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Questions and Answers
What is the primary function of the immunological synapse?
Which co-stimulatory molecule is specifically associated with CD4+ T cells?
What signals are necessary for T cell activation?
What role do ITAMs play in T cell signaling?
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How do CD4+ T cells and CD8+ T cells differ in their maturation and activation?
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Which cytokine is essential for the proliferation and differentiation of activated naive T cells?
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What happens to CD8+ T cells if they are missing CD28 during activation?
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Which of the following statements about memory T cells is true?
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What is the main purpose of the immunological synapse?
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Which two signals are essential for the activation of naive T cells?
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What are immunoreceptor tyrosine-based activation motifs (ITAMs)?
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What triggers tolerance/anergy in T cells?
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Which structure within the immunological synapse is primarily associated with receptor signaling?
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How do CD4+ and CD8+ T cells differ in their activation processes?
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What role do co-stimulatory signals play in T cell activation?
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What happens when both the first signal and second signal are delivered along with cytokines?
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What is the primary determinant of whether a thymocyte matures into a CD4+ or CD8+ T cell?
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How do T cells with high-affinity T-cell receptors (TCRs) for self-MHC/peptide complexes typically respond during negative selection?
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Which process allows T cells to leave the thymus and enter peripheral circulation after maturation?
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What role do ITAMs play in T cell signaling?
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What triggers the process of anergy in T cells?
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Which of the following statements correctly compares CD4+ and CD8+ T cell activation?
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What is the primary function of the immunological synapse?
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What best describes the 'homing' mechanism of T cells to secondary lymphoid tissues?
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Study Notes
Naive T cell activation
- After negative selection, T cells are mature and leave the thymus
- Both CD4+ and CD8+ T cells require a "first" and "second" signal for activation
- The "first" signal comes from TCR/CD4 and p:MHC class II complex on dendritic cell
- The "second" signal comes from CD28 co-stimulatory receptor & B7 (CD80/86)
- *CD40 & CD40L are key co-stimulatory molecules for CD4+ cells
- *4-1BB & 4-1BBL are key co-stimulatory molecules for CD8+ cells
- CD58 can also stimulate CD8+ T cells if CD28 is missing
- The first signal alone leads to tolerance/anergy
- First + second signal = Activation
- First + second signal + cytokines = Effector function
- If only the first signal is received, the T cell becomes tolerant, or anergic, and cannot be activated.
- The immunological synapse forms between a naive T cell and a dendritic cell
- It includes a central (c-SMAC) and peripheral (p-SMAC) supramolecular activation complex (c-SMAC)
- The c-SMAC mainly contains signaling molecules and the p-SMAC mainly contains adhesion molecules
Signal transduction
- The TCR and CD4 co-receptor bind to the p:MHC class II complex on the dendritic cell, delivering the first signal for T cell activation
- The CD28 co-stimulatory receptor on the T cell binds to the B7 (CD80/86) co-stimulator on the dendritic cell, delivering the second signal for T cell activation
- ITAMs (immunoreceptor tyrosine-based activation motifs) are conserved sequence that are repeated twice in the cytoplasmic tails of the TCR.
- They initiate intracellular immune signaling and activation of immune cells
- IL-2 is a cytokine that drives proliferation and differentiation of activated naive T cells
CD4+ and CD8+ T cell Maturation and Activation
- Both CD4+ and CD8+ T cells mature in the thymus and become single positive during positive selection
- CD4+ cells mature and differentiate into various subsets based on their role with different cytokine production
- The most important subtypes are TH1, TH2, TH17, Treg and Tfh
- CD8+ cells differentiate into cytotoxic T lymphocytes (CTLs)
- Their activation and differentiation depend on antigen presentation and cytokine signaling
- CD8+ cells are able to kill infected cells that present viral or tumor antigens
Immunological synapse
- It is an ordered structure that functions as an immunological synapse
- The immunological synapse is formed when two immune system cells bind with receptors and adhesion molecules
- It allows the exchange of signals and the secretion of effector molecules
Homing & Trafficking
- Homing refers to the process of T cells migrating from the thymus to secondary lymphoid tissues
- Lymphocyte trafficking is the movement of lymphocytes between different tissues
- They are regulated by chemokines, adhesion molecules and homing receptors that are expressed on the surfaces of lymphocytes
- T cells use chemokines to find their way to lymph nodes where they can encounter antigens.
- chemokines are specific for different lymphoid organs, providing precise guidance for homing.
Dendritic cell maturation and antigen presentation
- Dendritic cells act as antigen-presenting cells (APCs)
- They capture antigens and present them to T cells
- Maturation is a process that increases their ability to present antigens
- It involves changes in expression of MHC molecules, co-stimulatory molecules, and chemokine receptors
- During maturation, dendritic cells migrate from the tissues to the lymph nodes, where they can activate T cells
Memory T cells
- They are long-lived T cells that can rapidly respond to a re-exposure to a specific antigen
- They are generated from activated naive T cells during an immune response
- They provide long-term protection against pathogens
Importance and Significance of IL-2
- Interleukin-2 (IL-2) is a crucial cytokine that regulates T cell proliferation, differentiation, and survival
- It is mainly secreted by T cells (CD4+ and CD8+)
- It has different functions depending on the context and the stage of T cell activation
- IL-2 promotes the expansion of antigen-specific T cells
- It contributes to the establishment of memory T cells
- It also contributes to the suppression of immune responses
Central tolerance
- Ensures that T cells do not attack self-antigens or other antigens in the body
- It is established during thymic T cell development
- It is mainly mediated by negative selection
- It prevents the development of autoimmune diseases
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Description
This quiz covers the intricate process of naive T cell activation, focusing on the critical signals required for their activation, including the roles of TCR/CD4, MHC class II, and various co-stimulatory molecules. Understand the significance of the immunological synapse and how the first and second signals influence T cell behavior. Test your knowledge on the activation pathways essential for T cell function in the immune response.
