Podcast
Questions and Answers
What determines whether a T cell undergoes apoptosis during negative selection?
What determines whether a T cell undergoes apoptosis during negative selection?
Which mechanism is crucial for preventing autoimmunity during T cell development?
Which mechanism is crucial for preventing autoimmunity during T cell development?
During which process do naive B cells interact with self antigens in the bone marrow?
During which process do naive B cells interact with self antigens in the bone marrow?
What is the consequence of a T cell binding too tightly to self antigens in the thymic cortex?
What is the consequence of a T cell binding too tightly to self antigens in the thymic cortex?
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Which process allows a T cell to become ‘educated’ to self MHC?
Which process allows a T cell to become ‘educated’ to self MHC?
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What primarily happens to B cells that show a strong response to self antigens?
What primarily happens to B cells that show a strong response to self antigens?
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What characterizes the state of peripheral tolerance?
What characterizes the state of peripheral tolerance?
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Which statement about anergy in T cells is true?
Which statement about anergy in T cells is true?
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What is the main function of thymic dendritic cells during T cell development?
What is the main function of thymic dendritic cells during T cell development?
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What is the process by which T cells that strongly recognize self-antigens are eliminated during their development?
What is the process by which T cells that strongly recognize self-antigens are eliminated during their development?
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Which mechanism describes the end of T-cell activation due to lack of costimulatory signals?
Which mechanism describes the end of T-cell activation due to lack of costimulatory signals?
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What type of tolerance involves mechanisms that act upon mature lymphocytes in peripheral tissues?
What type of tolerance involves mechanisms that act upon mature lymphocytes in peripheral tissues?
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What is the specific term for the process that ensures that T cells able to react with MHC molecules are selected for further maturation?
What is the specific term for the process that ensures that T cells able to react with MHC molecules are selected for further maturation?
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Which of the following best describes a situation where the immune system fails to respond to a particular antigen due to lack of recognition?
Which of the following best describes a situation where the immune system fails to respond to a particular antigen due to lack of recognition?
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What term refers to the selective elimination of lymphocytes that express receptors recognizing self-antigens during their development?
What term refers to the selective elimination of lymphocytes that express receptors recognizing self-antigens during their development?
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Which of the following processes is a form of peripheral tolerance associated with regulatory T cells that reduce immune responses?
Which of the following processes is a form of peripheral tolerance associated with regulatory T cells that reduce immune responses?
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The capacity of a T cell to survive and proliferate is diminished if it recognizes self-antigens without receiving proper activation signals. This phenomenon is known as what?
The capacity of a T cell to survive and proliferate is diminished if it recognizes self-antigens without receiving proper activation signals. This phenomenon is known as what?
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Which process primarily occurs in the bone marrow and thymus to ensure that potentially harmful self-reactive lymphocytes are eliminated?
Which process primarily occurs in the bone marrow and thymus to ensure that potentially harmful self-reactive lymphocytes are eliminated?
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What is the term used for the removal of T cells that do not successfully interact with MHC molecules during development?
What is the term used for the removal of T cells that do not successfully interact with MHC molecules during development?
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What mechanism primarily assists in the clonal deletion of T-cells in the peripheral tolerance process?
What mechanism primarily assists in the clonal deletion of T-cells in the peripheral tolerance process?
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Which of the following statements accurately describes the expression of Fas and Fas Ligand on T-cells?
Which of the following statements accurately describes the expression of Fas and Fas Ligand on T-cells?
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The interaction between which two molecules is crucial for inducing apoptosis in T-cells during an immune response?
The interaction between which two molecules is crucial for inducing apoptosis in T-cells during an immune response?
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What potential role do some tumor cells play in relation to T-cell activation through the secretion of Fas Ligand?
What potential role do some tumor cells play in relation to T-cell activation through the secretion of Fas Ligand?
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In what context does peripheral tolerance primarily occur concerning T-cells?
In what context does peripheral tolerance primarily occur concerning T-cells?
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What mechanism primarily ensures that B cells do not react against self-antigens during their development?
What mechanism primarily ensures that B cells do not react against self-antigens during their development?
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Which of the following describes the process when T-cells become non-responsive instead of being killed?
Which of the following describes the process when T-cells become non-responsive instead of being killed?
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Which scenario is an example of 'ignorance' in peripheral tolerance?
Which scenario is an example of 'ignorance' in peripheral tolerance?
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What is the role of receptor editing in B cell central tolerance?
What is the role of receptor editing in B cell central tolerance?
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What occurs when a CD4 T-cell binds to MHC class II without engagement of CD28?
What occurs when a CD4 T-cell binds to MHC class II without engagement of CD28?
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What type of immune structure is typically considered to be immunoprivileged?
What type of immune structure is typically considered to be immunoprivileged?
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Which statement best characterizes central tolerance in T cell development?
Which statement best characterizes central tolerance in T cell development?
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Which cytokines are primarily secreted by T-Reg cells to inhibit other immune cells?
Which cytokines are primarily secreted by T-Reg cells to inhibit other immune cells?
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What is the primary function of apoptosis in the context of clonal deletion?
What is the primary function of apoptosis in the context of clonal deletion?
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What is the role of CTLA-4 in T-cell activation?
What is the role of CTLA-4 in T-cell activation?
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Which of the following mechanisms is NOT typically associated with peripheral tolerance?
Which of the following mechanisms is NOT typically associated with peripheral tolerance?
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Natural T-reg cells primarily develop in which location?
Natural T-reg cells primarily develop in which location?
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Defective T-reg cells are strongly associated with which of the following conditions?
Defective T-reg cells are strongly associated with which of the following conditions?
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How do regulatory T-cells induce apoptosis in highly-activated T-cells?
How do regulatory T-cells induce apoptosis in highly-activated T-cells?
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What term describes the inability of certain T-cells to effectively engage with self-antigens due to regulatory mechanisms?
What term describes the inability of certain T-cells to effectively engage with self-antigens due to regulatory mechanisms?
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What is an example of a specialized T-reg cell that functions without expressing FoxP3?
What is an example of a specialized T-reg cell that functions without expressing FoxP3?
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What physiological mechanism prevents T-cells from becoming activated in the presence of self-antigens?
What physiological mechanism prevents T-cells from becoming activated in the presence of self-antigens?
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What characterizes induced T-reg cells compared to natural T-reg cells?
What characterizes induced T-reg cells compared to natural T-reg cells?
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Study Notes
Immune Cell Development: Mechanisms Underlying Central and Peripheral Tolerance
- Immune responses must be carefully undertaken, as immune system cells can damage the host.
- A response to self-antigens is called autoimmunity, causing tissue damage.
- Self-tolerance is needed to prevent autoimmune diseases.
- Central tolerance (occurring in developing T and B cells) and peripheral tolerance (occurring in mature lymphocytes) are mechanisms to achieve this.
Session Aims
- Understand and explain different forms of immune tolerance.
- Explain some forms of autoimmunity.
Before We Start
- Immune system cells have the ability to damage the host.
- Autoimmunity is a response to self-antigens, resulting in tissue damage.
- Self-tolerance is needed for the prevention of autoimmune diseases.
- Central tolerance (developing T and B cells)
- Peripheral tolerance (mature lymphocyte repertoire)
Immune Tolerance
- Recognises self, preventing attack on self-antigens.
- Negative selection (clonal deletion):
- B cells in bone marrow
- T cells in thymus
- Cells reacting with self are destroyed (apoptosis).
- Autoimmunity:
- Cells escaping negative selection.
Tolerance Mechanisms
- Central Tolerance (Deletion/Suppression)
- Peripheral Tolerance (Ignorance/Anergy/Suppression).
Central Selection: Generation of T Cells
- T cell development stages are depicted through an illustration.
- Bone marrow → Thymus → Secondary Lymphoid Organs
Maturation of T-Cells: Steps to Prevent Autoimmunity
- T cell receptor gene rearrangements
- Positive selection (MHC interaction): T cells interacting with MHC molecules survive, otherwise they die.
- Negative selection (self-antigen interaction): T cells interacting with self-antigens undergo apoptosis.
Central Selection: B Cells
- Naive B cells (not exposed to antigens) have IgM on their membrane.
- Self-antigens are presented by stromal cells in bone marrow.
- Apoptosis (clonal deletion) or receptor editing happens, altering B cell specificity.
- Other tolerance mechanisms (anergy, etc.) exist.
Peripheral Tolerance
- Central tolerance processes are limited.
- Auto-reactive immune cells can escape and circulate in the periphery.
- Peripheral tolerance mechanisms are needed.
Peripheral Tolerance: Ignorance
- Some tissues (e.g. brain, eyes) are inaccessible to immune cells due to barriers.
- In some cases, self-antigens are present at low rates, allowing for their avoidance.
- Trauma can release these antigens to generate an immune response.
Peripheral Tolerance: Anergy
- Killing self-reactive T cells isn't always ideal.
- Some self-reactive T cells can be made non-responsive to antigens by non-professional APCs.
- APCs deliver signals to naive T cells.
Peripheral Tolerance: Suppression
- Regulatory T cells (Treg cells) regulate other immune cells.
- Two main classes:
- Induced Treg cells (adaptive/peripheral)
- Natural Treg cells (thymic/naturally occurring)
- Treg cells use mechanisms to suppress T-cell responses.
- Release of cytokines (e.g., TGF-β, IL-10)
- Detection and suppression of self-reactive T cells
- Using FasL for apoptosis induction
Peripheral Tolerance: Clonal Deletion
- Activation-induced cell death (apoptosis): T cells express death receptors (Fas) with FasL interactions to regulate their own activation.
- Fas-FasL interactions are important to terminate T-cell proliferation during autoimmune reactions or after pathogen clearance.
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Description
Explore the mechanisms of central and peripheral tolerance in the immune system. This quiz delves into how self-tolerance is vital for preventing autoimmune diseases and ensures that immune responses do not harm the host. Test your understanding of these crucial immune processes.
