1. Kindt • Goldsby • Osborne
Kuby IMMUNOLOGY
Sixth Edition
Chapter 14
Cell-Mediated Cytotoxic Responses
宜蘭大學 動物科技系 免疫學
王愈善
Copyright © 2007 by W. H. Freeman and Company

2. Outline Effector Responses General Properties of Effector T Cells
Cytotoxic T Cells
Natural Killer Cells
NKT cells
Antibody-Dependent Cell-Mediated Cytotoxicity
Experimental Assessment of Cell-Mediated Cytotoxicity

3. Outline Effector Responses General Properties of Effector T Cells
Cytotoxic T Cells
Natural Killer Cells
NKT cells
Antibody-Dependent Cell-Mediated Cytotoxicity
Experimental Assessment of Cell-Mediated Cytotoxicity

4. Effector Responses
The principal role of cell-mediated immunity is to detect and eliminate cells that harbor intra-cellular pathogens.
Cell-mediated immune responses can be divided into two major categories A. direct cytotoxic activity B. effector CD4+ T cells that mediates delayedtype hypersensitivity reactions
p.352, left column

5. Outline Effector Responses General Properties of Effector T Cells
Cytotoxic T Cells
Natural Killer Cells
NKT cells
Antibody-Dependent Cell-Mediated Cytotoxicity
Experimental Assessment of Cell-Mediated Cytotoxicity

8. Outline Effector Responses General Properties of Effector T Cells
Cytotoxic T Cells
Natural Killer Cells
NKT cells
Antibody-Dependent Cell-Mediated Cytotoxicity
Experimental Assessment of Cell-Mediated Cytotoxicity

9. Generation of effector CTLs1 2 3

10. Proliferation of memory CTL-Ps may not require help from TH cells.

11. MHC tetramers p.355, left column
A given MHC-tetramer–peptide complex binds only CD8+ T cells that have TCRs specific for the particular peptide-MHC complex.
p.355, left column

12. Localizing antigen specific CD8+ T-cell populations in vivo

13. Scanning electron micrograph of tumor-cell attack by a CTL

14. Stages in CTL-mediated killing of target cells
TCR-CD3/MHC I
LFA-1/ICAMs

15. Antigen-mediated CTL activation converts LFA-1 from a low-avidity state to a high-avidity state

16. Formation of a conjugate between a CTL and target
2 min
10 min
Formation of a conjugate between a CTL and target
cell and reorientation of CTL cytoplasmic granules

17. CTL-mediated pore formation in target-cell membrane

19. Experimental demonstration that CTLs use Fas and perforin pathways

20. All of the CTL-mediated killing they observed could be traced to the action of perforin-dependent killing, Fas-mediated killing, or a combination of the two. No other mechanism was detected.
p.358, right column

21. Two pathways of target-cell apoptosis stimulated by CTLs
mannose 6-phosphate
receptors

22. Outline Effector Responses General Properties of Effector T Cells
Cytotoxic T Cells
Natural Killer Cells
NKT cells
Antibody-Dependent Cell-Mediated Cytotoxicity
Experimental Assessment of Cell-Mediated Cytotoxicity

24. Family of RAG-1 KO mice
These mice have no adaptive immunity because they lack T and B cells.

25. NK cells differ from CTLs in several significant ways
NK cells do not express antigen specific T-cell receptors or CD3.
Recognition of target cells by NK cells is not MHC restricted.
NK-cell activity does not increase after a second injection with the same tumor cells. In other words, the NK-cell response generates no immunologic memory.
p.362, left column

26. Opposing-signals model of how cytotoxic activity of NK cells is restricted to altered self-cells.

27. MHC-KIR gene combinations influence health
Human KIR A haplotype

29. Outline Effector Responses General Properties of Effector T Cells
Cytotoxic T Cells
Natural Killer Cells
NKT cells
Antibody-Dependent Cell-Mediated Cytotoxicity
Experimental Assessment of Cell-Mediated Cytotoxicity

30. NKT cells NKT cells is considered part of the innate immune system.
The T-cell receptor on the human NKT cell is invariant.
The TCR on NKT cells does not recognize MHC-bound peptides
NKT cells do not form memory cells
NKT cells do not express T-cell markers but do express NK-cell markers p

31. Outline Effector Responses General Properties of Effector T Cells
Cytotoxic T Cells
Natural Killer Cells
NKT cells
Antibody-Dependent Cell-Mediated Cytotoxicity
Experimental Assessment of Cell-Mediated Cytotoxicity

33. Outline Effector Responses General Properties of Effector T Cells
Cytotoxic T Cells
Natural Killer Cells
NKT cells
Antibody-Dependent Cell-Mediated Cytotoxicity
Experimental Assessment of Cell-Mediated Cytotoxicity

34. Experimental Assessment of Cell- Mediated Cytotoxicity
The mixed-lymphocyte reaction (MLR) is an in vitro system for assaying TH-cell proliferation in a cell mediated response
Cell-mediated lympholysis (CML) is an in vitro assay of effector cytotoxic function
The graft-versus host reaction (GVH) in experimental animals provides an in vivo system for studying cell-mediated cytotoxicity.

36. Curve 0 = no class II MHC differences
Curve 1 = one class II MHC difference
Curve 2 = two class II MHC differences

38. CTL or NK cells activity assay
1.Cr-51 release assay
(sample cpm ─ spontaneous cpm)
 100%
(maximal cpm ─ spontaneous cpm)

39. The GVH Reaction Is an Indication of Cell-Mediated Cytotoxicity
The recipients, especially neonatal ones, often exhibit weight loss.
The intensity of a GVH reaction can be assessed by calculating the spleen index as follows:
p.368, left column

40. Outline Effector Responses General Properties of Effector T Cells
Cytotoxic T Cells
Natural Killer Cells
NKT cells
Antibody-Dependent Cell-Mediated Cytotoxicity
Experimental Assessment of Cell-Mediated Cytotoxicity

41. Study question
You have a monoclonal antibody specific for LFA-1.You perform CML assays of a CTL clone, using target cells for which the clone is specific, in the presence and absence of this antibody. Predict the relative amounts of 51Cr released in the two assays. Explain your answer.

42. Study question
A mouse is infected with influenza virus. How could you assess whether the mouse has TH and TC cells specific for influenza?
Explain why NK cells from a given host will kill many types of virus-infected cells but do not kill normal cells from that host.