Immunology Chapter on Tolerance and T Cells

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Questions and Answers

What is the primary role of immunological tolerance in relation to self-antigens?

To increase inflammation in response to self-antigens.

To prevent the immune system from attacking harmless proteins. (correct)

To enhance immune responses against self-antigens.

To enable the immune system to recognize all antigens.

Which type of helper T cell is essential for the production of IgE antibodies?

Th1

Th17

Th2 (correct)

Tfh

What distinguishes induced immunological tolerance from natural tolerance?

Induced tolerance only affects T cells.

Induced tolerance occurs only in the presence of autoimmune diseases.

Induced tolerance involves manipulation of the immune system for external antigens. (correct)

Induced tolerance is a response to the body's own proteins.

Which type of T cells are primarily responsible for cell-mediated immunity?

Th1 cells Signup and view all the answers

What is the role of Tfh (follicular helper T) cells?

Facilitating the development of B cells into antibody-secreting plasma cells. Signup and view all the answers

What could be a consequence of the immune system mistakenly responding to 'self' antigens?

Autoimmune diseases may develop. Signup and view all the answers

Why is tolerating T cells considered more crucial than tolerating B cells?

B cells require help from T cells to produce antibodies. Signup and view all the answers

Which type of helper T cells is primarily involved in protecting surfaces against extracellular bacteria?

Th17 Signup and view all the answers

What is one of the reasons for ignorance in the immune response?

The antigen may appear in a very low concentration. Signup and view all the answers

What happens during clonal deletion in the immune system?

Functionally immature cells undergo programmed cell death. Signup and view all the answers

Which mechanism helps prevent auto-reactive T cells from responding to self-antigens?

Clonal anergy. Signup and view all the answers

What role do anti-idiotype antibodies have in immune response?

They inhibit immune responses to specific antigens. Signup and view all the answers

What is a consequence of receptor editing in B cells?

B cells change their antigen specificity. Signup and view all the answers

Which cytokines are primarily produced by regulatory T cells to suppress immune responses?

IL-10 and TGF-β. Signup and view all the answers

What can terminate experimentally induced tolerance?

Prolonged absence of the tolerogen. Signup and view all the answers

What is a distinguishing feature of regulatory T cells?

High levels of IL-2r α chain (CD25). Signup and view all the answers

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

To eliminate developing lymphocytes that are reactive to self Signup and view all the answers

Which of the following cells undergoes maturation in the thymus?

T cells Signup and view all the answers

What happens to T cells that do not bind to MHC complexes during positive selection?

They undergo apoptosis Signup and view all the answers

What mechanism is NOT associated with central tolerance?

Peripheral suppression by T cells Signup and view all the answers

What is clonal deletion in the context of B cell tolerance?

Apoptosis of B cells that recognize self antigens Signup and view all the answers

Which process allows B cells that bind to self peptides to develop a new receptor?

Receptor editing Signup and view all the answers

During which selection process are T cells tested for their affinity to self antigens?

Negative selection Signup and view all the answers

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

They express self tissue antigens on thymic epithelial cells Signup and view all the answers

How does peripheral tolerance function as a secondary mechanism?

It controls auto-reactivity after cells exit primary lymphoid organs Signup and view all the answers

Which term describes an antigen that induces a state of tolerance?

Tolerogen Signup and view all the answers

Compared to B cell tolerance, how is T cell tolerance characterized?

It is easier to induce and requires smaller amounts of tolerogen Signup and view all the answers

What can cause the breakdown of tolerance in the immune system?

Lack of antigen persistence Signup and view all the answers

What characterizes the concept of 'ignorance' in immunological tolerance?

Presence of self-reactive T and B cells unaware of their auto-antigen Signup and view all the answers

Study Notes

Immunological Tolerance

Immunological tolerance is the failure to mount an immune response to an antigen.
It can be natural (self-tolerance) or induced.
Natural tolerance prevents the immune system from attacking the body's own proteins—failure to do so results in autoimmune diseases.
Induced tolerance is directed against external antigens. Examples include:
- Preventing allergic reactions (e.g., to peanuts, insect stings, pollen).
- Enabling transplanted organs to survive.
- Preventing inflammation against harmless/beneficial gut bacteria.
Tolerance is an active, specific response to an epitope (antigen part), similar to an immune response.
B cells and T cells can be tolerant, but T cell tolerance is more critical because B cells need T cell help to make antibodies.

Types of Helper T Cells

Th1: Participate in both cell-mediated and antibody-mediated immunity. Crucial for controlling intracellular pathogens (e.g., viruses, TB bacteria). Assists cytotoxic T cells (potent weapons against intracellular pathogens) via cytokines.
Th2: Crucial for B cell help and IgE antibody production; also assists in some IgG production. Needed to control extracellular pathogens.
Tfh (Follicular Helper T cells): Provide help to B cells to become antibody-secreting plasma cells in lymphoid follicles. The most abundant helper T cells; specialized in B cell support.
Th17: Protect surfaces (e.g., skin, gut) from extracellular bacteria.

Central Tolerance

Also known as negative selection.
Eliminates developing T and B lymphocytes that react to self-antigens.
Ensures immune system does not attack the body's own peptides.
Occurs in primary lymphoid organs (thymus and bone marrow).
B cell maturation in bone marrow and T cell in thymus.

B Cell Tolerance

Immature B cells in bone marrow undergo negative selection if they bind to self-peptides.
Proper functioning BCRs recognize non-self antigens/pathogen-associated molecular patterns.
Outcomes of BCR auto-reactivity include:
- Apoptosis (clonal deletion)
- Receptor editing (change to a non-self-reactive BCR)
- Induction of anergy (non-reactivity)

T Cell Tolerance

Occurs in the thymus.
Involves both positive and negative selection.
T cell receptors must recognize self MHC molecules with bound non-self peptides.

Steps of T Cell Tolerance

Positive selection: T cells tested for ability to bind peptide-MHC complexes with affinity. Cells incapable of binding MHC I or II die. Selected cells survive and are either CD8+ (MHC I) or CD4+ (MHC II). Positive selection occurs in the thymic cortex.
Negative selection: T cells tested for affinity to self-peptides; if they bind, they undergo apoptosis. Thymic epithelial cells display self-antigens. Negative selection occurs in the cortico-medullary junction and thymic medulla.
Selected T cells (not self-reactive) migrate to secondary lymphoid organs as mature naïve T cells.

Peripheral Tolerance

A backup mechanism to control auto-reactivity of cells escaping central tolerance.
Occurs after cells leave primary lymphoid organs.
Mechanisms include: T-cell anergy, regulatory T cells, and clonal deletion
Mechanisms include clonal deletion, clonal anergy, and peripheral suppression by T cells.

Tolerance cont....

Tolerogen: antigen that induces tolerance.
Tolerance to tissues and cells can be experimentally induced by injecting hemopoietic stem cells or grafting bone marrow/thymus during early life. Chimeras are produced.
Tolerance to soluble antigens can be experimentally induced.
Induction of tolerance to T cells is easier than B cells.
Antigen persistence is required to maintain tolerance.
Tolerance can be broken naturally or artificially.

Ignorance

Passive form of immunological tolerance.
Auto-reactive T and B cells may exist but are unaware of their auto-antigens due to low antigen concentration or sequestration in privileged sites.
Failure to trigger a response because receptors aren't sufficiently occupied by the antigen.

Mechanisms of Tolerance Induction

Anti-idiotypic antibodies: Experimentally produced antibodies that can inhibit immune responses to specific antigens.
Suppressor cells (Regulatory T cells): CD4+ T lymphocytes expressing high levels of CD25.
Generated through self-antigen recognition in thymus or periphery. Produce TGF-β and IL-10 to suppress immune responses.

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Description

Explore the concept of immunological tolerance, including its natural and induced forms, and the crucial role of T cells in immune responses. This quiz covers the mechanisms that prevent the immune system from attacking self-antigens and the importance of tolerance in preventing autoimmune diseases and enabling organ transplants.