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Questions and Answers
What inhibitory receptors are highly expressed in anergic cells due to low expression of B7?
Which process may be induced by the coexpression of the death receptors Fas and their ligands FasL in T cells?
Which molecules may Treg cells use to block or remove B7 molecules from APCs?
Which cytokines are produced by Treg cells to inhibit the activation of lymphocytes and other innate immune cells?
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What is the role of TCR complex in the absence of B7 in transmitting signals to T cells?
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What is the main focus of immunological tolerance?
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What is the function of helper CD4+ cells in immune responses to protein antigens?
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Which type of tolerance involves the role of costimulation and Treg cells?
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What triggers autoimmunity according to the text?
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In the normal immune system, what is constantly generated during lymphocyte maturation?
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What role do environmental triggers play in autoimmunity?
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How do mutations in complement proteins C1, C2, C4 contribute to autoimmunity?
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What is molecular mimicry in the context of autoimmunity?
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What is the best-defined death receptor-ligand pair involved in self-tolerance?
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Which protein expressed mainly on activated T cells may block or remove B7 on APCs?
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Which cells are capable of recognizing commensal microbes without reacting against them?
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In which organ do mature lymphocytes recognize but not react against commensal microbes?
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Which mechanism contributes to tolerance against fetal antigens by generating regulatory T cells specific to paternal antigens?
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Which molecule expressed by regulatory T cells may remove B7 molecules on APCs?
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Which cytokines are produced by some regulatory T cells to inhibit the activation of lymphocytes, dendritic cells, and macrophages?
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What happens when signaling from some Toll-like receptors occurs in dendritic cells against commensal microbes?
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Where does tolerance to self antigens not present in primary lymphoid organs occur?
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Which cell type orchestrates virtually all immune responses to protein antigens?
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What is the role of regulatory T cells in peripheral tolerance?
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What may happen if mature T cells recognize self antigens in peripheral tissues without adequate costimulation?
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Study Notes
Immunological Tolerance
- Immunological tolerance is the ability of the immune system to differentiate between self and non-self antigens.
- The immune system is able to react to an enormous variety of microbes but not against self-antigens.
Central Tolerance
- Central tolerance occurs in the thymus and bone marrow.
- It is the process by which developing lymphocytes encounter self-antigens and are either deleted or made tolerant.
- Immature T lymphocytes that recognize self-antigens with high affinity in the thymus undergo apoptosis (negative selection).
- Some self-reactive T cells may differentiate into regulatory T cells (Tregs) that play a role in peripheral tolerance.
Peripheral Tolerance
- Peripheral tolerance occurs in secondary lymphoid organs and peripheral tissues.
- It is the process by which mature T cells recognize self-antigens and are either functionally inactivated (anergy) or deleted.
- Antigen recognition without adequate costimulation results in T cell anergy or death, or makes T cells sensitive to suppression by regulatory T cells.
- Tregs play a crucial role in peripheral tolerance by suppressing autoreactive T cells.
Mechanisms of Tolerance
- Anergy: T cells that recognize self-antigens without adequate costimulation become functionally inactivated.
- Deletion: T cells that recognize self-antigens with high affinity undergo apoptosis.
- Suppression: Tregs suppress autoreactive T cells.
- Receptor editing: T cells that recognize self-antigens may edit their receptors to no longer recognize the self-antigen.
Autoimmunity
- Autoimmunity is an immune response against self-antigens.
- The principal factors in the development of autoimmunity are the inheritance of susceptibility genes and environmental triggers.
- Genetic factors, such as mutations in the AIRE gene, can lead to autoimmune diseases.
- Environmental triggers, such as infections, can also trigger autoimmunity.
Tolerance to Commensal Microbes
- The immune system has to coexist with many commensal microbes that live within the human host.
- Tolerance to commensal microbes is mediated by several mechanisms, including:
- IL-10-producing regulatory T cells
- Unusual property of dendritic cells that leads to inhibition rather than activation
- Other mechanisms that are not yet fully understood
Tolerance to Fetal Antigens
- The immune system of a pregnant female has to accept the presence of a fetus that expresses antigens derived from the father.
- One mechanism of tolerance is the generation of peripheral FoxP3+ regulatory T cells specific for paternal antigens.
- Other mechanisms, such as an abundance of IL-10-producing regulatory T cells, may also play a role in tolerance to fetal antigens.
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