T Cell Development and Activation

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Questions and Answers

What is the primary location where T cell precursors complete their maturation?

  • Spleen
  • Bone marrow
  • Lymph nodes
  • Thymus (correct)

Which process allows T cells to recognize self-MHC during their development?

  • Negative selection
  • Positive selection (correct)
  • T cell activation
  • Co-receptor selection

What happens to thymocytes that do not recognize an MHC molecule within 3-4 days of initial expression?

  • They become activated
  • They die (correct)
  • They migrate to the spleen
  • They undergo positive selection

Which cells mediate positive selection in the thymus?

<p>Cortical epithelial cells (B)</p> Signup and view all the answers

What is the outcome for CD4LOW CD8HIGH thymocytes that recognize MHC class I molecules?

<p>They survive (B)</p> Signup and view all the answers

What is a characteristic of thymocytes that survive both positive and negative selection?

<p>They are self-tolerant naive T cells (C)</p> Signup and view all the answers

In which part of the thymus does negative selection primarily take place?

<p>Both cortex and medulla (C)</p> Signup and view all the answers

Which cell types play a role in negative selection of thymocytes?

<p>Cortical epithelial cells and dendritic cells (A)</p> Signup and view all the answers

What primarily influences the survival or death of thymocytes during selection?

<p>Binding affinity to MHC-peptide complexes (B)</p> Signup and view all the answers

What is the role of co-receptor downregulation during T cell development?

<p>To enable selection of specific T cell lineages (A)</p> Signup and view all the answers

What role does IL-2 play in T cell activation?

<p>It facilitates the proliferation and differentiation of T cells. (B)</p> Signup and view all the answers

Which process ensures that T cells recognize self-MHC molecules during their development?

<p>Positive selection allows only T cells that bind to self-MHC. (D)</p> Signup and view all the answers

What determines the type of effector T cell that a T cell will become?

<p>The presence of specific cytokines expressed by APCs. (C)</p> Signup and view all the answers

During T cell activation, what is the significance of the co-stimulatory signal B7:CD28?

<p>It enhances T cell survival and proliferation. (D)</p> Signup and view all the answers

What is the primary role of T cells in immune defense?

<p>Attacking intracellular pathogens and cancerous cells. (A)</p> Signup and view all the answers

What is the significance of cell adhesion molecules (CAMs) in T cell activation?

<p>They allow for stable interactions between T cells and APCs. (A)</p> Signup and view all the answers

What characterizes the transition of naive T cells to effector T cells?

<p>Clonal expansion triggered by antigen and co-stimulation. (D)</p> Signup and view all the answers

What is the first step in T cell activation?

<p>Recognition of antigen presented by MHC molecules. (A)</p> Signup and view all the answers

Which T cell subset is primarily associated with helping other immune cells?

<p>CD4+ helper T cells. (D)</p> Signup and view all the answers

What physiological process occurs during T cell activation following antigen recognition?

<p>Entry into the cell cycle and clonal expansion. (B)</p> Signup and view all the answers

Flashcards

Positive Selection

The stage of T cell development where immature T cells learn to recognize and bind to self-MHC molecules, a crucial step for immune system function.

Negative Selection

A process in T cell development where immature T cells that bind too strongly to self-MHC-peptide complexes are eliminated, preventing autoimmune reactions.

T Cell Activation

The process by which T cells become mature and capable of recognizing and responding to specific antigens presented by antigen-presenting cells (APCs).

Antigen-Presenting Cells (APCs)

Special cells like dendritic cells (DCs) that capture and display antigens to T cells, initiating the immune response.

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MHC Class I

A major histocompatibility complex (MHC) protein that is expressed on all nucleated cells in the body; it presents intracellular antigens to CD8+ T cells.

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MHC Class II

A major histocompatibility complex (MHC) protein that is expressed on antigen-presenting cells; it presents extracellular antigens to CD4+ T cells.

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CD8+ T Cell (Cytotoxic T Cell)

A type of T cell that recognizes MHC Class I molecules and is responsible for killing infected cells.

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CD4+ T Cell (Helper T Cell)

A type of T cell that recognizes MHC Class II molecules and helps other immune cells fight infections by producing cytokines.

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Cytokines

Proteins secreted by T cells that influence other immune cells, promoting inflammation, activating other immune cells, or suppressing the immune response.

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Naive T Cell

A type of T cell that has not yet encountered its specific antigen and therefore is not activated; they are ready to mount an immune response when needed.

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T cell monitoring of APCs

T cells scan the MHC:peptide complexes on Antigen Presenting Cells (APCs) to identify foreign antigens.

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T cell development

A process where T cells develop from hematopoietic stem cells in the bone marrow into mature T cells in the thymus.

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T cell activation & differentiation

Antigen recognition initiates T cell activation, leading to differentiation into various effector T cell subsets.

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Positive and Negative selection of T cells

A vital process that ensures T cells only recognize and attack foreign antigens while avoiding self-antigens.

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B7:CD28 co-stimulation

A co-stimulatory signal crucial for T cell activation, delivered by interaction between B7 protein on APCs and CD28 protein on T cells.

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T cell clonal expansion

The phase following antigen recognition and co-stimulation where T cells enter the cell cycle and proliferate.

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IL-2's role in T cell activation

A key cytokine involved in T cell proliferation and differentiation into effector cells.

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Effect of cytokines on T cell differentiation

The type of effector T cell a naive T cell becomes is determined by the cytokines expressed by the APC during activation.

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T cell mediated immunity

A type of immune response involving T cells, essential for protecting against intracellular pathogens, cancer cells, and infected cells.

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T cell circulation & antigen seeking

T cells move between blood and lymphatic vessels, constantly searching for antigen presenting cells (APCs) displaying foreign antigens.

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Study Notes

T Cell Development and Activation

  • T cells develop from hematopoietic stem cells in the bone marrow, but complete maturation in the thymus.
  • The thymus is divided into lobules with a cortex and medulla.
  • Development stages are identified by the presence/absence of cell-surface markers (TCR, CD3, CD4, CD8).
  • T-cell precursors proliferate extensively in the thymus, and most die there.
  • T cells differentiate into two lineages: γ:δ and α:β.
  • α:β T cells further distinguish into CD4+ and CD8+ T cells.
  • T cells that recognize self-MHC (positive selection) and are self-tolerant (negative selection) are generated.

Learning Objectives

  • Describe the stages of T cell development from hematopoietic stem cells in the bone marrow to mature T cells.
  • Recognize positive and negative selection in T cell development.
  • Describe the process of T cell activation.
  • Understand T cell-mediated immune responses.

Positive Selection

  • Occurs in the thymic cortex.
  • Mediated by thymic cortical epithelial cells expressing MHC class I and II proteins.
  • Thymocytes that do not recognize MHC molecules within 3-4 days of α:β expression die.
  • Successful recognition by cortical epithelial cells results in a survival signal.

Co-receptor Selection

  • Recognition of an MHC molecule by one co-receptor results in downregulation of the other co-receptor gene.
  • CD4lowCD8high cells survive if they recognize MHC class I molecules.
  • CD4highCD8low cells survive if they recognize MHC class II molecules.
  • Co-receptor recognition by epithelial cells triggers a maturation signal.

Negative Selection

  • Occurs in the thymic cortex and medulla.
  • Mediated by cortical epithelial cells, macrophages, and dendritic cells.
  • Thymocytes that strongly recognize self-peptide:MHC complexes die.
  • Different binding affinities to MHC-peptide drive survival or death (positive/negative selection).
  • Self-peptides are derived from thymic and ubiquitous blood proteins.
  • T cells that successfully complete positive, co-receptor, and negative selection are single positive, self-tolerant, naïve T cells.

T Cell Activation

  • Antigen recognition occurs on antigen-presenting cells (APCs) by MHC-peptide complexes.
  • Co-stimulatory signals are delivered (e.g., B7:CD28).
  • T cells enter the cell cycle (G1) for proliferation, known as clonal expansion.
  • Interleukin-2 (IL-2) mediates proliferation and differentiation into effector cells.
  • Cytokines expressed by APCs determine the effector T cell type.

T Cell-Mediated Immunity

  • Naive T cells circulate between blood and lymphoid tissues.
  • Activation occurs via antigen co-stimulation and recognition of MHC-peptide complexes on APCs.
  • Cell adhesion molecules (CAMs) mediate the process.
  • T cells monitor MHC-peptide complexes within lymphoid tissue.

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