Immunological Tolerance and Helper T Cells
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Questions and Answers

What is the main difference between natural tolerance and induced tolerance?

  • Natural tolerance is a passive response, whereas induced tolerance is an active manipulation of the immune system. (correct)
  • Natural tolerance prevents autoimmune diseases, while induced tolerance focuses solely on organ transplants.
  • Natural tolerance occurs without any immune response, unlike induced tolerance which still involves immune recognition.
  • Natural tolerance involves only self-antigens, while induced tolerance involves only external antigens.

Why is T cell tolerance considered more important than B cell tolerance?

  • B cells can produce antibodies without T cell assistance.
  • T cells only recognize self-antigens while B cells can recognize both self and non-self.
  • B cells fail to activate in the absence of T cell help for most antigens. (correct)
  • B cells represent a smaller population than T cells in the immune response.

Which type of helper T cell is primarily involved in combating intracellular pathogens?

  • Tfh
  • Th17
  • Th2
  • Th1 (correct)

How does Th2 assist B cells in the immune response?

<p>By promoting the production of IgE antibodies and certain subclasses of IgG. (B)</p> Signup and view all the answers

What role do Tfh cells play in the immune system?

<p>They help B cells develop into antibody-secreting plasma cells in lymphoid follicles. (B)</p> Signup and view all the answers

What function does Th17 primarily serve in the immune system?

<p>They protect mucosal surfaces against extracellular bacteria. (B)</p> Signup and view all the answers

Which statement correctly describes immunological tolerance?

<p>It is a complex active process that can be induced or natural. (A)</p> Signup and view all the answers

What can result from a failure in immunological tolerance towards self-antigens?

<p>Autoimmune diseases due to the immune system attacking body proteins. (C)</p> Signup and view all the answers

What is the main reason that some antigens are not detected by the immune system?

<p>They may appear in very low concentration. (B)</p> Signup and view all the answers

What occurs during clonal deletion in T cells?

<p>Functionally immature cells undergo a programmed cell death. (B)</p> Signup and view all the answers

Which process leads to the inability of T cells to respond to an antigen?

<p>Clonal anergy (B)</p> Signup and view all the answers

What triggers receptor editing in B cells?

<p>Binding to soluble antigens with very low affinity. (B)</p> Signup and view all the answers

What is the role of anti-idiotype antibodies in the immune response?

<p>Inhibit immune response to specific antigens. (A)</p> Signup and view all the answers

Which statement correctly describes suppressor T cells (Regulatory T cells)?

<p>They produce cytokines like TGF-β and IL-10. (B)</p> Signup and view all the answers

What can lead to the termination of experimentally induced tolerance?

<p>Immunization with cross-reactive antigens. (A)</p> Signup and view all the answers

Which characteristic is associated with regulatory T cells?

<p>They express high levels of CD25 but not other markers of activation. (C)</p> Signup and view all the answers

What is the primary function of central tolerance in the immune system?

<p>To eliminate autoreactive lymphocytes (A)</p> Signup and view all the answers

During which phase do T cells undergo positive selection?

<p>In the thymic cortex (A)</p> Signup and view all the answers

What happens to immature B cells that strongly bind self peptides in the bone marrow?

<p>They are signaled to apoptosis (C)</p> Signup and view all the answers

Which type of tolerance occurs after lymphocytes exit primary lymphoid organs?

<p>Peripheral tolerance (C)</p> Signup and view all the answers

What role do transcriptional regulators AIRE and Fezf2 play in T cell tolerance?

<p>Promoting the expression of self tissue antigens (D)</p> Signup and view all the answers

Which mechanism of peripheral tolerance involves the inactivation of self-reactive T cells?

<p>Clonal anergy (B)</p> Signup and view all the answers

What is indicated by the term 'tolerogen'?

<p>An antigen that induces tolerance (B)</p> Signup and view all the answers

What occurs during the process of receptor editing in B cells?

<p>B cells rearrange genes to develop a new BCR (C)</p> Signup and view all the answers

Why is T cell tolerance generally longer lasting than B cell tolerance?

<p>T cell tolerance is more robustly maintained (B)</p> Signup and view all the answers

Which statement accurately differentiates between central and peripheral tolerance?

<p>Central tolerance primarily involves negative selection of lymphocytes. (A)</p> Signup and view all the answers

What is a main consequence of the clonal deletion process?

<p>Prevention of auto-reactive T and B cells (A)</p> Signup and view all the answers

How does ignorance contribute to immunological tolerance?

<p>It permits the presence of self-reactive cells without activation. (D)</p> Signup and view all the answers

Which process leads to the death of T cells that cannot bind to MHC complexes?

<p>Clonal deletion (B)</p> Signup and view all the answers

Which method is NOT involved in inducing peripheral tolerance?

<p>Receptor editing (D)</p> Signup and view all the answers

Flashcards

Immunological Tolerance

The immune system's inability to mount an immune response against a specific antigen. It can be natural or induced.

Natural Tolerance

The immune system's natural lack of response to its own proteins and antigens. Prevents autoimmune diseases.

Induced Tolerance

The immune system's ability to be trained to ignore specific external antigens, like allergens or transplanted organs.

Th1 Helper T Cell

A type of Helper T cell that assists both cell-mediated and antibody-mediated immunity. Crucial for fighting intracellular pathogens like viruses and bacteria.

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Th2 Helper T Cell

A type of Helper T cell that primarily helps B cells produce antibodies. Important for fighting extracellular pathogens like bacteria.

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Tfh Helper T Cell

A type of Helper T cell that provides help to B cells in lymph nodes, enabling them to become antibody-secreting plasma cells. The most abundant Helper T cell.

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Th17 Helper T Cell

A type of Helper T cell that protects surfaces like skin and intestines from extracellular bacteria.

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Epitope

A specific part of an antigen that an antibody binds to. This is crucial for targeting a specific antigen.

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Antigenic Ignorance

The immune system's failure to recognize an antigen due to its low concentration, making it undetectable by lymphocytes.

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Antigen Sequestration

Antigens shielded from the immune system in privileged sites like the eye, central nervous system, and testes. These sites are typically protected by barriers that limit immune cell access.

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Clonal Deletion

A process of programmed cell death that eliminates self-reactive T cells during their development in the thymus. This ensures that the immune system does not attack the body's own cells.

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Clonal Anergy

A state where autoreactive T cells become unresponsive to antigens because they lack the necessary co-stimulatory signals. It prevents autoimmune reactions.

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Receptor Editing

A mechanism where B cells encountering excessive soluble antigens modify their antigen-binding receptors through DNA recombination, changing their specificity to avoid recognizing self-antigens.

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Anti-Idiotype Antibodies

Antibodies specifically targeting the unique receptors of other lymphocytes. They can suppress immune responses to specific antigens by preventing receptor-antigen binding.

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Termination of Tolerance

Breaking down tolerance. This can be achieved by factors like prolonged absence of antigen exposure, immune system damage, or exposure to cross-reactive antigens.

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Suppressor T Cells (Regulatory T Cells)

T cells that suppress immune responses. They can directly suppress B and T cells or indirectly through cytokine production. They play a crucial role in maintaining immune tolerance.

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Central tolerance (Negative selection)

The process of eliminating developing T or B lymphocytes that react with self antigens. This ensures the immune system doesn't attack the body's own cells.

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Function of central tolerance

Mature B cells and T cells do not recognize self antigens as foreign invaders due to this process. Immune cells learn to ignore their own body's components.

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T cell tolerance key concept

T cells have to recognize self MHC molecules with non-self peptides. They need to bind MHC but not get overly stimulated by self antigens.

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Positive selection of T cells

T cells are checked for their ability to bind peptide-MHC complexes. If they can't bind, they die. These cells are then selected for survival based on their ability to bind MHC.

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Negative selection of T cells

T cells are checked for their affinity to self. If they bind self peptides too strongly, they are signaled to die. This ensures T cells don't attack self.

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Mature naïve T cell development

T cells that successfully pass positive and negative selection develop into mature naïve T cells. They are ready to encounter antigens and fight off infections.

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Peripheral tolerance

A state of non-reactivity towards self. This ensures that immune cells that have escaped central tolerance are prevented from causing autoimmune reactions.

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T-cell anergy

A mechanism of peripheral tolerance where self-reactive T cells are deactivated, preventing them from causing autoimmune reactions.

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Regulatory T cells

A type of immune cell responsible for suppressing immune responses and maintaining tolerance. They can help control autoimmunity.

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Tolerogen

An antigen that induces tolerance. It effectively prevents the immune system from attacking the specific antigen.

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Induction of tolerance in T cells

Relatively smaller amounts of tolerogen are needed to induce tolerance in T cells compared to B cells. This suggests T-cell tolerance is more easily achievable.

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Maintenance of immunological tolerance

The persistence of an antigen is vital for maintaining tolerance. If the antigen disappears, tolerance can break down.

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Ignorance (in immunity)

A passive form of immunological tolerance where immune cells specific for self antigens are present but don't encounter them. Ignorance is bliss.

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Tolerance to soluble antigens

A state of tolerance to a variety of T-dependent and T-independent antigens. This shows that many factors determine if an antigen will trigger an immune response or tolerance.

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Tolerance to tissues and cells

The ability to create tolerance to tissue and cell antigens. This is especially important in situations like bone marrow transplantation.

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Study Notes

Immunological Tolerance

  • Immunological tolerance is the failure to mount an immune response to an antigen. This can be natural (self-tolerance) or induced.
  • Natural/Self-tolerance: The immune system doesn't attack the body's own proteins or antigens; crucial for preventing autoimmune diseases.
  • Induced tolerance: Tolerance to external antigens, achieved through several methods:
    • Treating allergic reactions (e.g., peanuts, insect stings, pollen).
    • Allowing transplanted organs to survive.
    • Preventing inflammation against harmless or beneficial gut bacteria.
  • Tolerance is an active, specific response to an epitope (part of an antigen recognized by antibodies).
  • T cell tolerance is more important than B cell tolerance because B cells need T cell help to produce antibodies to most antigens.

Types of Helper T Cells

  • Four types of helper T cells are identified:
    • Th1: Crucial for cell-mediated and antibody-mediated immunity, essential against intracellular pathogens (e.g., viruses, TB bacteria). Provides help to cytotoxic T lymphocytes.
    • Th2: Provides help to B cells, essential for IgE antibody production and some IgG subtypes. Crucial against extracellular pathogens.
    • Tfh (Follicular helper T cells): Provide help to B cells in lymphoid follicles, leading to antibody-secreting plasma cells. Most abundant helper T cell.
    • Th17: Protects surfaces against extracellular bacteria (e.g., skin, gut).

Central Tolerance

  • Central tolerance (also called negative selection) eliminates self-reactive T and B lymphocytes during development.
  • This process ensures the immune system doesn't attack self-antigens.
  • Lymphocyte maturation, including central tolerance, occurs in primary lymphoid organs (bone marrow, thymus).
  • B cells mature in the bone marrow, T cells in the thymus.

Mechanisms of Central Tolerance

  • B cell tolerance: Immature B cells that bind self-antigens undergo apoptosis (clonal deletion), receptor editing (modifying the receptor), or anergy (inactivation).

  • T cell tolerance:

    • Positive selection: T cells are tested for their ability to bind peptide-MHC complexes with appropriate affinity. Inability to bind means apoptosis. Binding results in survival and development as CD4+ or CD8+ T cells. This occurs in the thymic cortex.
    • Negative selection: T cells are checked for affinity to self-antigens. High affinity to self leads to apoptosis. This occurs in the thymic medulla. The thymus displays self-antigens for this process.

Peripheral Tolerance

  • A backup system to prevent autoimmunity in case of escaped self-reactive cells from central tolerance.
  • Mechanisms include anergy and regulatory T cells (Tregs).

Immune Tolerance - Mechanisms

  • Clonal deletion: Elimination of self-reactive T and B cells.
  • Clonal anergy: Inactivation of self-reactive T and B cells.
  • Peripheral suppression by T cells: Regulatory T cells suppress immune responses.

Tolerance Induction and Termination

  • Tolerogen: An antigen that induces tolerance.
  • Tolerance is specific and can be in B or T cells (or both). T-cell tolerance lasts longer than B-cell tolerance.
  • Tolerance to cells/tissues can be induced in neonatal animals or immunocompromised animals.
  • Tolerance can be broken naturally (autoimmune disease) or artificially (drug treatment, radiation).
  • Ignorance: A passive form of tolerance where the immune system doesn't "see" self-antigens, e.g. low concentrations or sequestered locations (eye, brain, testes).

Mechanisms of Tolerance Induction

  • Anti-idiotypic antibodies: Antibodies that bind to the receptors of other lymphocytes to regulate against the antigen response.
  • Suppressor cells (Regulatory T cells): Suppress immune responses through cytokine production, most importantly TGF-β and IL-10. CD4+ T cells that express high levels of IL-2rα chain (CD25) but not other activation markers.

Tolerance to Antigens

  • Tolerance to soluble antigens has been observed in different experimental models., showing various factors determine whether an immune response or tolerance to an antigen may occur.
  • Induction of tolerance in T cells is easier than in B cells. Persistence of the antigen is important for maintaining tolerance.

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Description

This quiz covers the concepts of immunological tolerance, including both natural and induced forms. It also explores the different types of helper T cells and their roles in the immune response. Dive into the mechanisms that prevent autoimmune diseases and facilitate organ transplants.

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