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What altered T cell is used to treat adults with certain types of large B-cell lymphoma?
What altered T cell is used to treat adults with certain types of large B-cell lymphoma?
What role do dendritic cells play in the initiation of T-cell responses?
What role do dendritic cells play in the initiation of T-cell responses?
Which characteristic of dendritic cells makes them particularly effective at initiating primary T-cell responses?
Which characteristic of dendritic cells makes them particularly effective at initiating primary T-cell responses?
What is necessary for dendritic cells to activate naïve T-cells?
What is necessary for dendritic cells to activate naïve T-cells?
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How do dendritic cells respond to microbial infections?
How do dendritic cells respond to microbial infections?
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Where do dendritic cells preferentially migrate after capturing antigens?
Where do dendritic cells preferentially migrate after capturing antigens?
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Dendritic cells express receptors that enable them to capture microbes and respond to microbes
Dendritic cells express receptors that enable them to capture microbes and respond to microbes
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Dendritic cells carry antigens from _______ to _________ lymphoid organs to then present to naive T cells.
Dendritic cells carry antigens from _______ to _________ lymphoid organs to then present to naive T cells.
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What is the primary role of CD28:B7 interaction in T cell activation?
What is the primary role of CD28:B7 interaction in T cell activation?
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What is the first signal required for T cell activation?
What is the first signal required for T cell activation?
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Which T cell population is primarily activated by class II MHC molecules?
Which T cell population is primarily activated by class II MHC molecules?
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What process follows the antigen recognition by naïve T cells during activation?
What process follows the antigen recognition by naïve T cells during activation?
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Dendritic cells present peptides from protein antigens primarily to which type of T cell?
Dendritic cells present peptides from protein antigens primarily to which type of T cell?
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Which costimulatory interaction is essential for T cell activation after antigen recognition?
Which costimulatory interaction is essential for T cell activation after antigen recognition?
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The production of which molecule is crucial for promoting T cell survival, proliferation, and differentiation following activation?
The production of which molecule is crucial for promoting T cell survival, proliferation, and differentiation following activation?
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What is the role of the CD40L interaction in the T cell activation?
What is the role of the CD40L interaction in the T cell activation?
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Which of the following is necessary for a complete T cell response to occur?
Which of the following is necessary for a complete T cell response to occur?
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Which receptor interaction is primarily responsible for the initial activation of naive T cells?
Which receptor interaction is primarily responsible for the initial activation of naive T cells?
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What is a primary outcome of T lymphocyte activation?
What is a primary outcome of T lymphocyte activation?
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Which interaction serves to inhibit effector T cell activation in peripheral tissues?
Which interaction serves to inhibit effector T cell activation in peripheral tissues?
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Which interaction is critical for the development of helper T cells and subsequent antibody responses?
Which interaction is critical for the development of helper T cells and subsequent antibody responses?
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What is the effect of CTLA-4:B7 interaction on T cell activation?
What is the effect of CTLA-4:B7 interaction on T cell activation?
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Which condition is CTLA-4 specifically approved to treat?
Which condition is CTLA-4 specifically approved to treat?
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What is a therapeutic application currently being explored for inhibitors of the CD40L:CD40 pathway?
What is a therapeutic application currently being explored for inhibitors of the CD40L:CD40 pathway?
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Which of the following therapies is currently approved for tumor immunotherapy?
Which of the following therapies is currently approved for tumor immunotherapy?
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Which disease is CTLA-4 currently in clinical trials for treatment?
Which disease is CTLA-4 currently in clinical trials for treatment?
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What is the primary purpose of CTLA-4 in therapeutic use?
What is the primary purpose of CTLA-4 in therapeutic use?
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What are the 5 functional responses of T cell activation?
What are the 5 functional responses of T cell activation?
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What is the primary function of IL-2 in T cell biology?
What is the primary function of IL-2 in T cell biology?
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Which cell type is the main producer of IL-2 following antigen recognition?
Which cell type is the main producer of IL-2 following antigen recognition?
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How does IL-2 exert its effects in the immune response?
How does IL-2 exert its effects in the immune response?
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Which of the following cytokines is increased in production due to the action of IL-2?
Which of the following cytokines is increased in production due to the action of IL-2?
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In what manner does IL-2 impact T cell differentiation?
In what manner does IL-2 impact T cell differentiation?
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What does clonal expansion of T cells specifically increase?
What does clonal expansion of T cells specifically increase?
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Which statement accurately characterizes the daughter cells produced during clonal expansion of lymphocytes?
Which statement accurately characterizes the daughter cells produced during clonal expansion of lymphocytes?
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How is clonal expansion defined in the context of T cells?
How is clonal expansion defined in the context of T cells?
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Which aspect of clonal expansion ensures the effectiveness of T cell responses?
Which aspect of clonal expansion ensures the effectiveness of T cell responses?
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In clonal expansion, what is the significance of all progeny sharing the same antigen specificity?
In clonal expansion, what is the significance of all progeny sharing the same antigen specificity?
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Which type of T cell is primarily responsible for cytotoxic functions?
Which type of T cell is primarily responsible for cytotoxic functions?
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What is a key characteristic of memory T cells?
What is a key characteristic of memory T cells?
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How do effector T cells differentiate into memory cells?
How do effector T cells differentiate into memory cells?
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Which cytokines are typically secreted by CD4+ effector T cells?
Which cytokines are typically secreted by CD4+ effector T cells?
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Which of the following statements correctly describes T cell differentiation?
Which of the following statements correctly describes T cell differentiation?
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What are the two pathways memory cells can develop?
What are the two pathways memory cells can develop?
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Which of the following characteristics is NOT associated with memory T cells?
Which of the following characteristics is NOT associated with memory T cells?
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What role does IL-7 play in the context of memory T cells?
What role does IL-7 play in the context of memory T cells?
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Which statement about the number of memory T cells compared to naive T cells is accurate?
Which statement about the number of memory T cells compared to naive T cells is accurate?
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How do memory T cells respond to previously encountered antigens compared to naive T cells?
How do memory T cells respond to previously encountered antigens compared to naive T cells?
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Which factor contributes to the prolonged survival of memory T cells?
Which factor contributes to the prolonged survival of memory T cells?
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What is one of the primary factors that leads to the decline of T cell responses?
What is one of the primary factors that leads to the decline of T cell responses?
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Which mechanism is NOT responsible for the decline of T cell populations?
Which mechanism is NOT responsible for the decline of T cell populations?
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What role does BH3-only protein Bim play in the decline of T cell responses?
What role does BH3-only protein Bim play in the decline of T cell responses?
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Which statement accurately reflects the importance of T cell response decline in the immune system?
Which statement accurately reflects the importance of T cell response decline in the immune system?
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Which of the following processes does NOT contribute to T cell decline following antigen elimination?
Which of the following processes does NOT contribute to T cell decline following antigen elimination?
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Study Notes
T-cell Response Initiation
- T-cell responses begin in peripheral lymphoid organs.
- Protein antigens are transported to these organs after entering the body.
Dendritic Cell Role in T-cell Response
- Dendritic cells (DCs) capture protein antigens in tissues and epithelia.
- DCs transport these antigens to draining lymph nodes.
Properties of DCs for Effective T-cell Activation
- DCs are located in areas where microbes commonly enter the body.
- DCs express receptors that recognize and bind to microbes.
- DCs migrate to T-cell-rich zones in lymph nodes.
- Mature DCs express high levels of co-stimulatory molecules necessary for naïve T-cell activation.
- DCs can ingest infected cells and tumor cells, presenting antigens to CD8+ T cells.
T Cell Activation
- Naïve T cells, which circulate in secondary lymphoid organs, require activation to gain functionality.
- Antigen recognition by T cells triggers activation, leading to:
- Cytokine secretion: Cells release signaling molecules to communicate with other cells.
- Proliferation: Increases in the number of T cells with specific antigen recognition.
- Differentiation: Naïve T cells develop into effector or memory T cells.
Signals for T Cell Activation
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Signal 1: Antigen recognition is the primary activation signal for T cells:
- CD4+ and CD8+ T cells recognize peptide-MHC complexes on antigen-presenting cells (APCs).
- Multiple T cell surface proteins contribute to activation.
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Signal 2: Costimulation is a second signal required for T cell activation:
- Signal 2 works alongside antigen recognition (signal 1) to stimulate T cells.
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CD28:B7 interaction: A crucial costimulatory pathway, CD28 on T cells interacts with B7 molecules on APCs, promoting survival, proliferation, and differentiation of activated T cells.
Dendritic Cell Role in Activation
- Dendritic cells activate naïve T cells:
- They present peptides from endocytosed protein antigens in association with MHC class II molecules to CD4+ T cells.
- They present peptides from cytosolic and nuclear proteins displayed by MHC class I molecules to CD8+ T cells.
T Cell Activation & CD28 Family Receptors
- T cell activation is influenced by activating and inhibiting signals from the CD28 family receptors
-
Activating interactions:
- CD28:B7 (key for activating naive T cells)
- ICOS:ICOS-Ligand (critical for helper T cell development and antibody responses )
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Inhibitory interactions:
- CTLA-4:B7 (inhibits initial T cell activation in secondary lymphoid organs)
- PD:PD-Ligand (inhibits the activation of effector cells in peripheral tissues)
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Outcomes of T Cell Activation:
- Cytokine secretion
- T cell proliferation (increase in number of cells)
- Differentiation (naive T cells become effector or memory cells)
Therapeutic Costimulatory Blockade
- CTLA-4-Ig is an approved therapy for rheumatoid arthritis and transplant rejection.
- CTLA-4-Ig is currently in clinical trials for the treatment of psoriasis and Crohn’s disease.
- Inhibitors of the CD40L:CD40 pathway are also in clinical trials for transplant rejection and chronic inflammatory diseases.
- Antibodies against CTLA-4 and PD-1 are approved or are in clinical trials for the immunotherapy of tumors.
Therapeutic Costimulatory Blockade
- CTLA-4 is an approved therapy for rheumatoid arthritis and transplant rejection.
- CTLA-4 is currently in clinical trials for the treatment of psoriasis and Crohn’s disease.
Inhibitors of the CD40L:CD40 Pathway
- Inhibitors of the CD40L:CD40 pathway are also in clinical trials for transplant rejection and chronic inflammatory diseases.
Immunotherapy of Tumors
- Antibodies against CTLA-4 and PD-1 are approved or are in clinical trials for the immunotherapy of tumors.
IL-2 Secretion and IL-2Rα Expression
- IL-2 is a crucial cytokine that promotes T cell growth, survival, and differentiation.
- IL-2 is primarily produced by CD4+ T cells shortly after encountering an antigen and receiving co-stimulatory signals.
- IL-2 has an autocrine function, meaning it acts on the very cells that produce it, and a paracrine function, meaning it can influence neighboring cells.
- IL-2's key roles include:
- Stimulating T cell survival and proliferation.
- Promoting T cell differentiation into various subtypes.
- Enhancing the production of IFN-gamma and IL-4 by T cells.
- Playing a critical role in the survival of certain T cell populations.
Clonal Expansion of T Cells
- Proliferation of T cells results in an increase in the number of antigen-specific clones.
- Clonal expansion is the production of daughter cells from a single cell.
- In clonal expansion of lymphocytes, all progeny cells (daughter cells) share the same antigen specificity.
Activated T Cell Differentiation
- CD4+ T cells differentiate into effector cells that express specific surface molecules and secrete cytokines.
- CD8+ T cells differentiate into cytotoxic T cells.
Memory Cell Development
- Memory cells develop for specific antigens and can persist for years or a lifetime.
- Memory cell development can occur via a linear pathway from effector cells or from divergent differentiation of effector populations.
Properties of Memory T Cells
- Memory T cells express higher levels of anti-apoptotic proteins, allowing them to survive for longer periods.
- They respond quicker to known antigens compared to naive T cells.
- The body maintains a larger pool of memory cells specific to a particular antigen than naive T cells for the same antigen.
- Memory T cells can migrate to peripheral tissues, enabling them to respond to infection at various sites.
- In the absence of antigens, memory T cells undergo slow proliferation, which contributes to their long-term persistence.
- The maintenance of memory T cells relies on the cytokine interleukin-7 (IL-7).
Memory T Cells - Properties
- Increased anti-apoptotic protein expression - leads to enhanced survival, allowing for long-term immune memory.
- Faster response to antigens - allows for quicker and more efficient immune response upon re-exposure to the same pathogen.
- Higher abundance - compared to naive T cells specific for the same antigen.
- Migration to peripheral tissues - facilitates rapid immune response at the site of infection.
- Slow proliferation - in the absence of antigen, ensuring the long-term maintenance of the memory cell pool.
- IL-7 dependence - for survival and maintenance of memory T cell population.
T Cell Response Decline
- T cell response contraction is necessary for maintaining immune homeostasis.
- The decline is triggered by the elimination of the antigen.
- Cessation of co-stimulation and growth factor production (IL-2) contributes to the decline.
- Activation of cellular stress sensors, specifically the BH3-only protein Bim, initiates apoptosis in T cells during contraction.
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Description
Activation of T Lymphocytes