T-Cells

  • Differentiation of T cells
  • Positive selection
    • Thymic cortex.
    • T cells expressing alpha-beta TCRs capable of binding self-antigen + MHC on cortical epithelial cells survive.
  • Negative selection
    • Thymic medulla.
    • T cells expressing TCRs with overly high affinity for self-antigens in the thymic medullary epithelial and dendritic cells undergo apoptosis (via Fas-FasL pathway) or become regulatory T cells.
    • Tissue-restricted self-antigens are expressed in the thymus due to the action of autoimmune regulator (AIRE); deficiency leads to autoimmune polyendocrine syndrome-1.
  • T cell subsets
   Th1 cell Th17 cell Treg Th2 cell
SECRETES IL-2 (T-cell growth activator and CD8+ T cell activator)

IFN-γ

TNFα

IL-17, IL-21, IL-22 TGF-ß, IL-10, IL-35 IL-4 (class switching to IgG & IgE),

IL-5 (eosinophil chemotaxis and activation, maturation of B cells to plasma cells, and class switching to IgA),

IL-6 (fever, acute phase reactants),

IL-10 (inhibits Th1 phenotype),

IL-13

FUNCTION Activates macrophages and cytotoxic T cells to kill phagocytosed microbes, mediates delayed-type hypersensitivity Immunity against extracellular microbes, through induction of neutrophilic inflammation Prevent autoimmunity by maintaining tolerance to self-antigens Activate eosinophils and promote production of IgE for parasite defense
INDUCED BY IFN-γ, IL-12 TGF-β, IL-1, IL-6 TGF-β, IL-2 IL-2, IL-4
INHIBITED BY IL-4, IL-10 (from Th2 cell) IFN-γ, IL-4  IL-6 IFN-γ (from Th1 cell)
IMMUNODEFICIENCY Mendelian susceptibility to mycobacterial disease Hyper-IgE syndrome IPEX  
  • Macrophage-lymphocyte interaction
    • Th1 cells secrete IFN-γ, which enhances the ability of monocytes and macrophages to kill microbes they ingest. This function is also enhanced by interaction of T cell CD40L with CD40 on macrophages.
  • Cytotoxic T cells
    • Kill virus-infected, neoplastic, and donor graft cells by inducing apoptosis.
    • Release cytotoxic granules containing preformed proteins (eg, perforin punctures, granzyme B activates caspase).
    • Cytotoxic T cells have CD8, which binds to MHC I on virus-infected cells.
    • Expression of FasL, binds Fas on target cell activating apoptosis
  • Regulatory T cells
    • Help maintain specific immune tolerance by suppressing CD4 and CD8 T-cell effector functions.
    • Identified by expression of CD3, CD4, CD25, and FOXP3.
    • Activated regulatory T cells (Tregs) produce anti-inflammatory cytokines (eg, IL-10, TGF-β).
    • IPEX (Immune dysregulation, Polyendocrinopathy, Enteropathy, X-linked) syndrome— genetic deficiency of FOXP3 → autoimmunity. Characterized by enteropathy, endocrinopathy, nail dystrophy, dermatitis, and/or other autoimmune dermatologic conditions. Associated with diabetes in male infants.

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