Th2 • Strong MHC-peptide to TCR interaction ->Th1 • Weak MHC-Peptide to TCR interaction -> Th2 • High affinity of peptide to MHC ->Th1 • Low affinity of peptide to MHC ->Th2 MICR 415 / 515 / 682

  15. Antigen concentration MICR 415 / 515 / 682

  16. Immunological memory • Effective responses eliminate pathogen or Ag from the system • Removal of most effector cells as part of the restoration of tissue integrity • Cells die via apoptosis and are cleared by macrophages • Cells that survive become memory cells. • T cells survive almost indefinitely. MICR 415 / 515 / 682

  17. MICR 415 / 515 / 682

  18. Immunological memory • B cells develop primary focy of proliferation 5 days after inoculation of Ag • Initial Ab production Early response Trapping of Ag FDC presentation (iccosomes) MICR 415 / 515 / 682

  19. Differentiation, germinal center formation • Somatic hypermutation, selection • Exponential proliferation for 2 or 3 days (6 or 7 cell division cycles) • 90% Differentiation into plasma cells (2 – 3 day life span, then apoptosis) • 10% life longer, fate is unknown MICR 415 / 515 / 682

  20. Germinal centers last for 3 – 4 weeks • Some B cells continue to proliferate for months • Migrate to the mucosas • Differentiate into plasma cells • Last for years MICR 415 / 515 / 682

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