Immune tolerance is the inhibition or absence of an immune response leaving only protective and beneficial immunity intact. Tolerance reduces response to both self and non-self antigens, which are substances which stimulate antibody production.
Tolerance breakdown causes immune disease; failed self-tolerance causes incorrect identification of self as foreign, causing autoimmune disease. Failure of induced tolerance causes overzealous identification of harmless foreign substances as a threat, causing hypersensitivities.
This essay explores the immunological mechanisms by which tolerance occurs, and their role in preventing the development of allergic disease.
Table of Contents
Allergy
Central Tolerance
T-cell tolerance
B-cell Tolerance
Peripheral Tolerance
Anergy
Deletion
B cell antibody production
Immune Deviation
Regulatory Lymphocytes
Regulatory T cells: Treg, Tr1, Th3
Regulatory B cells: Breg, Br1, Br3
Innate Immune System: Dendritic cells
Immune Privilege
Tolerance in Pregnancy
Induced Tolerance
Conclusion
Research Objectives and Key Topics
This work examines the complex immunological mechanisms that establish and maintain immune tolerance to self and foreign antigens. The primary focus is to analyze how the breakdown of these regulatory processes contributes to the development of allergic diseases and how various tolerance pathways—ranging from central and peripheral mechanisms to cellular regulation—function to prevent hypersensitivity reactions.
- Immunological mechanisms of central and peripheral tolerance
- Pathophysiology of allergy and IgE-mediated hypersensitivity
- Regulatory roles of T cells (Treg, Tr1, Th3) and B cells (Breg)
- Contribution of dendritic cells to immune regulation and tolerance induction
- Therapeutic approaches to restore tolerance via allergen-specific immunotherapy
Extract from the Book
Central Tolerance
Central tolerance, first theorised in 1959 by Joshua Lederberg, is the induction of lymphocyte apoptosis or anergy within primary lymphoid organs; bone marrow for B cells and the thymus for T cells. It prevents self-reactive lymphocytes entering the circulation.
T-cells respond to antigens in the context of major histocompatibility complex (MHC) on antigen presenting cells (APCs). Activation requires co-stimulation of both the cell-surface T cell receptor (TCR) and CD28 by the MHC and B7 on the APC, with lack of co-stimulatory CD28 engagement causing anergy.
Within the thymus, cells are retained or excluded according to their receptor affinity for peptide antigen, leaving a pool of functionally useful T-cells, with ~98% dying during selection. Firstly, pluripotent haemopoietic stem cells from the bone marrow produce precursor CD4-CD8- T-cells which seed in the thymus from week eight of development. β repertoire selection ensures thymocytes with a functional TCR β-chain survive and divide, with TCRα gene rearrangement and differentiation to CD4+CD8+ αβ+ cells.
Positive selection of thymocytes which have self-MHC binding, during MHC presentation by thymic DCs, occurs and thymocytes which fail die ‘by neglect’. Negative selection occurs during overly strong responses to MHC, resulting in apoptosis, ensuring self tolerance.
Summary of Chapters
Allergy: Explains the pathophysiology of hypersensitivity reactions, specifically focusing on Type I and the role of IgE and Th2 cells in allergic responses.
Central Tolerance: Describes the processes in the thymus and bone marrow that eliminate self-reactive T and B cells to prevent autoimmunity.
Peripheral Tolerance: Details the mechanisms that control auto-reactive lymphocytes that have escaped central tolerance, including anergy, deletion, and antibody production regulation.
Immune Deviation: Discusses how T cells differentiate into Th1 or Th2 phenotypes and the influence of cytokine balance on allergic versus protective immune responses.
Regulatory Lymphocytes: Analyzes the essential role of regulatory T cells (Tregs) and B cells (Bregs) in suppressing excessive immune responses and maintaining tolerance.
Innate Immune System: Dendritic cells: Explores how dendritic cells function as key mediators that can either initiate immune activation or promote tolerogenic environments.
Immune Privilege: Explains organ-specific protection mechanisms that limit immune access to sensitive tissues.
Tolerance in Pregnancy: Examines how the maternal immune system adjusts to accept the semi-allogeneic fetus.
Induced Tolerance: Summarizes various immunotherapy methods used to treat allergies by re-inducing immunological tolerance.
Conclusion: Synthesizes the importance of the integrated network of immune cells and mediators in protecting the body from both internal and external threats.
Keywords
Immune tolerance, Allergy, Hypersensitivity, T-cells, B-cells, Dendritic cells, Tregs, Immunotherapy, Cytokines, Autoimmunity, IgE, Anergy, Peripheral tolerance, Central tolerance, Immune deviation
Frequently Asked Questions
What is the primary scope of this work?
This work explores the different biological pathways that allow the immune system to distinguish between harmful and harmless substances, with a specific focus on the mechanisms of tolerance that prevent allergic disease.
What are the central thematic fields covered?
The document covers immunology, specifically focusing on immune tolerance, the maturation of T and B lymphocytes, regulatory cell populations, dendritic cell function, and the clinical application of immunotherapy.
What is the core objective of the research?
The core objective is to identify and describe the various mechanisms through which immune tolerance is maintained and to investigate how the failure of these processes leads to allergic diseases and hypersensitivities.
Which scientific methods are discussed in the context of tolerance?
The text reviews biological mechanisms such as clonal anergy, activation-induced apoptosis (deletion), cytokine-mediated suppression, and the specific role of regulatory lymphocytes and dendritic cells in modulating immune responses.
What does the main body address?
The main body systematically details central and peripheral tolerance, the roles of Th1/Th2 balance, regulatory lymphocyte subsets, dendritic cell-mediated regulation, and current methods for inducing tolerance via immunotherapy.
Which keywords define this document?
Key terms include immune tolerance, IgE-mediated allergy, regulatory T cells, dendritic cells, immunotherapy, and cytokine-mediated immune deviation.
How does the "hygiene hypothesis" relate to the content?
The document mentions that the hygiene hypothesis suggests early microbial exposure may shift immune responses from a Th2 phenotype toward a more regulatory or Th1 phenotype, mediated by Tregs.
What is the role of Foxp3 in this context?
Foxp3 is identified as the primary transcription factor for regulatory T cells; its absence or dysfunction is linked to severe autoimmune and allergic conditions, such as IPEX syndrome.
How is the B cell system compared to the T cell system?
The document notes that the B cell system mirrors the T cell system, utilizing specific regulatory B cell subsets (Bregs) that express inhibitory cytokines and sometimes Foxp3 to modulate inflammation and maintain tolerance.
What are the different types of allergen-specific immunotherapy mentioned?
The work details four primary methods: Subcutaneous (SCIT), Intralymphatic (ILIT), Sublingual (SLIT), and Transcutaneous (TCIT) immunotherapy, comparing their administration, effectiveness, and common side effects.
- Quote paper
- Charlotte Leahy (Author), 2014, The different mechanisms through which immune tolerance to antigens can occur, and their relative importance in preventing the development of allergic disease, Munich, GRIN Verlag, https://www.grin.com/document/352611
