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Questions and Answers
What is a contributing factor to the development of autoimmune diseases?
What is a contributing factor to the development of autoimmune diseases?
What role do MHC genes play in autoimmunity?
What role do MHC genes play in autoimmunity?
How can microbial antigens lead to autoimmune disease?
How can microbial antigens lead to autoimmune disease?
What is a potential outcome of failed self-tolerance?
What is a potential outcome of failed self-tolerance?
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What initiates the autoimmune response after an infection or trauma?
What initiates the autoimmune response after an infection or trauma?
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What aspect of a host affects the induction of tolerance?
What aspect of a host affects the induction of tolerance?
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Which type of antigen structure is more likely to induce tolerance?
Which type of antigen structure is more likely to induce tolerance?
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How do immunosuppressive drugs affect tolerance?
How do immunosuppressive drugs affect tolerance?
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Which of the following correctly distinguishes central tolerance from peripheral tolerance?
Which of the following correctly distinguishes central tolerance from peripheral tolerance?
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What is a significant importance of induced tolerance?
What is a significant importance of induced tolerance?
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What happens to B lymphocytes during central tolerance?
What happens to B lymphocytes during central tolerance?
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Continuous presence of antigen is most likely to result in which of the following?
Continuous presence of antigen is most likely to result in which of the following?
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Which statement about peripheral tolerance is true?
Which statement about peripheral tolerance is true?
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What does immunological tolerance refer to?
What does immunological tolerance refer to?
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Which type of tolerance refers to non-reactivity to self antigens?
Which type of tolerance refers to non-reactivity to self antigens?
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What term describes an antigen that induces tolerance?
What term describes an antigen that induces tolerance?
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What can happen if the mechanisms of immunological tolerance fail?
What can happen if the mechanisms of immunological tolerance fail?
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Which of the following describes induced tolerance?
Which of the following describes induced tolerance?
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What is a common reason for the immune system's non-reactivity to self antigens?
What is a common reason for the immune system's non-reactivity to self antigens?
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How is tolerance induced in the immune system?
How is tolerance induced in the immune system?
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What are the two types of tolerance mentioned?
What are the two types of tolerance mentioned?
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What happens to self-reactive T cells that bind to self antigens in the thymus?
What happens to self-reactive T cells that bind to self antigens in the thymus?
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Which of the following describes clonal anergy in T cells?
Which of the following describes clonal anergy in T cells?
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What role do suppressor T cells play in immune tolerance?
What role do suppressor T cells play in immune tolerance?
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What is receptor editing in B cells primarily associated with?
What is receptor editing in B cells primarily associated with?
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Which mechanism primarily facilitates the central tolerance of T cells?
Which mechanism primarily facilitates the central tolerance of T cells?
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What is autoimmunity fundamentally characterized by?
What is autoimmunity fundamentally characterized by?
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What factors are considered principal in the development of autoimmunity?
What factors are considered principal in the development of autoimmunity?
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Which of the following best explains the concept of peripheral tolerance?
Which of the following best explains the concept of peripheral tolerance?
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Study Notes
Tolerance and Autoimmunity
- Immunological tolerance is unresponsiveness to self-antigens.
- It's the lack of response to antigens.
- The immune system doesn't react against one's own (self) antigens.
- All individuals are tolerant/unresponsive to their self-antigens.
- Tolerance allows for discrimination between self and non-self-antigens.
- Failure of tolerance mechanisms can lead to autoimmunity, where the immune system attacks the body's own cells and tissues.
Objectives
- What is immunological tolerance?
- How many types of tolerance exist?
- How is tolerance induced?
- What's the difference between central and peripheral tolerance?
- What are the mechanisms of autotolerance, and how can it lead to auto-reactivity?
- What is autoimmunity?
Tolerance
- Tolerance refers to the specific immunological non-reactivity to an antigen resulting from a previous exposure to the same antigen.
- Two types of tolerance:
- Autotolerance (self-tolerance, natural tolerance):
- Non-reactivity (unresponsiveness) to self-antigen
- The failure of the immune system to attack the body's own proteins and other antigens
- It's a desired state.
- Induced tolerance:
- Tolerance to non-self antigens.
- Created by manipulating the immune system.
- An antigen that induces tolerance is called a "tolerogen".
- Autotolerance (self-tolerance, natural tolerance):
How Tolerance is Induced
- Tolerance can be induced by administering antigens in specific ways.
- Tolerance can be induced to antigenic components on both soluble proteins and cells (tissues) by injecting these materials into a host.
- The induction of tolerance depends on various factors.
Factors Affecting Tolerance Induction
-
Immunologic maturity of the host:
- Neonates are more easily tolerized than mature hosts.
- Neonates may accept allografts that mature hosts reject.
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Structure and dose of antigen:
- Simple molecules induce tolerance more readily than complex ones.
- Very high or very low doses of antigen can result in "immune paralysis," a form of tolerance.
- Continuous antigen presence helps maintain tolerance.
- Administration of immunosuppressive drugs: Used in transplantation, to enhance tolerance.
- Tolerance can be induced by soluble antigens administered intravenously or orally.
Importance of Induced Tolerance
- Protection against allergic reactions (e.g., food allergies, insect stings).
- Avoidance of graft rejection, allowing transplanted organs to survive.
- Antigen-specific tolerance strategies are used for preventing and treating autoimmune diseases.
Importance of Immunological Tolerance
- Treating immunological diseases
- Treatment of allergies
- Treatment of autoimmune diseases
- Preventing rejection
- Preventing immune responses against newly expressed genes (gene therapy).
Central and Peripheral Tolerance
- Central tolerance: Occurs during development of T and B cells in the thymus and bone marrow.
- Peripheral tolerance: Develops after T and B cells mature and enter peripheral tissues.
Mechanisms of Autotolerance in T Cells
- Clonal deletion (for central tolerance): Self-reactive T cells are deleted or killed (negative selection) in the thymus during development.
- Clonal anergy (for peripheral tolerance): Self-reactive T cells become functionally inactivated outside the thymus due to inappropriate self-antigen presentation, leading to a lack of IL-2 production.
-
Suppressor T cells (regulatory T cells):
- Suppress immune system activity.
- Maintain tolerance to self-antigens.
- Induced by both low and high doses of antigens, acting directly or by cytokine production (e.g., IL-10).
Mechanisms of Autotolerance in B Cells
- Clonal deletion
- Clonal anergy
- Suppressor cells
- Receptor editing: May change the affinity and specificity of B cells due to high soluble antigen levels.
Autoimmunity
- Autoimmunity is an immune response against self-antigens.
- Factors influencing autoimmune development include genetic susceptibility and environmental triggers (e.g., infection).
- Results in production of antibodies against self-antigens or activation of T cells reactive with self-antigens.
- Etiology of human autoimmune diseases is still not fully understood.
Autoimmunity Etiology
- Polygenic: Genetic factors influence susceptibility to autoimmunity, likely by affecting self-tolerance maintenance.
- MHC genes: Genetic variations in MHC genes can affect susceptibility.
- Environmental triggers: Infection, tissue injury, inflammation can promote influx of lymphocytes into tissues and activate self-reactive T cells, causing tissue injury.
Autoimmunity - Other Factors
- Normal encounter of mature T cells with self-antigens presented by resting tissue antigen-presenting cells (APCs) can lead to peripheral tolerance through anergy or deletion.
- Microbes can activate APCs, which then present self-antigens to activate specific T cells, leading to autoimmunity.
- Microbial antigens, due to mimicry, can cross-react with self-antigens.
- Therefore, immune responses initiated by microbes may be directed at self-cells and tissues.
- Some antibodies can cross-react with heart tissue, causing conditions like rheumatic fever.
- Autoimmunity can be triggered by infection or trauma and the release of sequestered antigens, contributing to the failure of self-tolerance and autoimmune disease.
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Description
Explore the concepts of immunological tolerance and its significance in the immune system. This quiz covers types of tolerance, mechanisms of autotolerance, and the transition to autoimmunity. Test your understanding of how the body distinguishes between self and non-self-antigens.
