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Questions and Answers
What is the first checkpoint in the T-cell maturation process?
What is the first checkpoint in the T-cell maturation process?
What is the role of the surrogate Ψα chain in T-cell maturation?
What is the role of the surrogate Ψα chain in T-cell maturation?
Which of the following best describes double positive thymocytes?
Which of the following best describes double positive thymocytes?
What role does IL-21 play in the immune system?
What role does IL-21 play in the immune system?
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Which process occurs after TCR recognition of the HLA-peptide complex?
Which process occurs after TCR recognition of the HLA-peptide complex?
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What happens to thymocytes that fail to bind HLA-peptide?
What happens to thymocytes that fail to bind HLA-peptide?
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What initiates the generation of the T-cell receptor during T-cell maturation?
What initiates the generation of the T-cell receptor during T-cell maturation?
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Which other receptors are involved in the activation of CD8 T killer cells?
Which other receptors are involved in the activation of CD8 T killer cells?
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What effect does the successful binding of the Ψα-β dimer to thymic cells have?
What effect does the successful binding of the Ψα-β dimer to thymic cells have?
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What is one method by which CD8 T killer cells can induce cell death in target cells?
What is one method by which CD8 T killer cells can induce cell death in target cells?
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What is the term used to describe the contact area between CD8 killer cells and target cells?
What is the term used to describe the contact area between CD8 killer cells and target cells?
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Which of the following statements about immature T-cells is false?
Which of the following statements about immature T-cells is false?
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What role do dendritic cells and epithelial cells play during thymocyte maturation?
What role do dendritic cells and epithelial cells play during thymocyte maturation?
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Which of the following is NOT a mechanism for CD8 T killer cells to kill target cells?
Which of the following is NOT a mechanism for CD8 T killer cells to kill target cells?
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What is the result of the VDJ rearrangement induced by thymic signals?
What is the result of the VDJ rearrangement induced by thymic signals?
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Which ligand is specifically mentioned as binding to Fas on target cells during the killing process?
Which ligand is specifically mentioned as binding to Fas on target cells during the killing process?
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What is the significance of low affinity binding of TCR to histocompatibility molecules?
What is the significance of low affinity binding of TCR to histocompatibility molecules?
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Which cell surface glycoproteins are expressed by B cells committed to the B cell lineage in the bone marrow?
Which cell surface glycoproteins are expressed by B cells committed to the B cell lineage in the bone marrow?
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What initiates the immediate signaling for granule release in T cells?
What initiates the immediate signaling for granule release in T cells?
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What initiates the proliferation of stem cells during B cell maturation?
What initiates the proliferation of stem cells during B cell maturation?
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Which interleukin is crucial during the early phase of B cell maturation?
Which interleukin is crucial during the early phase of B cell maturation?
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How many new B cells are generated daily, and what proportion typically survive?
How many new B cells are generated daily, and what proportion typically survive?
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Which cytokine is predominantly important in the late phase of B cell maturation?
Which cytokine is predominantly important in the late phase of B cell maturation?
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What is the consequence of TCRs that have a high affinity for self-peptides?
What is the consequence of TCRs that have a high affinity for self-peptides?
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What role does the thymus play in preventing autoimmune diseases?
What role does the thymus play in preventing autoimmune diseases?
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What is a characteristic of DiGeorge Syndrome regarding T-cell development?
What is a characteristic of DiGeorge Syndrome regarding T-cell development?
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In the context of T-cell maturation, what is the function of NOTCH signaling in the thymus?
In the context of T-cell maturation, what is the function of NOTCH signaling in the thymus?
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What is the composition of the thymus primarily made of?
What is the composition of the thymus primarily made of?
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What type of immune cells are specifically stained in the thymus to make mature T cells visible?
What type of immune cells are specifically stained in the thymus to make mature T cells visible?
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What change occurs in the thymus activity from childhood to adulthood?
What change occurs in the thymus activity from childhood to adulthood?
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What peculiar characteristic is observed in the immunity of a patient with no mature T cells and only IgM isotype?
What peculiar characteristic is observed in the immunity of a patient with no mature T cells and only IgM isotype?
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Which cells in the thymus play a crucial role in supporting the development of thymocytes?
Which cells in the thymus play a crucial role in supporting the development of thymocytes?
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What happens to the number of effector T cells during the contraction phase?
What happens to the number of effector T cells during the contraction phase?
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Which CD4 T cell subpopulation is specifically mentioned as part of their differentiation process?
Which CD4 T cell subpopulation is specifically mentioned as part of their differentiation process?
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What is a key characteristic of memory T cells compared to naive T cells?
What is a key characteristic of memory T cells compared to naive T cells?
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How do memory T cells maintain their population levels despite being prone to apoptosis?
How do memory T cells maintain their population levels despite being prone to apoptosis?
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What is a significant factor in the differentiation of T cell subpopulations?
What is a significant factor in the differentiation of T cell subpopulations?
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What could potentially lead to a slower immune response if memory T cells fall below a certain threshold?
What could potentially lead to a slower immune response if memory T cells fall below a certain threshold?
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Which of the following is NOT a property of memory T cells?
Which of the following is NOT a property of memory T cells?
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In terms of survival mechanisms, memory T cells can continue to proliferate due to crossmatching with what?
In terms of survival mechanisms, memory T cells can continue to proliferate due to crossmatching with what?
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What effect does CD45 have on Src kinases recruited to the SMAC area?
What effect does CD45 have on Src kinases recruited to the SMAC area?
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Which component is directly responsible for the opening of Ca2+ channels on the T cell surface?
Which component is directly responsible for the opening of Ca2+ channels on the T cell surface?
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In the Ca pathway, what is the role of calmodulin after binding with Ca2+?
In the Ca pathway, what is the role of calmodulin after binding with Ca2+?
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What is the immediate action of phospholipase C Gamma in the Ca pathway?
What is the immediate action of phospholipase C Gamma in the Ca pathway?
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What role does DAG play in the PKC mediated pathway?
What role does DAG play in the PKC mediated pathway?
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What happens to NFAT-C after it is dephosphorylated by calcineurin?
What happens to NFAT-C after it is dephosphorylated by calcineurin?
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What is the primary function of SLP-76 in the T cell activation process?
What is the primary function of SLP-76 in the T cell activation process?
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Which molecules are crucial for T cell proliferation following the activation of transcription from specific clusters of genes?
Which molecules are crucial for T cell proliferation following the activation of transcription from specific clusters of genes?
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Study Notes
T&B Cell Maturation
- Hematopoietic stem cells differentiate into their common lymphoid progenitor
- Progenitor migrates to thymus for T cell development, bone marrow for B cell development
- Tissue-specific differentiation is regulated by membrane receptor signals, affecting gene transcription
- B cell development involves EBF, E2A, and PAX5 transcriptional factors, leading to BCR rearrangement and creating follicular B cells, marginal zone B cells, or B1 cells
- T cell development involves Notch1 and GATA3, resulting in TCR rearrangement
- Early maturation stages rely on cytokines: IL-4 for B cells and IL-7 for T cells
- Mutations in the cytokine receptor's common γ chain cause X-SCID (lack of B & T cells)
- Rearranging genes coding for the antigen receptor is critical for cell survival and differentiation
- Mutations or defects at this stage can prevent normal development (e.g., Bruton Disease)
Common Maturation Steps
- Early stages involve proliferation driven by cytokines
- Mutations in cytokine receptors can cause immunodeficiencies like X-SCID
- Rearrangement of genes coding for antigen receptors is essential for cell development
- Defects in this stage can lead to diseases like Bruton Disease
Thymus
- Located in the thorax, posterior to the sternum.
- Contains multiple lobes subdivided into trabeculae for structural support.
- Crucial for T-cell development, especially active in childhood
- Activity decreases with age, declining from adolescence into adulthood
T-Cell Maturation
- Immature T cells (CD3-) entering the thymus lack antigen receptors
- Thymic epithelial-stromal cells trigger TCR gene rearrangement
- T cells randomly acquire different TCRs reacting with distinct ligands.
- The first chain to rearrange is usually β;
- Incorrect rearrangement leads to apoptosis.
- Correctly rearranged β-chain followed by surrogate α chain allows expression of receptor on surface
- The resulting signal blocks additional VDJ rearrangements, starting a wave of proliferation for cells with the same β chain
- Double-positive thymocytes (CD3+ CD4+ CD8+) bind HLA-peptides on thymic epithelial cells.
- Unable to bind lead to apoptosis
- Negative selection eliminates thymocytes that bind to self-peptides too strongly
- Thymocytes that pass both selections form single-positive T cells.
B-Cell Maturation
- Virgin B cells emerging from bone marrow are similar to naïve T cells
- Expressed surface markers are CD45 and CD19
- Maturation involves early proliferation in response to cytokines (e.g., IL-3 and IL-4)
- Crucial first step in creating a wide B-cell repertoire.
Pro-B Stage (and activation of genes for BCR)
- Chromatin opening initiates rearrangement processes for heavy chains
- RAG activation is triggered by bone marrow stromal cells
- Recombination of Ig heavy genes occurs
- The surrogate light chain is critical before light chains can be expressed.
Light Chains Activation and gene rearrangement
- B cells try to rearrange the light k chain first, then surrogate λ
- In success, prevents any other gene rearrangement.
- If no success, it implies that cell may undergo apoptosis.
Co-expression of IgM and IgD
- Mature B cells express both IgM and IgD, generated from the same VDJ segment by alternative splicing.
- IgD likely helps in capturing endogenous antigens.
B Cell Differentiation (various B cells)
- Different types of B cells (B1, MZ, and follicular B2) develop from immature B cells
- Location of these cells plays a role (Marginal Zone, Follicle)
- Various surface markers differentiate these cells
B1 Cells
- Arises early in development from both liver and bone marrow.
- 5% of B lymphocytes
- Predominantly found in peritoneal and pleural cavities, where they self-renew
- Receptor diversity is limited compared to other B cells (no TdT)
- CD5 as a marker.
- Function in response to infection and in antibody response
Marginal Zone (MZ) B Cells
- Minor population, derived from B2 cells.
- Primarily resides in splenic marginal zone.
- Activation and survival dependent on Notch receptor/ligand interaction.
- Critical role in responses to blood-borne antigens and in cooperation between innate and adaptive immune responses
Follicular B2 and mature B Cells
- Most prevalent B cell subtype in adults.
- Develop in bone marrow.
- Absence of Notch-2 favors differentiation into these cells
- High antibody specificity and diversity.
T Cell Activation
- Naive T cells circulate in the peripheral tissues, encountering the antigen for the first time The antigen is presented by dendritic cells and other APCs via MHC molecules.
- Co-stimulatory signals are needed alongside TCR signaling
- Activation triggers T-cell proliferation and differentiation into effector or memory cells
- Effector T cells become involved in various immune responses (killing infected cells, modulating immune responses
T-cell activation process
- TCR binding to MHC-antigen complex.
- Co-stimulatory signals (e.g., CD28-B7 interaction)
- Cytokine stimulation (e.g., IL-2).
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Description
This quiz covers the intricate process of T and B cell maturation, detailing the differentiation of hematopoietic stem cells, key transcription factors involved, and the impact of cytokines on development. It also highlights critical mutations that can hinder normal immune cell formation. Test your understanding of these vital immunological concepts.
