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Reminders

Reminders. Case Studies: Due Wed., March 19 Exam 3- Wed., March 26 Chapters 3, 5, & 6. T cell Development. Chapter 5. Progenitor T Lymphocytes travel from the BM to the thymus for T cell development. Thymus Structure. Apoptotic cells in red. Macrophages in blue.

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Reminders

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  1. Reminders • Case Studies: • Due Wed., March 19 • Exam 3- Wed., March 26 • Chapters 3, 5, & 6.

  2. T cell Development Chapter 5

  3. Progenitor T Lymphocytes travel from the BM to the thymus for T cell development.

  4. Thymus Structure

  5. Apoptotic cells in red. • Macrophages in blue. ~ 98% of developing thymocytes undergo apoptosis.

  6. * Strategies to follow the stages of T cell development: • Status of the TCR genes. • Expression of enzymes: • RAG1 / RAG2 • Surface markers: • TCR: a & b chains • CD3 complex • CD4 or CD8 • CD25: IL2R a chain • CD44: Cell Adhesion

  7. Stage 1 of Development- Making the TCR Immature double negative thymocytes develop into double positive thymocytes expressing a TCR-

  8. Pre-TCR TCR + selection - selection Immature DN thymocytes develop into DP thymocytes expressing a TCR-

  9. DN1 DN2 DN3 “Double negative” CD3- 4- 8- 1st rearrangement Kit+ DN4 1 week CD3+ T cell Progenitor enters outer cortex- does not express markers Pre-TCR CD4+8+ “Double Positive” 2nd rearrangement

  10. DN3 DN3

  11. 80% T cells have productive b-chain rearrangement. If both rearrangement are unproductive on the 1st chromosome, the 2nd chromosome can rearrange.

  12. The a chain may undergo several rearrangement on each chromosome. Expression of the new alpha chain does not immediately block the other chromosome recombination.

  13. Stage 2 of Development: Selection of the T cell Repertoire. 1-2 % of T cells will carry a productive TCR that will survive + & - selection.

  14. Positive Selection: • Must select for those TCR that are able to interact with self MHC. • Negative Selection: • Eliminate: • T cells that recognize self antigen too strongly. • T cells that bind too strongly to self MHC

  15. Experimental Evidence for Positive selection:

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