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Questions and Answers
What is the primary function of the innate immune response?
What is the primary function of the innate immune response?
Why is the adaptive immune response considered to have memory?
Why is the adaptive immune response considered to have memory?
Where do T cells complete their development?
Where do T cells complete their development?
What does lymphopoiesis aim to achieve?
What does lymphopoiesis aim to achieve?
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What happens to the thymus as one ages?
What happens to the thymus as one ages?
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What is the main distinction between the innate and adaptive immune responses?
What is the main distinction between the innate and adaptive immune responses?
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How are B cells matured after their initial development?
How are B cells matured after their initial development?
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What are the key cells of the adaptive immune response?
What are the key cells of the adaptive immune response?
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What is the primary purpose of positive selection in T cell development?
What is the primary purpose of positive selection in T cell development?
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What role does the autoimmune regulator gene AIRE play in negative selection?
What role does the autoimmune regulator gene AIRE play in negative selection?
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What determines whether a DP T cell downregulates CD4 or CD8?
What determines whether a DP T cell downregulates CD4 or CD8?
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After successful positive selection, what type of T cell does a DP cell become?
After successful positive selection, what type of T cell does a DP cell become?
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In the context of T cell development, what process occurs after the rearrangement of the beta chain?
In the context of T cell development, what process occurs after the rearrangement of the beta chain?
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What is the function of the T cell receptor (TCR) in relation to peptides and MHC?
What is the function of the T cell receptor (TCR) in relation to peptides and MHC?
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Which type of cells are responsible for presenting antigens to mature T cells in secondary lymphoid organs?
Which type of cells are responsible for presenting antigens to mature T cells in secondary lymphoid organs?
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What is the immediate fate of a DP cell that binds strongly to a self-antigen during negative selection?
What is the immediate fate of a DP cell that binds strongly to a self-antigen during negative selection?
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Which chain rearrangement occurs first during T cell development?
Which chain rearrangement occurs first during T cell development?
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How does the thymus contribute to T cell development?
How does the thymus contribute to T cell development?
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What is the role of MHC molecules in T cell development?
What is the role of MHC molecules in T cell development?
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During which stage is a T cell considered to be double negative?
During which stage is a T cell considered to be double negative?
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What signifies the transition of a DN1 cell to a DN2 cell?
What signifies the transition of a DN1 cell to a DN2 cell?
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Which chain of the T cell receptor is assembled first?
Which chain of the T cell receptor is assembled first?
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What is the significance of allelic exclusion during T cell development?
What is the significance of allelic exclusion during T cell development?
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What happens to a T cell that fails to express a functional T cell receptor?
What happens to a T cell that fails to express a functional T cell receptor?
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What is the function of interleukin 7 (IL-7) in T cell maturation?
What is the function of interleukin 7 (IL-7) in T cell maturation?
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Which proteins are critical for the recombination of the T cell receptor gene segments?
Which proteins are critical for the recombination of the T cell receptor gene segments?
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How many variable gene segments are typically present in the alpha chain of a T cell receptor?
How many variable gene segments are typically present in the alpha chain of a T cell receptor?
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At what stage does a T cell express both CD4 and CD8 on its surface?
At what stage does a T cell express both CD4 and CD8 on its surface?
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What is the primary function of the invariant pre-T alpha chain?
What is the primary function of the invariant pre-T alpha chain?
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Which of the following stages involves rearranging the alpha chain after the beta chain is formed?
Which of the following stages involves rearranging the alpha chain after the beta chain is formed?
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Which combination represents a unique structure of a T cell receptor?
Which combination represents a unique structure of a T cell receptor?
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Which cells are involved in antigen presentation to developing T cells?
Which cells are involved in antigen presentation to developing T cells?
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At which developmental stage is a T cell primarily focused on creating a functional receptor?
At which developmental stage is a T cell primarily focused on creating a functional receptor?
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What is the main function of RAG1 and RAG2 during T cell maturation?
What is the main function of RAG1 and RAG2 during T cell maturation?
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At which stages are RAG1 and RAG2 predominantly active in T cell development?
At which stages are RAG1 and RAG2 predominantly active in T cell development?
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Which of the following accurately describes the checkpoints in T cell development involving RAG1 and RAG2?
Which of the following accurately describes the checkpoints in T cell development involving RAG1 and RAG2?
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What occurs immediately after RAG1 and RAG2 introduce double-strand breaks in the DNA?
What occurs immediately after RAG1 and RAG2 introduce double-strand breaks in the DNA?
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Which phases are included in the double-negative (DN) stage of T cell development?
Which phases are included in the double-negative (DN) stage of T cell development?
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Which of the following best explains the importance of TCR diversity generated by V(D)J recombination?
Which of the following best explains the importance of TCR diversity generated by V(D)J recombination?
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What role do RAG1 and RAG2 specifically play in TCR gene rearrangement?
What role do RAG1 and RAG2 specifically play in TCR gene rearrangement?
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What is the consequence of unsuccessful TCRβ chain recombination in thymocytes?
What is the consequence of unsuccessful TCRβ chain recombination in thymocytes?
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Study Notes
Immune Response
- Innate immune response is non-specific, but immediate.
- Adaptive immune response is targeted for each invader, but takes time to activate.
- Adaptive immunity has memory, which allows for quicker and stronger responses.
Lymphopoiesis
- Lymphopoiesis produces diverse lymphocytes, each with a unique antigen receptor.
- It eliminates self-reactive lymphocytes to prevent autoimmune diseases.
- Hematopoietic stem cells mature into common lymphoid progenitor cells.
- Common lymphoid progenitors differentiate into B cells and T cells.
B Cell Development
- B cells develop in the bone marrow, maturing in the spleen.
T Cell Development
- T cells mature in the thymus, a fatty organ that shrinks with age, leading to decreased cell-mediated immunity.
- Thymus has an outer cortex and inner medulla.
- Epithelial cells and dendritic cells present antigens to developing T cells on MHC molecules.
- T cell receptors (TCR) only bind peptide antigens when presented on MHC molecules.
- TCRs are composed of an alpha chain and a beta chain, each made of V, D, and J gene segments.
- Multiple V, D, and J segments allow for many unique combinations of TCRs.
- T cell development occurs in three stages: Double negative, double positive, and single positive.
Double Negative (DN) Stage
- DN stage cells express neither CD4 nor CD8.
- DN stage progresses through four steps: DN1, DN2, DN3, DN4.
- DN2 cells express Rag-1 and Rag-2 enzymes, which initiate VDJ recombination.
- VDJ recombinase rearranges D-J segments on both chromosomes, with only one chromosome successfully rearranging.
- DN3 cells successfully join D and J segments.
- DN4 cells attach V segments to D-J segments, forming a complete beta chain.
Double Positive (DP) Stage
- DP stage cells express both CD4 and CD8.
- They rearrange the alpha chain while retaining the same beta chain.
- DP cells undergo positive selection, ensuring they recognize MHC molecules.
- Positive selection involves preserving T cells that recognize the individual's own MHC.
- DP cells also undergo negative selection, eliminating self-reactive T cells.
- AIRE (autoimmune regulator gene) allows thymic epithelial cells to express body-wide antigens for negative selection.
Single Positive (SP) Stage
- SP stage cells downregulate either CD4 or CD8.
- CD4 downregulation leads to CD8+ T cells.
- CD8 downregulation leads to CD4+ T cells.
- SP stage cells are naive T cells, ready to encounter antigens in lymph nodes or spleen.
- Mature T cells are released into the periphery, ready to respond to infections.
Summary
- T cell development in the thymus ensures the production of functional T cells that can recognize antigens and respond effectively to infections.
- This process is a complex series of steps, involving gene rearrangement, selection, and maturation, ensuring the generation of a diverse yet safe repertoire of T cells.
RAG1 and RAG2: Key Players in T Cell Development
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RAG1 and RAG2 are crucial enzymes responsible for V(D)J recombination, a process that generates diversity in the T cell receptor (TCR).
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V(D)J recombination rearranges the variable (V), diversity (D), and joining (J) segments of the TCR genes, creating unique receptors.
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This diversity is essential for the adaptive immune system's ability to recognize a vast array of pathogens.
The Double-Negative (DN) Stage
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The DN stage of T cell development involves thymocytes that do not express the co-receptors CD4 or CD8.
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The DN stage is divided into four phases: DN1, DN2, DN3, and DN4.
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RAG1 and RAG2 are most active in the DN2 and DN3 stages, facilitating TCRβ chain recombination.
Key Functions of RAG1 and RAG2
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RAG1 and RAG2 recognize specific DNA sequences flanking the V, D, and J gene segments and introduce double-strand breaks.
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Other proteins repair and recombine these segments to form a functional TCRβ chain.
Checkpoints in T Cell Development
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Successful TCRβ chain recombination, aided by RAG1 and RAG2, is a critical checkpoint at the DN3 stage.
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If recombination is successful, the thymocyte continues development; otherwise, it may undergo apoptosis.
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Description
Test your knowledge on the basics of the immune response, including innate and adaptive immunity, lymphopoiesis, and the development of B and T cells. This quiz covers how the immune system functions and the importance of memory in adaptive immunity.