T Cell Development Notes

T Cell Development Overview

• Production Location: T cells are produced in red bone marrow and then migrate to the thymus gland for maturation.

Primary Lymphoid Organs

• Definition: Primary lymphoid organs are where lymphocytes mature. For T cells, it is the thymus gland; for B cells, it is the red bone marrow.
• Thymus Gland:
  • Location: Overlies the heart in the mediastinum cavity.
  • Function: Essential for T cell maturation during infancy to early adolescence; atrophies post-adolescence, becoming fibrous and nonfunctional.

Chemotaxis and Migration to Thymus

• Chemotactic Agents: The thymus secretes several factors that guide immature T cells to itself, including:
  • Thymosin
  • Thymotaxin
  • Thymic Factors
• These agents initiate chemotaxis, attracting T cell precursors to the thymus gland.

Maturation Process in Thymus

1. Initial Stages:

   • T cell precursors receive signals from thymic cells (e.g., thymosin) which activate genes responsible for T cell receptor (TCR) production.
   • Specific enzymes produced (RAG-1 and RAG-2) shuffle DNA to create diverse TCRs that can recognize various antigens.

2. Receptor Development:

   • Activation leads to the production of cluster differentiation proteins (CD4 and CD8), marking T cell types.
   • This differentiation is influenced by their interactions with thymic cells which present MHC (Major Histocompatibility Complex) class I and II molecules.

Positive Selection

• Definition: A process where T cells that successfully recognize MHC molecules receive survival signals.
• Mechanism:
  • T cells express CD4 or CD8 and must bind adequately to MHC I or MHC II complexes on thymic cells.
  • T cells that do not recognize these markers undergo apoptosis (programmed cell death).

Negative Selection

• Definition: A process to eliminate T cells that react strongly to self-antigens (body's own peptides).
• Mechanism:
  • T cells that bind too well to self-peptides undergo apoptosis to prevent autoimmunity.
  • Thymic cells secrete factors (like phos) that trigger apoptosis in case of inappropriate binding.

Final Differentiation of T Cells

• Based on interactions with MHC molecules:
  • CD4 Positive T Cells: Interact with MHC II → T helper cells (provides help to other immune cells).
  • CD8 Positive T Cells: Interact with MHC I → T cytotoxic cells (kill infected or cancerous cells).
• Additionally, both types can differentiate into T regulatory cells, which help regulate immune responses and prevent autoimmunity.

T Cell Destinations

• After maturation, T cells move to secondary lymphoid organs south as:
  • Spleen: Forms periarteriolar lymphatic sheaths (white pulp).
  • Lymph Nodes: Localized in the deep part of the cortex.
• They can also be found in other areas: tonsils, mucosa-associated lymphoid tissue (MALT) in respiratory and urinary tracts.

Summary of the T Cell Development Process

1. Made in Red Bone Marrow.
2. Migrate to Thymus for Maturation:
   • Positive selection (recognize MHC).
   • Negative selection (avoid self-recognition).
3. Differentiate into Functional T Cell Types:
   • T helper, T cytotoxic, or T regulatory cells.
4. Travel to Secondary Lymphoid Organs to execute immune functions.