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Development of Thymus

Development of Thymus. Bone marrow cells colonize thymic anlage in fetus. Fully Developed Thymus. Waves then Steady state. Involutes after puberty. Precursor chooses. preTCR. CD3. Specific Distribution of Cells. Maturation of T cells. Critical function of the thymus

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Development of Thymus

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  1. Development of Thymus Bone marrow cells colonize thymic anlage in fetus

  2. Fully Developed Thymus

  3. Waves then Steady state Involutes after puberty

  4. Precursor chooses

  5. preTCR

  6. CD3

  7. Specific Distribution of Cells

  8. Maturation of T cells • Critical function of the thymus • Occurs in several steps • T cells must acquire a functional TCR • TCR genes must productively rearrange • MatureT cells must express one co-receptor • T cells must acquire other molecules necessary for their function • Interaction with stromal cells is crucial

  9. Dead cells Apoptosis

  10. Medulla Second function of thymus is Selection Occurs in 2 stages

  11. Positive Selection

  12. Positive selection mediated by cortical epithelial cells

  13. Negative selection mainly mediated by dendritic cells and macrophages

  14. Negative Selection

  15. * Aire induced by LT Express self proteins made outside thymus Role of Medullary Epithelial Cells in Negative Selection

  16. Negative selection occurs before single positive stage

  17. surviving cells

  18. Choice of Co-receptor p56 lck Notch-1

  19. Notch-1 belongs to gene family important for embryonic development of tissues Ligand Delta-like-1 expressed by stromal cells Notch-1 signaling may be important at critical transitions Mutated Notch-1 -> major decrease in DN cells

  20. Class I Stromal DN T Cell TCR Cell Class II CD3 IL-7 & SCF Requirements for T Cell Development RAG-1 & 2, p56 lck, Transcription factors, Notch-1

  21. Requirements for T Cell Development p56 lck & ZAP-70, Th-POK AIRE & LT

  22. starts

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