T-Lymphocyte

Aka: T-Lymphocyte, T-Cell, T-Cell Activation, T-Cell Surface Receptor, T-Helper Cell, Helper T-Cell, CD4+ Cell, T-Cytotoxic Cell, Cytotoxic T-Cell, CD8+ Cell

1. See Also
   1. White Blood Cell (Leukocyte)
   2. Lymphocyte
   3. Immune System
   4. B-Lymphocyte (B Cell)
   5. Natural Killer Cell (NK cell)
2. Definitions
   1. T-Lymphocytes (T-Cells)
      1. T-Cells are responsible Cell-Mediated Immunity
      2. T-Cells are named for where they mature and differentiate (Thymus)
      3. T-Cells target Intracellular Pathogens (e.g. viruses and Intracellular Bacteria) and cancer cells
         1. Humoral Immunity (antibodies) are in contrast unable to affect Intracellular Pathogens
3. Physiology
   1. T-Cells
      1. Derived in Bone Marrow
      2. Migrate to Thymus
         1. Maturation and Differentiation into two cell lines with different T-Cell Receptors (CD4 and CD8)
      3. Release into peripheral circulation
   2. T-Cell Surface Receptors and Accessory Molecules
      1. T-Cell Receptors (TCR)
         1. Bind the Antigen on the Antigen Presenting Cell (APC)
         2. Similar structure to Antibody
            1. Each chain (a, b, g or d) has a constant region (C) and a variable region (V)
            2. Variable region (V) on each chain forms Antigen binding site
         3. TCR Types (based on polypeptides ab or gd)
            1. TCR-alpha-beta (TCRab+)
            2. TCR gamma-delta (TCRgd+)
         4. Plasticity
            1. T-Cell Receptors (TCR) have variable regions whose genes may be rearranged
            2. Rearranging variable region genes allows for a reflex change in TCR binding target
               1. Similar mechanism to B-Cell Immunoglobulin Gene modification
      2. T-Cell Signal Transduction related Costimulatory Receptors (Allows for T-Cell Activation)
         1. CD3 and Zeta (Z) are part of T-Cell Receptor Complex (along with TCR)
            1. CD3 and Zeta (Z) are involved with signal transduction from T-Cell surface to inside of T-Cell
            2. T-Cell Receptors together with CD3 and Zeta (Z) are known as T-Cell Receptor Complex
            3. T-Cell Receptor Complex binds Peptide-MHC Complex as first signal in T-Cell Activation
         2. CD28
            1. Binds Ligand B7 (receptor found on APCs) as part of second signal in T-Cell Activation
      3. T-Cell Co-Receptors
         1. CD4 binds peptide/Antigen-MHC Class 2 complex on surface of Antigen Presenting Cells (APC)
         2. CD8 binds peptide/Antigen-MHC Class 1 complex on surface of Antigen Presenting Cells (APC)
      4. Adhesion Molecules (T Cell Surface Receptor Proteins that bind Ligands on Antigen Presenting Cell)
         1. Lymphocyte Function Associated Antigen-1 or LFA-1
            1. Binds Ligands intracellular Adhesion Molecule 1-3 (ICAM 1-3)
         2. Cluster of Differentiation 2 (CD2)
            1. Binds Ligand LFA-3
         3. Cluster of Differentiation 44 (CD44)
            1. Binds Ligand Hyaluronate
   3. Naive T-Cell Activation
      1. 
      2. T-Cell Receptor (TCR) binds to MHC-Antigen complex on Antigen Presenting Cells (APC)
      3. T-Cell Surface CD28 binds to B7 Ligand on Antigen Presenting Cell
      4. T-Cell Surface LFA-1 (Lymphocyte Function Associated Antigen) binds ICAM1 on Antigen Presenting Cells
      5. Interleukin-2 (IL2) produced by naive T Cells
         1. Stimulate T Cell proliferation
4. Types: T-Cells
   1. Effector Cells
      1. T-Helper Cells (CD4+ Cells)
         1. T-Helper Cell Proliferation and Activation is stimulated by Antigen Presenting Cells (see above)
            1. Binding to T-Cell Surface Receptors and Accessory Molecules AND
            2. Interleukin 1 or IL-1 (released from Antigen Presenting Cells)
               1. T-Helper Cells then develop Interleukin 2 (IL-2) receptors once activated
         2. Releases Interferon
            1. Stimulates Phagocytosis by Macrophages
            2. Activates Natural Killer Cells
            3. Suppresses viral replication
         3. Releases interleuken 2
            1. Promotes T-Cell proliferation (including Cytotoxic T Cells, and subsequently memory cells)
            2. Promotes B-Cell proliferation (memory cells and plasma cells) to generate antibodies
         4. Additional functions
            1. Aid Macrophages in destroying phagocytized Bacteria
            2. Contribute to Graft Rejection, responding to the graft's foreign MHC, activating T-Cytotoxic Cells
      2. T-Cytotoxic Cells (CD8+ Cells)
         1. Responds to cell surface MHC I combined with degraded peptide Antigens (foreign material marker)
            1. Specific cytotoxic T cells form for each Antigen (e.g. virus)
            2. Cytotoxic T-Cell Specificity is similar to Antibody and T-Helper Cell Specificity
         2. Cytotoxic T Cells Target and destroy cells marked as foreign
            1. Tumor cells
            2. Virus-infected cells
            3. Transplanted or grafted cells (Transplant Rejection)
      3. Memory Cells
         1. Cytotoxic T Cells proliferate and form Memory Cells, promoted by Helper T Cells
   2. Suppressor Cells
      1. T Suppressor Cells (Regulatory T Cells)
         1. Suppress immune cell activation
         2. Prevents autoimmune reactions by promoting self tolerance
   3. Other Cells
      1. Apoptosis of some cells not otherwise differentiated
5. References
   1. Guyton and Hall (2006) Medical Physiology, p. 419-50
   2. Mahmoudi (2014) Immunology Made Ridiculously Simple, MedMaster, Miami, FL