BIO444 T Cell Functions
T Cell Activation & Effector Functions
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Killer T Cell Engaging a Cancer Cell
Presentation by Alex Ritter with Dr. Bi-Chang Chen, Dr. Wesley Legant, & Dr. Liang Gao
Focus on T Cell Activation & Effector Functions
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Functions of T Cells in Host Defense
Activated immune cells are called effector cells.
Most effector T cells migrate to infection sites to eliminate microbes.
Some CD4+ effector cells remain in lymphoid organs to assist B lymphocytes in producing high-affinity antibodies.
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Effector T Cells
Activated T cells migrate to infected tissues via extravasation.
Changes in cell surface molecules facilitate travel to infection sites.
Integrins enable homing to inflamed tissue by binding to receptors on blood vessel endothelium.
Recruits effector T cells from the bloodstream.
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Cytotoxic T Cells
Three phases in cell-mediated cytotoxicity:
Binding to the target.
Rearrangement of cytoplasmic granules and release of contents.
Induction of target cell death.
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Cytotoxic CD8+ T Cells
CD8+ cytotoxic T lymphocytes (CTLs) kill infected cells.
After activation, CTLs synthesize cytotoxins packaged into lytic granules.
Granzymes (granule enzymes) are discharged upon encountering infected cells.
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Cytotoxin Release
CTLs kill infected cells through cytotoxin secretion.
Perforin creates pores in target cell membranes, delivering granzymes.
Granzymes initiate proteolytic cleavage, activating nucleases and degrading the nucleus.
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Target Cell Death
Target cells undergo apoptosis (programmed cell death).
Cells shrink and shed membrane-bound vesicles, which are taken up by macrophages.
CTLs detach, synthesize more lytic granules, and seek new targets.
One CTL can kill multiple infected cells.
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Three Subsets of CD4+ Helper T Cells
CD4+ helper T cells differentiate into:
Th1 (type 1 helper T cells)
Th2 (type 2 helper T cells)
Th17 (signature cytokine: IL-17)
Some activated CD4+ T cells produce mixed cytokines, complicating classification.
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Development of Th1 Cells
Differentiation driven by the types of microbes and cytokines produced by dendritic cells.
Cytokines guide the differentiation of antigen-activated T cells.
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Helper T Cells as Cytokine Factories
Functions of CD4+ T cell subsets depend on the cytokines they produce.
Key cytokines include TNF, IFN-γ, IL-4, IL-5, IL-6, IL-10, IL-17, and IL-21.
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Regulation and Function of T Helper Subtypes
Table summarizing polarizing cytokines, master gene regulators, effector cytokines, and functions of TH1, TH2, TH9, TH17, and Treg cells.
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Th2 Cells
Induced by parasitic worm infections.
Promote IgE production for mast cell and eosinophil-mediated destruction of parasites.
Signature cytokines: IL-4, IL-5, IL-13.
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Th17 Cells
Develop in response to extracellular bacterial and fungal infections.
Induce inflammatory reactions to destroy these organisms.
Major cytokines: IL-17, IL-21, IL-22.
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Regulatory CD4+ T Cells (Treg)
Important for immune suppression and self-tolerance.
Express inhibitors like CTLA-4 and PD-L1.
Limit activities of effector TH and CTLs.
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Th0 Cells
Unbiased T helper cells that can produce various cytokines.
Differentiation directed by cytokines at recruitment sites.
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B Cells as MHC Class II APCs
B cells use surface immunoglobulin as antigen receptors.
Continuously extract and present antigens via MHC class II molecules.
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Decline of the Immune Response
T cell survival and proliferation maintained by antigen and cytokines.
Post-infection, T cells die by apoptosis, leaving memory lymphocytes.
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Inhibitory Receptors
Negative costimulatory receptors (CTLA-4, PD-1) help turn off activation.
Critical for limiting and terminating immune responses.
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Memory Cells
A fraction of activated T lymphocytes become long-lived memory cells.
Ready to respond rapidly upon re-exposure to pathogens.
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Summary of Effector T Cells
Six types of effector T cells:
Cytotoxic CD8+ CTLs
Helper CD4+ cells: TH1, TH2, TH17, TFH, Treg
TH cells produce cytokines for pathogen elimination; CD8+ T cells induce apoptosis in infected or cancerous