T cells (T lymphocytes) are the main cells of cell-mediated immunity and directly eliminate virus-infected cells, cancer cells, and transplanted tissues. T cells mature in the thymus through strict selection and are educated to recognize self-MHC while not attacking the body’s own tissues.
Basic Knowledge
Maturation and selection in the thymus: T-cell precursor cells move from the bone marrow to the thymus and undergo two stages of selection: positive selection (allowing T cells that can recognize self-MHC to survive) and negative selection (eliminating T cells that react strongly with self-antigens = clonal deletion). This establishes central immune tolerance.
T-cell subsets: Helper T cells (CD4⁺): Recognize MHC class II molecules on APCs. After activation, they produce interleukins (IL-2, IL-4, IFN-γ, etc.) and help B cells and Tc cells. They differentiate into subsets such as Th1 (promotes cell-mediated immunity), Th2 (promotes humoral immunity), and Th17 (inflammation). Cytotoxic T cells (CD8⁺/CTL): Recognize MHC class I molecules on APCs. They contact infected cells and release perforin and granzymes to induce apoptosis. Regulatory T cells (Treg/CD4⁺CD25⁺): Suppress immune responses and prevent autoimmunity.
Process of cell-mediated immunity: ① Dendritic cells present antigens → ② helper T cells are activated (produce IL-2 and proliferate) → ③ CTLs and Th1 cells proliferate → ④ CTLs contact virus-infected cells → ⑤ perforin/granzymes induce apoptosis → ⑥ memory T cells form.
Explain how cytotoxic T cells identify virus-infected cells, including the roles of MHC class I molecules and perforin.
Answer: A virus-infected cell presents fragments of viral proteins (antigenic peptides) on MHC class I molecules. A CTL (CD8⁺ T cell) recognizes this complex with its T-cell receptor, attaches closely to the infected cell, and releases perforin. Perforin forms pores in the membrane of the infected cell, after which granzymes enter and induce apoptosis (programmed cell death), eliminating the infected cell.
- Positive selection = allows T cells capable of recognizing self-MHC to survive
- Negative selection = eliminates T cells that react strongly with self-antigens
- CD4⁺ helper T cells = recognize MHC class II; command the response
- CD8⁺ CTLs = recognize MHC class I; kill infected cells
- Perforin = forms pores in membranes; granzymes = induce apoptosis
- Treg = suppresses immune responses and prevents autoimmune disease
- IL-2 = interleukin that promotes T-cell proliferation
Points to Note
① CTLs do not “kill” cells directly; they “induce” apoptosis (programmed cell death). ② HIV infects and destroys CD4⁺ T cells (helper T cells), causing both humoral and cell-mediated immunity to become dysfunctional. ③ Cancer immunotherapy (immune checkpoint inhibitors) is a strategy that removes the brakes on CTLs and strengthens their attack on cancer cells.
Practice
- Explain the significance of positive and negative selection in the thymus.
- Which class of MHC molecule is recognized by CD4⁺ T cells and CD8⁺ T cells, respectively?
- Explain how perforin and granzymes work together to eliminate infected cells.