Ch. 10. T cell development Maturation - in thymus Activation Differentiation

1. Ch. 10. T cell development Maturation - in thymus Activation Differentiation Ch. 10

2. p. 245 Ch. 10

3. T cells migrate to thymus Positive selection of T cells that recognize self-MHC Negative selection of T cells that react too strongly with self-MHC (self-tolerance) Cell-surface protein expression changes Ch. 10

4. p. 247 Ch. 10

5. p. 248 Ch. 10

6. p. 249 Ch. 10

7. p. 250 Ch. 10

8. TH cell activation Central to CMI and humoral response (CMI=cell-mediated immunity) TCR-CD3 + Ag-MHC on target cell and many accessory molecules Resting T cell begins to go through cell cycle immediate genes- transcription factors intermediate genes- cytokines and receptors late genes- adhesion factors Ch. 10

9. p. 256 Ch. 10

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11. p. 257 Ch. 10

12. Naïve T cells: TCR-Ag-MHC is not enough Co-stimulatory signal: B7 on APC CD28 and CTLA-4 (on activated T cells) this can be circumvented in vitro Block B7 or CD28: clonal anergy Ch. 10

13. p. 259 Ch. 10

14. p. 260 Ch. 10

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19. p. 262 Ch. 10

20. p. 265 Ch. 10

21. p. 266 Ch. 10

22. Superantigens - bacterial, viral, endogenous Bind to TCR-MHC complex in nonspecific way, on the outside of the V-beta chain Certain V sequences are targets Ch. 10

23. p. 261 Ch. 10

24. Since any T cell with that V can be activated, reaction is polyclonal Cytokine overproduction Systemic toxicity Staphylococcus toxins- food poisoning, toxic shock syndrome Ch. 10

25. p. 261 Ch. 10

26. T cell differentiation CD4+ cells outnumber CD8+ cells 2:1 in the periphery More than 95% of peripheral T cells express the  receptor CD4+ cells recognize antigen complexed with MHC Class II antigen CD8+ cells recognize antigen complexed with MHC Class I antigen Ch. 10

27. Circulating “naïve” T cells circulate between blood and lymphoid tissues; circulation increases chance for antigen exposure Cells may circulate for many weeks or longer Ch. 10

28. What happens when a T cell is activated? Ag-MHC engaged with TCR-CD3 Co-stimulation with CD28-B7 interaction After 48 hours, cell begins to divide rapidly IL-2 gene transcription IL-2 receptor transcription IL-2 mRNA is stabilized By 4-5 days cells are ready to differentiate Effector cells Memory cells (more easily activated) Ch. 10

29. TH1 and TH2 subsets TH1- secretes IL-2, INF-, TNF- cell-mediated immunity TH2 –secretes IL-4, IL-5, IL-6, IL-10 B cell activation Memory T cells can persist for years Ch. 10

30. p. 263 Ch. 10

31. 1980s- a new population of T cells was discovered -TCR Rare in periphery Prominent in skin, gut and pulmonary epithelium Most of these cells express neither CD4 nor CD8 but one subset in intestinal epithelium of mice is CD8+ Ch. 10

32.  T cells, continued Cells seem to be tissue-fixed TCR diversity seems to be restricted; maybe they tend to respond to certain antigens How do they work? Many isolated reports; not too conclusive Respond to: bacterial antigens viruses heat shock proteins tumor cells Ch. 10

33. Summary T cells mature in the thymus. Self-reactive cells are eliminated through positive and negative selection. T cell activation requires the CD3-TCR complex as well as co-stimulatory signals. Most T cells express the  receptor. Ch. 10