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Questions and Answers
What is the definition of hematopoiesis?
What is the definition of hematopoiesis?
The process of forming blood and immune cells from hematopoietic stem cells (HSCs) in the bone marrow.
What are the two main categories of common progenitors that HSCs differentiate into?
What are the two main categories of common progenitors that HSCs differentiate into?
Myeloid progenitors and Lymphoid progenitors.
Which of the following is NOT a characteristic of hematopoietic stem cells (HSCs)?
Which of the following is NOT a characteristic of hematopoietic stem cells (HSCs)?
What is the purpose of VDJ recombination in B cell development?
What is the purpose of VDJ recombination in B cell development?
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Which of these proteins is primarily responsible for initiating VDJ recombination?
Which of these proteins is primarily responsible for initiating VDJ recombination?
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The presence of both CD4 and CD8 markers on a T cell indicates it is in the double positive (DP) stage of development.
The presence of both CD4 and CD8 markers on a T cell indicates it is in the double positive (DP) stage of development.
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What is the main role of CD4+ T cells in the immune system?
What is the main role of CD4+ T cells in the immune system?
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What is autoimmunity?
What is autoimmunity?
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What is a potential consequence of errors during recombination or rearrangement in immune cells?
What is a potential consequence of errors during recombination or rearrangement in immune cells?
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How can researchers determine if a receptor protein is functional?
How can researchers determine if a receptor protein is functional?
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What are the two main mechanisms that the immune system uses to eliminate self-reactive B cells?
What are the two main mechanisms that the immune system uses to eliminate self-reactive B cells?
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T cells develop in the bone marrow.
T cells develop in the bone marrow.
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What is the main difference between HSCs and B/T progenitors?
What is the main difference between HSCs and B/T progenitors?
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What is the function of polymorphonuclear cells in the immune system?
What is the function of polymorphonuclear cells in the immune system?
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Which of the following techniques can be used to visualize specific DNA sequences in cells?
Which of the following techniques can be used to visualize specific DNA sequences in cells?
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What is the main purpose of nuclear pores?
What is the main purpose of nuclear pores?
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Stress-response genes are typically located far away from nuclear pores.
Stress-response genes are typically located far away from nuclear pores.
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What is the purpose of chromatin loops and rosettes in immunoglobulin gene rearrangement?
What is the purpose of chromatin loops and rosettes in immunoglobulin gene rearrangement?
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What is the expected outcome of a FACS analysis on the thymus of a mouse that is E47 knockout (KO)?
What is the expected outcome of a FACS analysis on the thymus of a mouse that is E47 knockout (KO)?
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What are the main characteristics of euchromatin?
What are the main characteristics of euchromatin?
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What is the main function of enhancers in gene expression?
What is the main function of enhancers in gene expression?
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What is the main difference between primary cells and cell lines?
What is the main difference between primary cells and cell lines?
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How can researchers determine if an enlarged thymus is due to inflammation or cancer?
How can researchers determine if an enlarged thymus is due to inflammation or cancer?
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What is the main characteristic of oncogenes?
What is the main characteristic of oncogenes?
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Metastasis is the ability of cancer cells to spread to other parts of the body.
Metastasis is the ability of cancer cells to spread to other parts of the body.
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Study Notes
Hematopoiesis Overview
- Hematopoiesis is the process of forming blood and immune cells from hematopoietic stem cells (HSCs)
- HSCs are multipotent, meaning they can differentiate into all blood cell types
- HSCs have self-renewal, maintaining their population through replication
- Differentiation pathways lead to common progenitors (MPPs)
- MPPs differentiate into Common Myeloid Progenitors (CMPs) and Common Lymphoid Progenitors (CLPs)
- CMPs create macrophages, neutrophils, and other innate immune cells
- CLPs generate B cells, T cells, and NK cells
- Radiation studies on mice injected with HSCs show their regenerative and multipotent abilities
B Cell Development
- Stages: Pro-B → Pre-B → Immature → Mature B cells
- Heavy chain gene rearrangement begins in Pro-B cells
- Pre-B cells express pre-BCR for antigen recognition
- Immature B cells express IgM on their surfaces
- Mature B cells express both IgM and IgD
- B cells achieve diversity through VDJ recombination
- V (variable), D (diversity), and J (joining) segments rearrange to form the variable region of the Ig heavy chain
- Light chain involves only V and J recombination
- RAG proteins are essential for recombination
- Junctional diversity adds nucleotides, enhancing variability
- Antibody production
- B cells differentiate into plasma cells which secrete antibodies
- B cells differentiate into memory cells for long-term immunity
T Cell Development
- Location: T cells originate in the bone marrow but mature in the thymus
- Stages: Pro-T → Pre-T → Double Negative (DN) → Double Positive (DP) → Single Positive (SP)
- Pro-T cells migrate to the thymus
- Pre-T cells begin beta chain rearrangement
- DN cells lack CD4 and CD8 markers
- DP cells express both CD4 and CD8 markers and TCR alpha chain rearranges
- SP cells commit to either CD4 or CD8 lineage
- TCR diversity is achieved through VDJ recombination (beta chain), and VJ recombination (alpha chain)
- Mechanisms of diversity include random mutations and overlapping segments
- RAG proteins and TDT enzyme are crucial for recombination, adding nucleotides to enhance variability.
- CD4 cells are helper T cells and coordinate immune responses
- CD8 cells are cytotoxic T cells and kill infected cells
Proteins and Factors
- Key transcription factors in immune cell maturation include RAG-1/2, E47, and EZA.
- Their roles involve regulating gene expression and development of immune cells.
Immunological Mechanisms
- Testing for autoimmunity involves checking for self-reactive antibodies in immature B cells.
- Gene silencing and epigenetic regulation prevent B cells from becoming T cells.
Experimental Insights
- Chromatin states (euchromatin and heterochromatin) are important, with euchromatin for actively transcribed genes and heterochromatin for inactive regions
- B and T cell gene clusters are spatially organized to ensure lineage-specific transcription.
- Radiation studies demonstrate the regenerative role of HSCs
- Chromosomes are localized in territories; precise gene regulation.
Chromosome Territories and Enhancers
- Chromosome territories are the distinct regions occupied by individual chromosomes within the nucleus.
- Critical Regulatory Elements like promoters and enhancers are located within these territories
- Euchromatin is active transcriptionally, while heterochromatin is inactive.
- Enhancers activate transcription by serving as binding sites for transcription factors, and contribute to regulation, and gene expression.
- Enhancers can be located far from the promoter regions.
Mutations, Tumorigenesis, and Cellular Behavior
- Contact inhibition is crucial for normal cell growth
- Loss of contact inhibition leads to uncontrolled cell growth
- Oncogenes are normal genes that, upon mutation, drive cancer progression
- Metastasis is the spread of cancer cells throughout the body
Summary of Key Cellular Mechanisms
- Primary cells are directly isolated from organisms and have limited growth potential.
- Immortalized cells are mutated or transformed, dividing indefinitely
- Confluency is when cells cover the whole culture plate, stopping cell division without mutation
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