Clonal Selection Theory Overview

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Questions and Answers

What does somatic recombination within antigen receptor gene loci primarily contribute to?

  • The deletion of self-reactive lymphocytes
  • Receptor repertoire diversity (correct)
  • The activation of effector cells
  • The physical structure of lymphocytes

Which of the following best describes the process of negative selection in B cell development?

  • Inactivation or deletion of lymphocytes with high affinity for self-antigens (correct)
  • Expansion of lymphocytes with diverse antigen specificity
  • Formation of memory B cells from activated lymphocytes
  • Activation of lymphocytes in response to foreign antigens

Which of the following statements is NOT one of the major tenets of clonal selection theory?

  • Antigen recognition leads to lymphocyte activation
  • Effector cells share the receptor specificity of their parent lymphocyte
  • Lymphocytes expand in response to their specific antigen
  • Each lymphocyte expresses multiple antigen-specific receptors (correct)

In the context of B cell receptors (BCR), what is the role of heavy and light chains?

<p>They determine the antigen specificity of the BCR (D)</p> Signup and view all the answers

What is the consequence of lymphocytes bearing receptors for self-molecules during the development process?

<p>They are inactivated or deleted (D)</p> Signup and view all the answers

What is the significance of having enough unique clones of lymphocytes?

<p>To leave no blind spots in immune response (A)</p> Signup and view all the answers

How does clonal selection theory explain the memory of the adaptive immune system?

<p>Activated lymphocytes produce diverse clones that all have the same specificity (C)</p> Signup and view all the answers

What distinguishes the clonal structure of lymphocytes during their development?

<p>Each lymphocyte expresses a unique antigen-specific receptor (A)</p> Signup and view all the answers

Which of the following processes occurs independently in each B cell and contributes to receptor diversity?

<p>Somatic rearrangement (C)</p> Signup and view all the answers

Which statement accurately describes B cell antigen receptor assembly?

<p>It involves the shuffling of gene segments from multiple loci (D)</p> Signup and view all the answers

What characterizes the configuration of the heavy (H) chain in B cell receptors?

<p>It consists of V, D, and J gene segments that are physically moved together. (C)</p> Signup and view all the answers

During B cell development, what stage contributes to negative selection?

<p>Immature B cell stage with strong antigen binding. (B)</p> Signup and view all the answers

What happens when a B cell binds a weak antigen post-bone marrow development?

<p>It becomes anergic and unresponsive to antigen. (B)</p> Signup and view all the answers

What is the role of T cells in isotype switching for B cells?

<p>They provide signals necessary for isotype switching. (D)</p> Signup and view all the answers

Where does somatic hypermutation primarily occur?

<p>In germinal centers of lymph nodes. (D)</p> Signup and view all the answers

What are complementarity determining regions (CDRs) significant for?

<p>Enhancing the binding ability of antibodies to antigens. (B)</p> Signup and view all the answers

Why is clonal selection important in B cell activation?

<p>It ensures that only B cells with high-affinity receptors are activated. (A)</p> Signup and view all the answers

What consequence does strong antigen binding have at the immature B cell stage?

<p>It results in apoptosis of the B cell. (A)</p> Signup and view all the answers

How does isotype switching affect antibodies?

<p>It changes the distribution and function of the antibodies while preserving specificity. (D)</p> Signup and view all the answers

What is the significance of the rearrangement of gene segments in B cell receptors?

<p>It establishes the clonal identity and specificity of antibodies. (D)</p> Signup and view all the answers

Flashcards

Clonal Selection Theory

A theory explaining adaptive immunity, stating that each lymphocyte has a unique antigen receptor, recognizing specific antigens. Activation leads to expansion of that specific lymphocyte clone.

Antigen-specific receptor

A protein on the surface of a lymphocyte that specifically recognizes and binds to a particular antigen.

Lymphocyte activation

The process in which a lymphocyte is stimulated to proliferate and differentiate into effector cells, upon binding with an antigen.

Self Molecules

Molecules produced within the body. Lymphocytes with receptors for self molecules are inactivated or deleted to prevent autoimmune reactions.

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B cell receptor (BCR)

A receptor on B cells that consists of heavy and light chains and recognizes antigens.

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B cell receptor gene loci

Locations on chromosomes that code for the BCR heavy and light chains. They are in germ-line arrangement.

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Somatic recombination

The process of shuffling gene segments within antigen receptor gene loci to create a diverse repertoire of antigen receptors, more than can be encoded in the genome.

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Antigen-dependent steps

Steps in B cell development triggered by an encounter with an antigen.

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Antigen-independent steps

Steps in B cell development that occur without direct interaction with an antigen.

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Receptor repertoire

The entire collection of diverse antigen receptors on lymphocytes.

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Germ-line gene configuration

Initial arrangement of genes for B cell receptors (BCRs) in the DNA, before rearrangement.

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BCR expression stages VDJ

B cell receptor expression starts with the arrangement of gene segments (V, D, J) for the heavy chain, then the light chain genes V and J rearrange and pair with a C gene segment.

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Clonal Selection Theory (Tenet 2)

B cell activation requires binding to an antigen (receptor binding is required).

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Clonal Selection Theory (Tenet 3)

B cell activation depends on the BCR binding to its specific antigen and triggering signaling pathways

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B cell negative selection

Process in bone marrow where strongly binding autoreactive B cells are deleted.

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Isotype switching

Changing the type of antibody produced by a B cell (e.g., from IgM to IgG).

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Somatic hypermutation

Process of mutations in the B cell receptor, making it bind antigen more strongly.

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Germinal centers

Specialized areas in lymph nodes where B-cell maturation (Isotype switching and somatic hypermutation) occurs.

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Antigen-dependent B cell development

B cell activation and maturation that occurs after leaving the bone marrow, requires antigen binding.

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T cell help

T cells helping B cells to mature, specifically during isotype switching and somatic hypermutation in germinal centers.

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Study Notes

Clonal Selection Theory

  • Each lymphocyte uniquely expresses a single antigen receptor with specific targeting. The complete repertoire of lymphocytes can respond to any antigen.
  • Lymphocyte activation requires binding to an antigen.
  • Activated lymphocytes' progeny (effector cells) express identical receptors as the parent cell.
  • Lymphocytes with receptors for self-antigens are either inactivated or eliminated.

Clonal Selection Theory: Tenets 1, 2, & 3

  • Tenet 1: Each lymphocyte is clonotypic, distinct from other cells except its immediate precursors or progeny. This is due to the antigen receptor and its genetic origin. Large diversity of lymphocytes is generated due to rearranged genes.

  • Tenet 2, 3: Receptor binding is crucial for lymphocyte activation. BCRs (B cell receptors) on the cell surface act with signalling molecules that recognize when an antigen is bound and activate the cell. This leads to antibody production and the cell's proliferation and differentiation. The B cell's clone and antibody's specificity are fixed by the initial receptor-generating rearrangement.

B Cell Receptor (BCR) Structure

  • BCR consists of heavy (H) and light (L) chains.
  • One H chain locus and two L chain loci (k and l).
  • The H chain has V, D, and J gene segments.
  • The L chain has V and J gene segments.
  • Only one L chain type (k or l) is expressed per cell.
  • H and L chains join to form the receptor. Heavy chains initially associate with the more 5' C-region genes (µ and δ).

B Cell Development

  • Antigen-independent: B cell development in the bone marrow, except for negative selection.
    • Autoreactive B cells with strong self-antigen binding undergo apoptosis deletion.
    • Weaker binding may result in anergy(non-responsiveness).
  • Antigen-dependent: B cell development in the periphery.
    • Antigen binding after leaving bone marrow can trigger IgM release.
    • Isotype switching and somatic hypermutation require T cell help. Occurs in germinal centers within lymph nodes.
  • Isotype switching: Altering antibody class (e.g., IgM to IgG) while maintaining the same antigen specificity. Crucial for different immune functions.
  • Somatic hypermutation: Mutations improve antigen binding within the antibody's variable regions, concentrated in hypervariable regions (CDRs). This occurs concurrently with isotype switching.
  • Germinal centers: Specialized areas in lymph nodes where B cell proliferation and maturation happen, along with isotype switching and somatic hypermutation, via T-cell interactions.

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