Overview
This lecture explains the activation and functions of CD4 T helper cells in cell-mediated immunity, detailing their differentiation pathways and their role in orchestrating immune responses.
Types of Lymphocytes and T Cells
- Lymphocytes include B cells and T cells, which are key to adaptive immunity.
- T helper cells express CD4; cytotoxic T cells express CD8.
- Helper T cells support other immune cells, while cytotoxic T cells kill infected or cancerous cells.
Activation of CD4 T Cells
- Naive T cells need two signals to activate: antigen presentation via MHC and costimulation (CD28 on T cell binds B7 on APC).
- The 'immune synapse' includes the T cell receptor, CD4, CD28, and their binding partners on APCs.
- Cytokines present during activation influence T helper cell differentiation.
Role of IL-2 and Clonal Expansion
- Activated T helper cells produce IL-2 and upregulate the high-affinity IL-2 alpha receptor.
- IL-2 binding drives T cell proliferation (clonal expansion) through autocrine stimulation.
Differentiation of T Helper Cell Subtypes
Th1 Cells
- Macrophages and dendritic cells infected with intracellular pathogens produce IL-12, and NK cells release interferon-gamma.
- These cytokines activate transcription factors (Stat1, Stat4, T-bet) causing differentiation into Th1 cells.
- Th1 cells secrete interferon-gamma and IL-2, enhancing macrophage killing and stimulating NK, CD8+ T, and B cells.
- Excessive Th1 responses may contribute to autoimmunity.
Th2 Cells
- Parasitic infections activate eosinophils, basophils, and mast cells, which release toxic granules.
- Antigen-presenting cells with parasite antigens produce IL-4, IL-5, and IL-10, leading to Th2 differentiation via Stat6 and Gata-3.
- Th2 cells produce IL-4, IL-5, IL-10, and IL-13, stimulating B cells to make IgE and activating granulocytes to fight parasites.
Key Terms & Definitions
- Naive T cell — T cell that has not yet encountered its specific antigen.
- Antigen Presenting Cell (APC) — Cell (like macrophage or dendritic cell) that displays antigen with MHC to activate T cells.
- Immune synapse — Contact site between a T cell and an APC where activation signals occur.
- Cytokines — Signaling proteins (e.g., IL-2, IL-12, interferons) that regulate immune responses.
- Clonal Expansion — Rapid multiplication of activated T cells.
Action Items / Next Steps
- Review cytokines involved in Th1 and Th2 differentiation.
- Study the roles of IL-2 and interferon-gamma in immune activation.
- Read textbook sections on cell-mediated immunity and T cell activation.