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Chapter 14- Cell-mediated responses

Chapter 14- Cell-mediated responses. Where we’re going with this chapter: Understanding “effector” cells- and how they are different from naïve cells. The CTL killing process- apoptosis. NK cells ADCC How we test these things. Die, you horrible traitor!. AAAAGH!.

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Chapter 14- Cell-mediated responses

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  1. Chapter 14- Cell-mediated responses • Where we’re going with this chapter: • Understanding “effector” cells- and how they are different from naïve cells. • The CTL killing process- apoptosis. • NK cells • ADCC • How we test these things

  2. Die, you horrible traitor! AAAAGH!

  3. Think of “effector” cells as the ones doing the job- the “non-activated” effector cells would be memory cells, waiting to be activated; or a cell that has stopped responding, but has been restimulated. This form activates lyk and fyn better!

  4. Macrophage and inflammation activators!

  5. The CTL response- an older version, but useful Note that it’s not necessarily the same Ag stimulating the Th1 as stimulating the Tc cell- the Tc cell just needs the IL2- but see next slide! The activation step makes it responsive to IL2

  6. “Licensing” of an APC • Dendritic cells appear to serve as “gatekeepers”- making sure that we’re not activating CTL’s improperly- perhaps against self-ag’s. The APC is “licensed” to present to a CTL-P, after being bound and stimulated by a Th1 cell.

  7. This might be a virally-infected dendritic cell that’s also engulfed the same virus- so it’s doing both class I and class II ag presentation. Or, it get’s licensed by having its TLR’s activated.

  8. Cool ways of tracking CTLs

  9. The peptides is the same on all MHC I’s isolated

  10. Key point- they’re NOT in the lymph nodes- out finding/killing infected cells!

  11. The gory details on killing (if it makes you feel better, killer T cells don’t actually kill cells; they persuade them to commit suicide)

  12. What do these look like??

  13. Perforin holes!

  14. Two pathways- granzymes and FAS Granzymes and FAS both work- alternate routes to the same effect

  15. Once we generate the CTL’s we then use them in a killing assay

  16. Natural Killer cells

  17. NK’s are an early, innate response!

  18. Cute, but sad, mice w/o an adaptive immune system, surviving on their NK’s!

  19. How we think NK’s kill First, they kill like CTL’s kill- granzymes, Fas ligand, etc. The Q is – how do they pick their victims (er, targets)?

  20. ADCC • Antibody-dependent cell-mediated cytotoxicity • Lots of different cells can do it- • A non-specific cell kills specifically due since the ab is specific. • Hydrolytic and granzymes released- probably locally.

  21. Killing/activation assays We’ve actually done these before, but that’s OK! If Kuby does it twice, WE can do it twice!

  22. This would be an MHC difference response, vs. one to a specific antigen that was used to show MHC restriction.

  23. Specific, MHC restricted response Allogeneic response

  24. Things to know from Ch 14 • What’s an effector cell? • Activation/proliferation of Tc cells, differentiation into CTLs. • Killing- FAS, FAS ligand, perforins, granzymes, caspases, mitochondria • NK’s- when do they respond, how do they kill • ADCC- cells involved, Fc receptor • Assays for proliferation and killing.

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