Podcast
Questions and Answers
What is the primary location of T-cell development?
What is the primary location of T-cell development?
Thymic atrophy leads to an increase in thymic output as individuals age.
Thymic atrophy leads to an increase in thymic output as individuals age.
False
What are the two regions of the thymus?
What are the two regions of the thymus?
Cortex and Medulla
Hematopoietic stem cells migrate to the thymus from the ______.
Hematopoietic stem cells migrate to the thymus from the ______.
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Match the following cytokines and receptors with their roles in T-cell development:
Match the following cytokines and receptors with their roles in T-cell development:
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Which of the following is NOT a role of thymic epithelial cells?
Which of the following is NOT a role of thymic epithelial cells?
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Negative selection in the thymus ensures that only T cells that do not react against self-antigens are allowed to mature.
Negative selection in the thymus ensures that only T cells that do not react against self-antigens are allowed to mature.
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What phenomenon occurs in the thymus leading to a reduction in lymphocyte numbers after thymectomy in neonatal mice?
What phenomenon occurs in the thymus leading to a reduction in lymphocyte numbers after thymectomy in neonatal mice?
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What functional role does the c-Kit receptor play in thymocyte development?
What functional role does the c-Kit receptor play in thymocyte development?
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Negative selection occurs in the thymic cortex.
Negative selection occurs in the thymic cortex.
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What characterizes the Single-Positive (SP) stage in T-cell development?
What characterizes the Single-Positive (SP) stage in T-cell development?
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The _____ transcription factor controls the expression of self-antigens in medullary thymic epithelial cells.
The _____ transcription factor controls the expression of self-antigens in medullary thymic epithelial cells.
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What is one of the key processes during the transition from Double-Positive to Single-Positive stage?
What is one of the key processes during the transition from Double-Positive to Single-Positive stage?
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Promiscuous gene expression refers to the ability of medullary thymic epithelial cells to express a limited range of self-antigens.
Promiscuous gene expression refers to the ability of medullary thymic epithelial cells to express a limited range of self-antigens.
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What is the consequence of high-affinity TCR-MHC interactions during negative selection?
What is the consequence of high-affinity TCR-MHC interactions during negative selection?
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Mutations in the Aire gene can lead to _____ diseases.
Mutations in the Aire gene can lead to _____ diseases.
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What signals are primarily involved in the proliferation of Double-Negative cells?
What signals are primarily involved in the proliferation of Double-Negative cells?
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Study Notes
T-Cell Development Overview
- T cells are critical for adaptive immunity, recognizing pathogens and maintaining self-tolerance.
- T-cell development occurs in the thymus, a primary lymphoid organ.
- T-cell development takes 2-3 weeks, starting with HSCs from bone marrow migrating to the thymus.
- Thymus structure: Cortex (early development) and Medulla (late development & self-tolerance).
- Thymic output declines with age due to atrophy, but T cell competency persists.
Stages of T-Cell Development
- T-cell development progresses through distinct phases:
- Double-Negative (DN): CD4-CD8- (immature).
- Double-Positive (DP): CD4+CD8+ (express both markers).
- Single-Positive (SP): CD4+ or CD8+ (mature).
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DN Stage to DP Stage:
- Notch signaling: Dictates T-cell lineage commitment.
- IL-7 receptor: Crucial for thymocyte survival.
- c-Kit receptor: Promotes proliferation via interaction with SCF (stem cell factor).
- TCR β-chain rearrangement: Leads to a pre-TCR complex, halting further β-chain rearrangement.
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DP Stage to SP Stage:
- Positive selection (cortex): Ensures T cells recognize self-MHC molecules with low affinity. Choosing either CD4 or CD8 pathway.
- Negative selection (medulla): Eliminates autoreactive T cells binding self-antigens with high affinity.
Mechanisms Ensuring Immune Tolerance
- Aire expression: mTECs (medullary thymic epithelial cells) express a variety of self-antigens. Critical for negative selection.
- Mutation in Aire causes autoimmune diseases like APECED.
- Affinity model: Low affinity TCR-MHC interactions trigger positive selection; high affinity triggers negative selection.
- Avidity model: Focuses on the number of engaged TCRs; higher engagement leads to negative selection.
Key Cytokines and Receptors
- IL-7: Supports thymocyte survival and early development.
- IL-15: Important for regulating mature T-cell homeostasis, especially memory T-cells.
- c-Kit receptor: Promotes early thymocyte proliferation through interaction with SCF.
Conclusion
- Thymus is crucial for T-cell development and immune self-tolerance.
- Crucial microenvironment provided by thymus stromal cells for guiding development and selection.
- IL-7, IL-15, and c-Kit receptors are vital for thymocyte survival and differentiation.
- Mature T cells leave the thymus to populate peripheral tissues.
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Description
Explore the intricate process of T-cell development, which is vital for adaptive immunity. This quiz covers the stages from immature T-cells in the thymus to their maturation and key molecular signals involved. Understand the roles of different T-cell stages and how age affects T-cell competency.