Immunology Lecture 6 Flashcards

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Questions and Answers

Which of the following ways do CSR and V(D)J recombination differ? (Select all that apply)

VDJ is regulated; CSR is random.

VDJ occurs in the bone marrow; CSR occurs in the germinal center. (correct)

VDJ yields antibodies with different specificity; CSR yields antibodies with the same specificity. (correct)

VDJ requires RAG-1 and 2; CSR requires AID and UNG. (correct)

What are the substrates for CSR?

Constant region genes in heavy chain.

How does AID work?

Converts C to U by deamination reaction.

What regulates specific class switch events?

By cytokines and CD40L. Signup and view all the answers

Why are antibodies widely used?

They can be secreted and act at distance, and have variable effector functions. Signup and view all the answers

What is Ig Class Switch Recombination (CSR)?

It changes out heavy chain constant regions to replace IgM/IgD with other isotypes. Signup and view all the answers

What is required for a B cell to switch isotopes?

CD40L and an instructive cytokine signal. Signup and view all the answers

Where do isotype switching and affinity maturation occur?

Germinal centers. Signup and view all the answers

What regions determine antibody isotype?

Heavy chain constant regions. Signup and view all the answers

What does class switching affect regarding antibodies?

Only affects effector function. Signup and view all the answers

What are the roles of AID and UNG in class switching?

AID converts C to U and UNG removes U. Signup and view all the answers

Are T cells important in class switching?

Yes, they activate B cells. Signup and view all the answers

How is diversity established in BCR and TCR?

Through isotype switching and affinity maturation. Signup and view all the answers

What happens if there is a mutation in AID or UNG?

Loss of class switch recombination and somatic hypermutation. Signup and view all the answers

Why is class switching important?

It changes the effector function of the antibody. Signup and view all the answers

What defines affinity maturation?

Competition and clonal selection in the germinal center. Signup and view all the answers

What occurs during somatic hypermutation?

Diversification of the variable regions by point mutations. Signup and view all the answers

What mechanisms regulate somatic hypermutation?

Transcription and AID. Signup and view all the answers

What happens to B cells after SMH and affinity maturation?

They differentiate into plasma or memory B cells. Signup and view all the answers

What are the important steps in memory B cell development?

Isotype switching, clonal expansion, SMH, and affinity maturation. Signup and view all the answers

How do different heavy chain constant regions affect antibodies?

They encode different classes of antibodies. Signup and view all the answers

What generates diversity in the Ig repertoire?

Combinational diversity, junctional diversity, somatic hypermutation, and isotype switching. Signup and view all the answers

What is combinational diversity?

Somatic recombination of VDJ and VJ gene segments. Signup and view all the answers

What is junctional diversity?

Addition of random nucleotides. Signup and view all the answers

What are the effector functions of antibodies?

Neutralization, opsonization, and complement activation. Signup and view all the answers

What are the major enzymes involved in class switch recombination?

AID, UNG, and APE. Signup and view all the answers

RAG 1/2 are required for isotype switching.

False Signup and view all the answers

When and where does class switching recombination occur?

After stimulation of mature B cells in the germinal center. Signup and view all the answers

What distinguishes VDJ recombination from CSR?

VDJ is random, while CSR is instructed. Signup and view all the answers

What is the difference between CSR and SHM?

CSR involves heavy chain constant regions; SHM involves variable regions. Signup and view all the answers

How do BCR and TCR differ?

BCR recognizes free-floating antigens; TCR recognizes MHC-bound antigens. Signup and view all the answers

Study Notes

Class Switch Recombination (CSR) vs V(D)J Recombination

CSR and V(D)J recombination involve different processes and signal pathways.
V(D)J recombination occurs randomly in the bone marrow and involves both heavy and light chains, while CSR is regulated and occurs in germinal centers, affecting only heavy chains.
V(D)J produces antibodies with different specificities, while CSR changes effector functions without altering specificity.
V(D)J recombination requires RAG-1 and RAG-2 proteins, while CSR relies on AID and UNG enzymes.

Substrates and Key Factors

CSR targets constant region genes in the heavy chain, performed in the germinal center with AID, UNG, and APE involved.
Somatic Hypermutation (SHM) affects the variable regions of both heavy and light chains, also occurring in the germinal center.

Mechanism of AID

AID converts cytosine (C) to uracil (U) through deamination, operating at variable and switch regions during CSR.

Regulation of Class Switch Events

Class switch events are regulated by cytokines and the CD40L:CD40 interaction.
IL-4 induces IgG1 and IgE, IL-5 prompts IgA augmentation, IFN-y induces IgG3 and IgG2a, TGF-β leads to IgG2b, and IL-21 promotes IgG1, IgG3, and IgA.

Antibody Functions in Research and Therapy

Antibodies are versatile lab reagents, diagnostic tools, and therapeutics due to their ability to act distally, recognize antigens with high specificity, and have variable effector functions.

Overview of Class Switch Recombination

CSR replaces IgM/IgD with other isotypes, maintaining the antigen-binding site but altering effector properties.
Only B cells undergo CSR, which is specific to regions.

Determinants of B Cell Isotope Switching

Upon leaving the bone marrow, B cells express IgM and IgD and can switch to IgG, IgA, or IgE during immune responses.
Whereas V(D)J recombination is random, CSR is an instructive process initiated by cytokine signals.

Isotype Switching and Affinity Maturation Location

Both processes occur in germinal centers after stimulation of mature B cells.

Antibody Isotype Determination

The heavy chain constant regions dictate antibody isotype.
Immature B cells express IgM and IgD, while mature B cells express IgG, IgA, or IgE.

Effects of Class Switching on Antibody Function

Class switching affects the effector function of antibodies without altering the binding affinity for specific antigens, as the V(D)J sequence remains unchanged.

Enzymatic Roles in Class Switching

AID alters single-stranded DNA, converting C to U; UNG removes U, and APE generates nicks, facilitating double-strand breaks at switch regions.

T Cells' Role in Class Switching

Activation of B cells by protein antigens and helper T cells induces AID expression and migration into germinal centers.

Comparison of TCR and BCR

TCR acts only as an antigen-specific receptor, while BCR functions as both a receptor and an effector molecule, with diversity achieved through isotype switching and affinity maturation.

Implications of AID or UNG Mutations

Mutations in AID or UNG disrupt class switch recombination and somatic hypermutation, impacting B cell receptor diversity.

Importance of Class Switching

Class switching is crucial as it alters antibody effector functions, without improving affinity toward the antigen.

Affinity Maturation Process

Occurs through clonal selection of high-affinity B cells in germinal centers, with competition for antigens presented by follicular dendritic cells.

Somatic Hypermutation (SHM)

SHM diversifies variable regions through point mutations, enhancing antigen binding, and is restricted to B cells in germinal centers.

Outcomes of Somatic Hypermutation

Possible outcomes include increased affinity, decreased affinity, unchanged affinity, loss of specificity, or a change in specificity due to mutations.

Dangers of SHM

Potential for "horror autotoxicus," where SHM may lead to self-reactive B cells, but checkpoints exist to prevent this.

Fate of B Cells Post-SMH

B cells that pass through SMH and affinity maturation differentiate into plasma cells or memory B cells, with plasma cells secreting high-affinity antibodies.

Key Steps in Memory B Cell Development

Involvement of isotype switching, clonal expansion, somatic hypermutation, and affinity maturation to ensure long-lasting immune responses.

Diversity of Immunoglobulin Repertoire

Generated through combinational diversity, junctional diversity, somatic hypermutation, and isotype switching.

Functions of Antibodies

Neutralization of pathogens, opsonization for phagocytosis, and complement activation enhance immune responses.

Major Enzymes in Class Switch Recombination

AID facilitates cytidine deamination, UNG creates basic sites, and APEI generates nicks necessary for recombination.

Class Switching Requirements

RAG-1 and RAG-2 are not required for isotype switching; this process relies on different enzymatic mechanisms.

Timing and Location of CSR vs. SHM

CSR occurs in germinal centers post-B cell stimulation, while SHM occurs during antibody responses, also within germinal centers.

Distinctions Between VDJ and CSR

VDJ is random, affects both T and B cells in the bone marrow, while CSR is instructed, only impacting heavy chains in B cells.

Differences Between CSR and SHM

CSR modifies heavy chain constant regions, involving different enzymes, while SHM further diversifies variable regions through point mutations.

BCR vs TCR Characteristics

BCR can recognize both free and MHC-bound antigens, undergoes CSR and SHM, while TCR only recognizes MHC-bound antigens and does not undergo CSR or SHM.

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Test your knowledge on the differences between Class Switch Recombination (CSR) and V(D)J recombination in immunology. This quiz will help you understand key concepts and mechanisms involved in antibody function and B-cell development. Perfect for students eager to master the intricacies of immunological processes.