- 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)||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),
|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.