T Cell Development and Activation PDF

CD4 T Cell Commitment Th1, Th2, Th17 40 Signaling Through Cytokine Receptors JAK:STAT Pathway 41  CD4 T Cell Fate Determined in Lymph Node Effector Cells Return to Site of Infection APCs tell T ce...

CD4 T Cell Commitment Th1, Th2, Th17 40 Signaling Through Cytokine Receptors JAK:STAT Pathway 41  CD4 T Cell Fate Determined in Lymph Node Effector Cells Return to Site of Infection APCs tell T cells which lineage they should commit to in order to deal with that pathogen (what cytokine profile is optimal for clearance of the specific pathogen). This ability to change phenotypes allows mature T cells that are specific for a pathogen to be flexible in the effect they will induce on an infected cell, thus allowing the host to deal with viruses, bacteria, 42 and even self antigens in different ways. Cytokine Milieu Determines CD4 T Cell Fate Th1, Th2, or Th17 43 Polarizing Immunity Toward a Specific Pathogen 44  Polarizing Immunity Toward a Specific Pathogen The Th1:Th2 Paradigm Cytokines produced during Th1 responses block the development of a Th2 response and vice versa. Presence of a specific pathogen polarizes the immune response toward either Th1 (viruses and intracellular bacteria) or Th2 (extracellular pathogens). 45 Classical and Alternative Macrophage Activation 46  Destruction of an Intracellular Pathogen APC Induces Th1 Immunity A macrophage (APC) infected with an intracellular bacteria expresses bacterial peptides bound to MHC-II on its surface and produces the cytokine IL-12. This IL-12 induces a Th1 response. The Th1 cell expresses CD40 ligand on its surface and, in response to the IL-12 from the macrophage, produces IFN-γ, which tells the macrophage to kill the bacteria living inside its vesicles. Together, the CD40:CD40L and IFN-γ interaction with the IFN-γ receptor tell the APC to kill the pathogen 47 residing inside. Granuloma Formation Tuberculosis Mycobacteria have evolved to survive within macrophages by resisting the killing activity of Th1 cells. This leads to formation of a multi-nucleated giant cell made up of multiple fused macrophages that contain mycobacteria. Granulomas are defined by the presence of these multi-nucleated giant cells surrounded by T cells, many of which are CD4. 48 Multiple Effects of Activated Th1 Cells on The Host 49  Production of Antibodies Contribution of Th2 Cytokines Activated Th2 cells also express CD40 ligand on their surface, and produce cytokines like IL-4, IL-5, and IL-6 that are involved in the induction of certain antibody isotypes. Please note that the Th1 cytokine IFN-γ can stimulate isotype switching of antigen-specific B cells toward IgG1 antibodies that can fix complement and interact with Fc receptors to enhance opsonophagocytosis. 50  Production of Antibodies Hapten:Carrier Systems and Conjugate Vaccines Polysaccharides cannot be presented to T cells, and immunity toward them is generated in a T cell-independent manner. To enhance immunity to polysaccharides, conjugate vaccines were created by linking polysaccharides to a protein (tetanus toxoid). The polysaccharide and protein are broken down within the endosome, but only the peptides are presented by the MHC. This leads to an interaction with a TCR that recognizes tetanus toxoid peptide bound to MHC, and that T cell becomes activated and tells the B cell to make antibody. The antibody produced is directed toward the polysaccharide that the B cell specifically recognizes. The B cell is specific for the polysaccharide, while the T cell is specific for tetanus toxoid. 51