T- and B-Cell Activation

  • T-cells may have another classification based on “experience”
    • Naïve – never experienced an infection
    • Effector – actively responding to a stimulus
    • Memory – previously experienced an infection
  • APCs: B cells, dendritic cells, Langerhans cells, macrophages.
    • Dendritic cells take up antigen by endocytosis, constitutively express MHC Class II and costimulatory B7 molecule. Able to activate all forms of T cells (naïve, effector, memory)
    • B lymphocytes take up antigen by receptor-mediated (membrane-bound) antibody endocytosis and constitutively express MHC Class II. Can stimulate all T cells.
    • Macrophages are phagocytes that only inducably express MHC Class II and B7 and can only activate effector and memory T cells, not naïve T cells. MHC class II protein complex is encoded by the human leukocyte antigen gene complex (HLA).
      •  Bare lymphocyte syndrome is an immunodeficiency resulting from a defect in expression of HLA class II antigens on the surfaces of antigen presenting cells.
  • Two signals are required for T-cell activation, B-cell activation, and class switching.
  • T-cell activation
    1. Dendritic cell (specialized APC) samples antigen, processes antigen, and migrates to the draining lymph node.
    2. T-cell activation (signal 1):
      • Antigen is presented on MHC II of APC and recognized by TCR on T-helper (CD4+) cell.
      • Endogenous or cross-presented antigen is presented on MHC I of nucleated cells to T-cytotoxic (CD8+) cell.
    3. Proliferation and survival (signal 2):
      • Costimulatory signal via interaction of B7 protein (CD80/86) on dendritic cell/macrophage and CD28 on naïve Th1 cell.
      • IL-2 from CD4+ Th1 cell provides (helps) second activation signal to CD8+ T-cell
    4. Th cell activates and produces cytokines. Tc cell activates and is able to recognize and kill virus-infected cell.
  • B-cell activation and class switching
    1. Antigen binding by surface IgM or IgD → B-cells become plasma cells and secrete immunoglobulins OR
    2. Antigen presentation by Th cells
      1. Th-cell activation as above.
      2. B-cell receptor–mediated endocytosis; foreign antigen is presented on MHC II of B cell is recognized by TCR on Th cell.
      3. CD40 receptor on B cell binds CD40 ligand (CD40L) on Th cell. (Mutated in
      4. Th cell secretes cytokines that determine Ig class switching of B cell. IL-4 and IL5 mediate B-cell isotype switching, hypermutation and maturation to plasma cells
      5. B cell activates and undergoes class switching, affinity maturation in germinal centers of lymph nodes, and antibody production.

 

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