Understanding T-Cell Development Process

Sep 25, 2024

T-Cell Development Lecture Notes

Overview

  • This lecture covers the process of T-cell development.
  • Key locations involved: Red bone marrow and Thymus gland.

T-Cell Production

  • Red Bone Marrow:
    • T-cells are produced here from lymphoid stem cells.
    • Precursor T-cells (immature) are formed.

Thymus Gland

  • Location:
    • Overlies the heart, located in the mediastinum (thoracic cavity).
  • Function:
    • Primary lymphoid organ for T-cell maturation.
    • Active during infancy, childhood, and early adolescence; atrophies after adolescence.

Migration to Thymus

  • Precursor T-cells enter the bloodstream.
  • Directed to the thymus by chemokines such as:
    • Thymocin
    • Thymotaxin
    • Thymopoietin
    • Generalized Thymic Factors

Maturation Process

Activation of T-Cell Genes

  • Thymic cells secrete chemicals that activate T-cell genes, producing:
    • RAG1 and RAG2: Recombination activating genes that shuffle DNA and produce T-cell receptors (TCR).
  • TCRs are necessary for recognizing foreign antigens.

Cluster Differentiation Proteins

  • Activation also leads to the production of CD proteins:
    • CD4 (T-helper cells)
    • CD8 (T-cytotoxic cells)

Selection Process

Positive Selection

  • TCRs recognize MHC (Major Histocompatibility Complex) molecules on thymic cells:
    • MHC Class I interacts with CD8
    • MHC Class II interacts with CD4
  • If T-cells bind correctly, they survive (positive selection).
  • If they fail to bind, they undergo apoptosis.

Negative Selection

  • TCRs must not recognize self-antigens.
  • If they do, they undergo apoptosis to prevent autoimmune responses.

Final Differentiation

  • Based on random interactions, T-cells differentiate into:
    • T Helper Cells: CD4+ (interact with MHC II)
    • T Cytotoxic Cells: CD8+ (interact with MHC I)
    • T Regulatory Cells: Can arise from both T Helper and T Cytotoxic cells.

Destinations of Mature T-Cells

  • Can migrate to secondary lymphoid organs:
    • Lymph Nodes: Park in the deep cortex.
    • Spleen: Form white pulp around sinusoidal capillaries.
    • Thymus: T regulatory cells concentrated in Hassall's corpuscles.
    • Other areas: Tonsils, mucosa-associated lymphatic tissue.

Summary

  • T-cells originate in the red bone marrow, mature in the thymus, and migrate to various secondary lymphoid organs to perform their functions.