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Questions and Answers
Where do T-cells primarily mature?
Which cells in the thymus play a crucial role in guiding T-cell development?
What process allows T-cells to recognize antigens presented via HLA?
What happens to T-cells with TCRs that bind self-antigens with high affinity?
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Which of the following is NOT a characteristic of the thymus?
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In T-cell development, where do lymphoid progenitors divide under the influence of IL-7?
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What is the main characteristic that differentiates T-cell development from B-cell development in terms of maturation location?
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Where are double negative 3 (DN3) cells mostly found during T-cell development in the thymus?
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What happens if a developing T-cell in the thymus has a useless beta chain of the TCR?
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What is the phenotype of a developing T-cell immediately after both TCR chains have been recombined?
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What happens if a DP (double positive) cell in the thymus interacts with thymic epithelial cells expressing self-antigens with very low affinity?
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What is the consequence when DP cells interact with thymic epithelial cells expressing self-antigens with high affinity?
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What is the fate of DN cells that do not rearrange their beta chain correctly in the thymus?
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What happens to a DP T-cell with 'low-medium' affinity for a thymic epithelial cell's HLA bound to self antigen during positive selection?
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What happens to a DP T-cell with 'high' affinity for a thymic epithelial cell's HLA bound to self antigen during negative selection?
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What happens to some T-cells that recognize self during negative selection?
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What determines whether a DP cell expresses CD4 or CD8 co-receptor after surviving positive and negative selection?
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During positive selection, what leads to a DP T-cell being allowed to survive?
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What provides the driving force for lymph to enter lymph capillaries?
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Which duct drains the right arm, thoracic region, and right head/neck into the blood system?
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What happens to external pressure when lymph enters lymph capillaries?
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What is the role of trunks in the lymphatic system?
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During T-cell development, beta chain of the TCR is shuffled before the alpha chain
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95% of T-cells do not survive positive and negative selection
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Choice of CD8 or CD4 receptors occurs in the cortex of the thymus
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Where does central tolerance occur?
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What are the consequences of defects in AIRE gene?
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Which of the following is the major polarizing cytokine for T-reg cells?
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What happens when CD28 of Th cell binds to B7 (CD80/86) of CD4+ T-reg cells?
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CTLA-4 is expressed on Th cells. Which ligand of the T-reg cell does it bind to with high affinity?
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Which of the following receptors is expressed on T-reg cells in high levels?
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Which of the following antibodies plays a role in maintaining barrier integrity against microbial invasion?
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Which of the following diseases is associated with deficiencies in both the IL-2R-alpha gene and the CTLA-4 gene?
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Which of the following is true regarding the spleen?
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Which of the following signals do B-cells need to be activated without the help of Th cells?
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Where does the thoracic duct drain into?
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Study Notes
T-Cell Maturation and Development
- T-cells primarily mature in the thymus.
- Thymic epithelial cells play a crucial role in guiding T-cell development.
- T-cells recognize antigens through a process that involves the interaction with Human Leukocyte Antigen (HLA).
Affinity and Selection
- T-cells with TCRs that bind self-antigens with high affinity typically undergo apoptosis (negative selection).
- Characteristics of the thymus include its role in T-cell development, while a lack of lymphatic drainage is NOT a characteristic.
- Lymphoid progenitors divide under the influence of IL-7 in the thymus.
Differences in T-Cell and B-Cell Development
- T-cell maturation occurs in the thymus, whereas B-cells mature in the bone marrow.
Development Stages in Thymus
- Double negative 3 (DN3) cells are found in the thymus during T-cell development, particularly in the subcapsular zone.
- Developing T-cells with a useless beta chain of the TCR typically fail to progress in development.
- After TCR chain recombination, a developing T-cell is termed a double positive (DP) T-cell.
Positive and Negative Selection Outcomes
- DP cells interacting with self-antigens at low affinity survive positive selection.
- High affinity interactions result in apoptosis during negative selection.
- DN cells not correctly rearranging their beta chain will be eliminated.
Co-Receptor Expression and Selection Processes
- The expression of CD4 or CD8 co-receptors in a DP cell is determined by the type of TCR and selection outcome.
- DP T-cells survive positive selection through weak interactions with thymic epithelial cells.
Lymphatic System
- The driving force for lymph entry into capillaries is the pressure gradient.
- The right lymphatic duct drains lymph from the right arm, thoracic region, and right head/neck into the bloodstream.
- When lymph enters capillaries, external pressure decreases.
Functions of Lymphatic Trunks
- Trunks in the lymphatic system serve as major conduits for draining lymph and transporting immune cells.
Central Tolerance and AIRE Gene
- Central tolerance, where self-reactive T-cells are eliminated, occurs in the thymus.
- Defects in the AIRE gene lead to autoimmunity due to impaired negative selection.
T-Cell Regulation and Signaling
- The major polarizing cytokine for T-reg cells is IL-2.
- Binding of CD28 on Th cells to B7 (CD80/86) on T-reg cells enhances regulation.
- CTLA-4 binds to CD80/86 with high affinity on T-reg cells.
Immune Response and Antibody Function
- T-reg cells express high levels of CD25.
- Antibodies such as IgA contribute to maintaining barrier integrity against pathogens.
- Combined deficiencies in IL-2R-alpha and CTLA-4 genes can lead to severe immune dysfunction.
Spleen and B-Cell Activation
- The spleen plays a key role in filtering blood and activating immune responses.
- B-cells can be activated without Th cells through direct antigen recognition and signal transduction.
Lymphatic Drainage
- The thoracic duct drains lymph into the venous system at the junction of the left subclavian and internal jugular veins.
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Description
Learn about the mechanisms of positive and negative selection in T-cell development. Understand how T-cells with varying affinities for self antigens survive or are eliminated in the thymus.
