T-Cell Mediated Immune Responses
T-cell activation
Upon activation by antigen, signals from the TCR and coreceptors alter the pattern of gene transcription for proliferation and differentiation into effector T cells (TH1, TH2, or CTL). The effector activity of the T cell is accomplished through the cytokines that the T cell produces (see below table). TCR binding to antigen and initial T-cell activation involves a cascade of signaling events that include the transcription factors NF kB, nuclear factor of activated T cells (NFAT), and activator protein 1 (AP-1). The production of IL-2 in response to T-cell activation is important for the initial proliferation and differentiation of the T cell. The immunosuppressive drugs cyclosporine A and tacrolimus (also called FK506) disrupt the signals from the TCR, thereby inhibiting the production of IL-2. Rapamycin inhibits the signaling from the IL-2 receptor.
T-cell effector functions
1. Nonviral intracellular parasites such as mycobacteria, Listeria, and certain protozoa are primarily eliminated by T-cell–macrophage immunity. Antigen-specific TH1 cell activation with the release of IFN-g and other macrophage-activating factors enhances effective immunity to these bacterial intracellular pathogens.
2. Viruses must be eliminated from both extracellular sites and infected cells.
- Antibodies neutralize virus particles in blood and tissue fluids to prevent further infection of host cells. These antibodies also serve as opsonins to assist with phagocytosis. Antibodies are generally ineffective against infected cells.
- CTL cells recognize infected cells via class I MHC presentation of viral peptides. The CTL then directly kills the infected cells in an antigen-specific manner and secretes lymphokines, such as IFN-g. Cytotoxic granule release (granulolysin, perforin, and granzymes) by the CTL is focused toward the infected cell, which is triggered to die by apoptosis; healthy, nearby cells are not affected. In addition, CTLs can induce apoptosis via FAS ligand binding to FAS on the target cells.
- NK cells kill infected (and tumor) cells in a non–antigen-specific manner by binding to MHC like molecules using a variety of receptors. NK cells kill their target cells using mechanisms similar to those used by CTLs.
- IFN-g (secreted by CTL, NK, and TH1 cells) and IFN-a and IFN-b (secreted by fibroblasts and other cells) provide additional antiviral immunity by binding to receptors on nearby uninfected cells to induce the synthesis of kinases and endonucleases (i.e., antiviral proteins), which inhibit viral and cellular growth. Interferons also upregulate MHC protein expression, which makes infected cells more visible to T cells.
3. Tumors are modified host cells and must be eliminated by the immune system, usually by cell-mediated immunity via CTL and NK cells.
4. Graft rejection.
T-cell memory
T-cell immune responses give rise to long-lived immunological memory (memory cells) and protective immunity.
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