Lymphocyte and T Cell Development

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Questions and Answers

What represents the first step in lymphocyte development?

Differentiation of B and T cells into distinct subpopulations

Commitment of progenitor cells to either B lymphoid or T lymphoid lineage (correct)

Rearrangement of antigen receptor genes

Proliferation of immature committed cells

Which event in lymphocyte development is crucial for the preservation of functional cells?

Proliferation of progenitors

Rearrangement of Ig heavy chain gene

Selection events eliminating self-reactive cells (correct)

Differentiation into CD4+ and CD8+ T cells

What is the primary consequence of successful rearrangement of the TCR β chain gene?

Greatest proliferation of lymphocyte precursors (correct)

Differentiation into natural killer T cells

Apoptosis of non-functional lymphocyte precursors

Commitment to the B lymphoid lineage

What type of T cells results from the differentiation of T lymphocytes?

MAIT cells Signup and view all the answers

Which of the following pathways is crucial for generating a large pool of useful lymphocytes?

Proliferation of progenitors and immature committed cells Signup and view all the answers

What is the main function of positive selection during T cell maturation?

To preserve T cells that recognize self MHC molecules Signup and view all the answers

Negative selection in T cell development is crucial for maintaining what kind of tolerance?

Central tolerance by eliminating self-reactive T cells Signup and view all the answers

Which of the following describes the matching of T cell coreceptor to MHC molecule?

CD8 with class I MHC and CD4 with class II MHC Signup and view all the answers

What critical role does IL-7 play in T cell maturation?

It serves as a growth factor for lymphocytes Signup and view all the answers

What initiates the movement of T cells into and through the thymus?

Chemokines secreted by thymic stromal cells Signup and view all the answers

Which consequence results from a failure to rearrange the TCR β chain gene productively?

Apoptosis in the thymus Signup and view all the answers

What is the expected outcome for T cells that are positively selected in the thymus?

They will recognize foreign peptide antigens on self MHC Signup and view all the answers

What defines the αβ T cells after maturation?

They become restricted to either CD4+ class II MHC or CD8+ class I MHC Signup and view all the answers

What forms the pre-TCR complex in T cells?

TCR β chain, pre-Tα, CD3, and ζ proteins Signup and view all the answers

What is the primary role of positive selection in thymocytes?

To stimulate and differentiate thymocytes with low avidity for self peptide–MHC complexes Signup and view all the answers

Which signaling pathway significantly enhances T cell responses mediated by APCs?

Interaction of CD40L on T cells with CD40 on APCs Signup and view all the answers

What leads to the formation of a complete αβ TCR?

TCR α gene expression during the double-positive stage Signup and view all the answers

What type of T cells do double-positive cells primarily differentiate into after successful selection?

CD4+ or CD8+ T cells Signup and view all the answers

What role do costimulatory signals play in T cell activation?

They provide additional signals required beyond antigen recognition. Signup and view all the answers

Which therapeutic agent is used for blocking costimulation in conditions like rheumatoid arthritis?

CTLA-4-Ig Signup and view all the answers

In which area of the thymus does differentiation into single-positive T cells occur?

Medulla of the thymus Signup and view all the answers

What is the role of IL-7 in T cell development?

Enhances the proliferation of T cell progenitors Signup and view all the answers

Which transcription factors are crucial for B cell development?

EBF, E2A, and Pax-5 Signup and view all the answers

What epigenetic mechanism silences the expression of the CD4 gene in CD8+ T cells?

Methylation of DNA Signup and view all the answers

What is a consequence of deleting Dicer in the T lineage?

Preferential loss of regulatory T cells Signup and view all the answers

Which proteins are required for both B and T cell development?

Rag-1 and Rag-2 Signup and view all the answers

What is X-SCID attributed to?

Mutations in the IL-7 gene Signup and view all the answers

What is the first checkpoint during lymphocyte development?

Development of the pre-antigen receptor Signup and view all the answers

Which of the following statements about lymphocyte development is true?

Histone modifications can render genes either active or inactive. Signup and view all the answers

Study Notes

Lymphocyte Development

Lymphocyte development refers to the process by which progenitor cells in the thymus and bone marrow transform into mature lymphocytes that inhabit peripheral lymphoid tissues.
Key stages include progenitor cell commitment to B or T lymphoid lineages, proliferation of progenitors, antigen receptor gene rearrangement, selection of functional cells, and differentiation into distinct subpopulations.

T Lymphocyte Development

T lymphocyte development is guided by transcription factors, signaling proteins, and cytokines like IL-7.
Mutations in the IL-7 gene cause X-linked severe combined immunodeficiency disease (X-SCID), characterized by impaired T cell development.
Epigenetic mechanisms like DNA methylation, histone modifications, chromatin remodeling, and noncoding RNAs regulate lymphocyte development.

T Cell Receptor (TCR)

T cells express TCR proteins that recognize peptide antigens presented by MHC molecules.
The TCR is composed of variable and constant domains, with variable regions containing complementary determining regions (CDRs) responsible for antigen recognition.
The human TCR repertoire arises from rearrangements of TCRα and TCRβ genes.

T Lymphocyte Maturation in the Thymus

T lymphocytes mature in the thymus under the influence of thymic stromal cells, chemokines, and IL-7.
Pre-TCR complex formation triggers TCRα gene rearrangement and complete αβ TCR formation.
Selection processes in the thymus, including positive and negative selection, shape the T cell repertoire.

T Cell Subsets in the Thymus

Mature T cells with functional TCRs differentiate into CD4+ or CD8+ single-positive (SP) T cells in the thymus medulla.
Some double-positive cells develop into regulatory T cells (Treg CD4+).

T Cell Activation

T cell activation is initiated by antigen recognition and co-stimulation via interactions with antigen-presenting cells (APCs).
Co-stimulatory molecules like CD28 and CD40 contribute to T cell activation, enhancing proliferation and differentiation.

Costimulatory Pathways

Costimulatory pathways involve interactions between T cell surface molecules and APC surface molecules.
CD28 engagement on T cells triggers downstream signaling pathways that enhance T cell activation.
Other costimulatory molecules include CD40L, CTLA4, and ICOS.

Therapeutic Costimulatory Blockade

CTLA-4-Ig, a blocking antibody targeting CTLA4, is used to suppress immune responses in the treatment of rheumatoid arthritis and transplant rejection.

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Description

Explore the intricate processes involved in lymphocyte and T cell development. This quiz covers key stages such as progenitor cell commitment, receptor gene rearrangement, and the role of cytokines and transcription factors. Understand how these mechanisms contribute to a functional immune system.