Immunology TCR Structure and Development

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Questions and Answers

What are the key domains present in the TCR alpha chain?

Vβ, Cβ, Dβ

Vγ, Jγ, Cγ

Vδ, Jδ, Cδ

Vα, Jα, Cα (correct)

Which enzymes are involved in the recombination of TCR gene segments?

RAG-1, PCR, TdT

RAG-2, RNA polymerase, TdT

CD4, CD8, TdT

RAG-1, RAG-2, TdT (correct)

What happens to the majority of immature T cells in the thymus?

They migrate back to the bone marrow.

They are modified to become memory T cells.

They die by apoptosis and are eliminated. (correct)

They undergo rapid cell division.

During which phase do T cell precursors express neither CD4 nor CD8 receptors?

Double negative phase Signup and view all the answers

What is a key characteristic of gamma-delta T cells?

They can enter circulation and play roles in both innate and adaptive immunity. Signup and view all the answers

What forms after the successful association of the beta chain with a pre-TCR alpha chain?

Pre-TCR complex Signup and view all the answers

What is the role of macrophages during T cell development in the thymus?

They phagocytose the cellular debris from apoptotic cells. Signup and view all the answers

What is the main reason the T cell development process is considered wasteful?

A significant percentage of immature T cells undergo apoptosis. Signup and view all the answers

What percentage of double-positive thymocytes graduate to become naïve T-cells?

2% Signup and view all the answers

Where do single positive T-cells express homing molecules for trafficking?

High endothelial venules (HEVs) Signup and view all the answers

Which of the following locations is specifically mentioned as a site for B-cell maturation in certain species?

Bursa of Fabricius Signup and view all the answers

Which component is NOT involved in the B Cell Receptor structure?

TCR Signup and view all the answers

What allows naïve T-cells to migrate to peripheral sites after recognizing their antigen?

Acquisition of specific receptors Signup and view all the answers

What is one major characteristic of B-cell maturation compared to T-cell development?

It is less well characterized overall. Signup and view all the answers

What is the primary source of B lymphocytes?

Bone marrow stem cells Signup and view all the answers

Which organ is specifically associated with the final stages of B-cell maturation in ruminants?

Ileal Peyer’s patch Signup and view all the answers

What is the outcome for double positive cells during positive selection in the thymus?

Only approximately 5% of double positive cells will survive. Signup and view all the answers

What must an immature T cell do to successfully pass positive selection?

Ensure moderate-affinity interaction with the MHC-peptide complex. Signup and view all the answers

During negative selection, what type of cells do immature T cells encounter?

Thymic dendritic cells expressing self-peptides in the context of MHC. Signup and view all the answers

What is the primary goal of negative selection in the thymus?

To eliminate T cells that recognize auto-antigens with high affinity. Signup and view all the answers

What happens to T cells that produce a TCR with no or low affinity for peptide-MHC during positive selection?

They die by neglect. Signup and view all the answers

Which of the following is important for the positive selection of T cells?

Presence of a moderate-affinity connection between TCR and peptide-MHC complexes. Signup and view all the answers

Which cells display a wide range of normal tissue antigens during T cell development?

Thymic epithelial cells. Signup and view all the answers

What role does the AIRE gene play in T cell development?

It helps express peptides from non-thymic tissues. Signup and view all the answers

Which enzyme complex is responsible for the recombination of V, D, and J regions to form B cell receptors?

RAG-1 and RAG-2 complex Signup and view all the answers

What initiates the rearrangement process of B cell receptors?

Heavy chain recombination Signup and view all the answers

What process allows B cells to express different constant regions such as IgG, IgE, and IgA?

Class switching Signup and view all the answers

Which type of chains are involved in the light chain genes of immunoglobulins?

Kappa and Lambda chains Signup and view all the answers

During which stage do B cells first express the μ heavy chain?

Pre-B cell stage Signup and view all the answers

What occurs during alternative junctional recombination in B cells?

Recombination of V-J or V-D-J segments Signup and view all the answers

What type of genetic change does somatic mutation describe?

Point mutations in gene sequences Signup and view all the answers

Which immunoglobulin heavy chain is expressed first according to the gene arrangement?

IgM Signup and view all the answers

What occurs to BCRs that bind to self-antigens during B cell development?

They undergo deletion through apoptosis. Signup and view all the answers

What is the process called when a B cell undergoes further gene rearrangements to express an edited BCR?

Receptor editing Signup and view all the answers

Which type of antibodies are lacking in animals affected by SCID?

IgG and IgA Signup and view all the answers

What treatment approach has been researched for SCID in dogs?

Gene therapy Signup and view all the answers

Which breed of dog is NOT mentioned as being affected by SCID?

Labrador retriever Signup and view all the answers

What does the co-expression of IgM and IgD on naïve B lymphocytes signify?

The transition to active B cell participation. Signup and view all the answers

What mutation is associated with SCID in Jack Russell terriers?

Mutation in the DNA protein kinase gene. Signup and view all the answers

What is a clinical consequence of SCID in affected animals?

Lymphopenia. Signup and view all the answers

Study Notes

### TCR Structure

T cell receptors (TCR) have alpha and beta chains.
Alpha chain has a variable domain (Vα), a joining region (Jα), and a constant domain (Cα).
Beta chain has Vβ, Cβ, Jβ, and diversity region (Dβ).
There are multiple genes encoding Vα, Jα, Vβ, and Jβ regions.
There's a single constant region gene for the Alpha chain (Cα).
TCR α, β, γ, and δ chains are assembled by mixing and matching gene segments.
Gamma (γ) and delta (δ) chains may form γδ T cells involved in innate and adaptive immunity.

T Cell Development

T cell development occurs in the thymus.
Thymocyte progenitors originate in bone marrow and migrate to the thymus.
Double-negative phase: Progenitors initially lack CD4 and CD8 receptors.
Recombination: RAG-1, RAG-2, and TdT facilitate recombination of TCR gene segments, forming V(D)J regions.
Pre-TCR formed by β chain and pre-Tα chain.
Double-positive phase: Functional pre-TCR leads to cell proliferation and CD4/CD8 co-expression.
Alpha chain rearrangement: α chain complexes with β chain and CD3 to form the complete TCR.

T Cell Selection

Positive selection occurs in the thymus cortex.
Only 5% of double-positive cells survive.
Cells acquire CD4 or CD8 based on their specificity for MHC I or II, respectively.
TCR must interact with MHC-peptide complex, but with moderate affinity.
Cells with no or low affinity die by neglect.
Negative selection occurs in the thymus medulla.
Tests whether TCRs recognize self-antigens with high affinity.
Cells with high affinity for self-antigens undergo apoptosis.
Only 2% of double-positive thymocytes become single-positive (CD4 or CD8) naïve T cells.

Naïve T Cells

Naïve T cells leave the thymus and circulate.
They express homing molecules to traffic through lymph nodes via high endothelial venules (HEVs).
Activation occurs upon antigen recognition.

B Cell Development

B cells arise from bone marrow stem cells.
Maturation involves interactions with stromal cells.
Maturation occurs in bone marrow and possibly extramedullary locations like ileal Peyer's patches (ruminants) or bursa of Fabricius (birds).
B cell receptor (BCR) includes Igα and Igβ signal transducing molecules.
BCR diversity achieved by recombining variable (V), diversity (D), and joining (J) regions.

BCR Diversity

V(D)J recombinase complex, including RAG-1 and RAG-2, facilitates recombination.
Light chains can be either kappa (Cκ) or lambda (Cλ), involving V and J segments (no D region).
Heavy chain rearrangement first, followed by light chain rearrangement if successful.
Heavy chain constant region genes arranged in the order Cμ, Cδ, Cγ, Cε, and Cα, with IgM being the first expressed.

B Cell Activation and Class Switching

Activated mature B cells undergo class switching, expressing different constant regions (IgM to IgG, IgE, or IgA).
Junctional alternatives and somatic mutations further increase BCR diversity.

B Cell Maturation Stages

Pre-B cells produce μ heavy chain in the cytoplasm.
Immature B cells display complete IgM monomers on their surface.
Negative selection eliminates self-reactive BCRs by apoptosis or receptor editing.
Naïve B cells co-express surface IgM and IgD, joining the recirculating B-cell pool.

Severe Combined Immunodeficiency (SCID)

SCID affects dogs and horses, as well as humans.
Canine SCID involves mutations in the DNA protein kinase gene, affecting VDJ recombination in TCR and BCR formation.
Results in lack of adaptive immunity, bacterial/viral infections, lymphopenia, and hypoplasia of lymphoid tissue.
SCID is treated by bone marrow transplantation, stem cell transplantation, or gene therapy.
Arab horses also exhibit SCID due to a deletion in the DNA-dependent protein kinase involved in VDJ recombination.

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Description

Explore the structure and development of T cell receptors (TCR) in this detailed quiz. Understand the components of alpha and beta chains, gene segment recombination, and the stages of T cell development occurring in the thymus. Test your knowledge on the intricate processes that contribute to adaptive immunity.