Podcast
Questions and Answers
What distinguishes central tolerance from peripheral tolerance in lymphocyte development?
What distinguishes central tolerance from peripheral tolerance in lymphocyte development?
- Central tolerance involves receptor editing, whereas peripheral tolerance relies solely on clonal deletion.
- Central tolerance occurs in primary lymphoid organs, while peripheral tolerance occurs in secondary lymphoid tissues. (correct)
- Central tolerance is specific to B cells, while peripheral tolerance is specific to T cells.
- Central tolerance utilizes positive selection, while peripheral tolerance uses negative selection.
If a developing B cell, during negative selection in the bone marrow, strongly binds to a soluble self-antigen, what is the most likely outcome for this B cell?
If a developing B cell, during negative selection in the bone marrow, strongly binds to a soluble self-antigen, what is the most likely outcome for this B cell?
- It upregulates IgM expression and becomes anergic.
- It is rescued by editing of light chain genes and continues maturation.
- It undergoes apoptosis and clonal deletion.
- It upregulates IgD expression and becomes anergic with a short lifespan. (correct)
Which of the following mechanisms is NOT a component of central tolerance in T cells?
Which of the following mechanisms is NOT a component of central tolerance in T cells?
- Clonal deletion, where autoreactive T cells are physically removed.
- Clonal diversion, where T cells differentiate into regulatory T cells.
- Clonal ignorance, where T cells ignore antigens hidden from lymphocyte circulation. (correct)
- Clonal inactivation, where T cells are rendered unable to respond to self-antigens.
A developing thymocyte expresses a T cell receptor (TCR) that weakly binds to self-MHC molecules on cortical epithelial cells. What is the most likely outcome for this thymocyte?
A developing thymocyte expresses a T cell receptor (TCR) that weakly binds to self-MHC molecules on cortical epithelial cells. What is the most likely outcome for this thymocyte?
What is the functional role of RAG1 and RAG2 proteins during T cell development in the thymus?
What is the functional role of RAG1 and RAG2 proteins during T cell development in the thymus?
Which process is most crucial for ensuring that developing T cells are restricted to recognizing antigens presented by self-MHC molecules?
Which process is most crucial for ensuring that developing T cells are restricted to recognizing antigens presented by self-MHC molecules?
A mature T cell in the periphery encounters a self-antigen that is normally sequestered behind the blood-brain barrier. What mechanism of peripheral tolerance is most likely to prevent an autoimmune response?
A mature T cell in the periphery encounters a self-antigen that is normally sequestered behind the blood-brain barrier. What mechanism of peripheral tolerance is most likely to prevent an autoimmune response?
How does receptor editing contribute to B cell tolerance?
How does receptor editing contribute to B cell tolerance?
In the context of T cell tolerance, what is the role of regulatory T cells (Tregs)?
In the context of T cell tolerance, what is the role of regulatory T cells (Tregs)?
A researcher discovers a novel mutation that impairs the presentation of peripheral tissue antigens in the thymus. What is the most likely consequence of this mutation?
A researcher discovers a novel mutation that impairs the presentation of peripheral tissue antigens in the thymus. What is the most likely consequence of this mutation?
Flashcards
Thymocyte Migration & Selection
Thymocyte Migration & Selection
Immature T cells migrate from the bone marrow to the thymus, where they undergo selection based on their T cell receptors (TCRs) and surface molecules like CD4 and CD8.
Positive Selection
Positive Selection
The process by which thymocytes that can recognize self-MHC molecules receive signals that allow them to survive.
Negative Selection
Negative Selection
The elimination of T cells that strongly recognize self-antigens, preventing autoimmunity. Occurs in the thymus.
T Cell Tolerance
T Cell Tolerance
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B Cell Selection
B Cell Selection
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B Cell Positive Selection
B Cell Positive Selection
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B Cell Negative Selection
B Cell Negative Selection
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B cell receptor editing
B cell receptor editing
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Immunological Tolerance
Immunological Tolerance
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Central Tolerance Mechanisms
Central Tolerance Mechanisms
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Study Notes
- Thymocytes migrate from the bone marrow to develop T cell receptors (TCRs) and CD4/CD8 surface molecules.
- T cell selection and tolerance processes, including positive and negative selection, shape mature T cells.
- 98% of thymocytes undergo apoptosis within the thymus due to failure of positive selection.
- T cell selection ensures MHC restriction and validation of a dominant circulating T cell population.
Positive Selection
- Occurs in the thymic cortical region.
- Immature thymocytes interact with cortical epithelial cells, which are also antigen-presenting cells (APCs).
- Thymocytes that fail to recognize self-MHC undergo apoptosis.
- RAG1, RAG2, and TDT proteins are upregulated to rearrange TCR alpha genes.
- Multiple alpha/beta TCR chain combinations increase the chances of passing positive selection.
- Cells with an alpha/beta TCR that recognizes self-MHC are then tested by negative selection.
Negative Selection & T Cell Tolerance
- Ensures self-tolerance in T cells.
- Central tolerance occurs in the thymus.
- Peripheral tolerance occurs in secondary lymphoid tissues.
- Central tolerance uses negative selection and receptor editing; T regulatory cells (T regs) are also selected.
- Mature T cells in the periphery expressing high affinity for self-antigen are suppressed or eliminated via apoptosis.
B Cell Selection
- B cells, like T cells, undergo positive and negative selection to eliminate autoreactive cells.
- Cortical epithelial interaction is vital for the presentation of antigen and selection of non-self-reactive B cells.
- Positive selection in B cells occurs when the pre-B cell receptor binds to an antigen. If binding doesn't occur, the cell dies. Peripheral positive selection can occur upon BCR-antigen interaction.
- Negative selection occurs when B cells strongly bind to self-antigens.
- Binding to self-antigen in the bone marrow results in apoptosis and clonal deletion.
- Binding to soluble self-antigen leads to IgD expression and low IgM, promoting anergy and short lifespan.
- Self-reactive B cells can be rescued via editing of light chain genes.
- Some B cells undergo somatic recombination for non-self-specific heavy and light chain combinations.
B Cell Tolerance
- B cell tolerance, like T cell tolerance, ensures lymphocytes aren't highly reactive to self-antigens.
- Tolerance can occur centrally or peripherally.
- Receptor editing significantly influences B cell tolerance.
Central vs Peripheral Tolerance
- Central Tolerance: Occurs in primary lymphoid organs. Antigens include those expressed in the thymus/bone marrow, those expressed in all cells, and those expressed in cells trafficking through the thymus/bone marrow
- Clonal deletion: Physical removal of the T/B cell.
- Clonal inactivation: The T/B cell is present but unable to respond.
- Clonal diversion: The T cell becomes a regulatory cell.
- Peripheral Tolerance: Occurs after cells emerge from the thymus and can see potential self-antigens in various tissues.
- The first three mechanisms are the same as central tolerance: deletion, inactivation, and diversion.
- Clonal ignorance: T cells escape because the antigen they recognize is hidden from lymphocyte circulation (e.g., antigens in the brain, eye, or testis).
- Help Deprivation: B cell and cytotoxic T cell responses need help from CD4+ helper cells.
- Suppression: Regulatory cells keep effector T cells in check.
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