How CD4 T cells are activated
• DCs capture and process antigen from peripheral sites. They migrate to lymph nodes displaying the processed antigenic peptide in context with MHC.
• Naïve T cells continually recirculate through blood, spleen, lymph nodes, and MALT in search of DCs displaying a complementary MHC-peptide complex that can engage its TCR.
• If the naïve T cell TCR binds the MHC class II-peptide complex on the APC without engaging any costimulatory molecules, it becomes anergic (unresponsive) or undergoes apoptosis. However, if a naïve T cell TCR binds the MHC class II-peptide complex on the APC and the T cell is activated, then the T cell expresses CD40L which binds to CD40 on the APC. This induces expression of CD80/CD86 on the APC which binds to CD28 on the T cell, triggering production of IL-2 which binds to the IL-2R on the T cell, causing a positive feedback loop, and resulting in T-cell proliferation.
• Naïve T cells are activated to become one of the four distinct subpopulations of CD4+ T cells based on the cytokines produced by APCs in response to the antigen they are processing. The type of CD4+ T cell can be identified based on the cytokines it secretes.
• Th1 responses promote the production of opsonizing antibodies (IgG1) and induction of cellular cytotoxicity and macrophage activation. Important against pathogens that replicate intracellularly (virus, intracellular bacteria).
• Th2 responses promote IgE and IgG4 production and stimulate eosinophil development. Important for helminth infections.
• Th17 responses are important for defense against chronic infections with extracellular bacteria and fungi.
• Tregs are important for the establishment and maintenance of tolerance and suppression of immune response.
The activated T cell proliferates and its progeny travel throughout the body until they reach where the antigen has invaded. They are restimulated by local APCs and release their cytokines that contribute to augmenting the immune response by activating monocytes/macrophages.
Some activated T cells undergo further interactions with B cells in the lymphoid tissue, inducing a humoral immune response.
• Some activated T cells become long-lived memory T cells. Memory T cells are activated more easily and rapidly in a secondary immune response.