1. Part IV
The adaptive
immune response
Chapter 9
T Cell-Mediated Immunity

2. APC 2

3. Periphery Naïve Effector Activated Ag-specific T cell response
Each with different Ag specificity
Naïve
Low frequency
Periphery
Ag-specific T cell response
Effector
Clonal expansion Ag
Activated
Ag-specific T

4. Effector T cells in CMI and humoral immunity
Effector T subsets

5. CD4 T cell differentiation Treg
Th17
Treg
Promote
local
inflammation
CMI: CD8 T
Humoral response

6. From inflammatory site
Entry of APC and naïve T cells into
peripheral lymphoid organs
Priming of naïve T cells by DC
Effector T cell response

7. Professional APC 7

8. DC subsets
cDC (CD11chi)
pDC
Viral infection

9. Entry of DC

10. DC maturation / differentiation / migration
Licensing
DC maturation / differentiation / migration

11. Lymphocyte entry into LN from blood
HEV
Adhesion molecules
Adhesion molecules

12. Lymphocyte entry into LN from blood
CCR7
CCL21
T zone: CCL21, CCL19
SLC: Secondary lymphoid tissue chemokine

13. Entry of APC (DC) and naïve T cells into peripheral lymphoid organs
Priming of naïve T cells by DC
Priming
The activation
and differentiation
of naïve T cells
Signal 1, 2, 3
Clonal expansion
& differentiation

14. Naïve T cell activation in peripheral lymphoid organs Naïve Activated
Ag specificity
Naïve T cell
activation
in peripheral
lymphoid
organs
Naïve
Activated
Effector

15. Periphery Naïve Effector Activated Ag-specific T cell response
Each with different Ag specificity
Naïve
Low frequency
Circulation
Periphery
Ag-specific T cell response
Effector
Clonal expansion Ag
Activated
Lymph nodes
Ag-specific T

16. Activation of LFA1
Signal 1 16

17. Three signals
in naïve T cell
activation
Signal 2: proliferation

18. Amount of Ag expression
T cell activation
Amount of Ag expression
T-APC
Avidity
Supramolecular activation compolex (SMAC) 18

19. Signal 1+2
CD28-dependent clonal expansion of CD4 T cells
IL2
CD25

20. Signal 1+2
IL2 autocrine
for CD4 T
clonal
expansion

21. Naïve T cell activation in peripheral lymphoid organs Naïve
Ag specificity
Naïve T cell
activation
in peripheral
lymphoid
organs
Naïve

22. Activation of LFA1
Signal 1 22

23. Regulation of
signal 2

24. Signal 1 alone
in LN?
Clonal deletion
Clonal anergy
Self tolerance

25. Type of
Ag-specific
effector

26. Signal 3: differentiation
Transcription factor
Adaptive Treg

27. CD4 T-dependent CD8 T cell activation
IL2
DC (APC) activation
CD40L-CD40
CD8 T
Colgate Immunology (and Virology) Blog

28. Ag

29. Ag capture and preservation by subcapsular sinus macrophage
CXCR5
Low phagocytosis
CXCL13
CCL21
Ag –nonspecific
B cells

30. Ag-specific stimulation
B-T cell
interaction
CCR7
induction
B cell as APC

31. CD4 T activation
Within LN
Egress

32. Egress
S1P R
Plasma:
Sphingosine 1-phosphate
(S1P) 32

33. Sphingosine-1-phosphate (S1P)
The AOCS Lipid Library
An important cellular
metabolite in animal cells
A ceramide-derived phospholipid

34. Blood mononuclear cells, Neutrophils, Erythrocytes.
S1P producer:
Blood mononuclear cells,
Neutrophils,
Erythrocytes.
Efficiently phosphorylate exogenously added sphingosine and discharge S1P into the medium, which suggests a general contribution of hematopoietic cells in maintaining plasma S1P levels.
It is relatively insoluble in aqueous solution.
Most of the plasma S1P is bound to carriers such as albumin.

35. Entry of APC (DC) and naïve T cells into peripheral lymphoid organs
Priming of naïve T cells by DC
Signal 1, 2, 3
Clonal expansion
& differentiation
Egress

36. Homing
Migration of
effector T cells to
inflammatory site

37. Entry of APC and naïve T cells into peripheral lymphoid organs
Priming of naïve T cells by DC
Effector T cell response
Homing
CD8 T cytotoxic response
CD4 T effector & Macrophage activation

38. Homing Addressin Guiding lymphocytes to tissues
Ig domain
Vascular addressin (VA) 38

39. Ag-specific recognition of CD8 T cells

40. Requirement of signal 2
for effector function?
No signal 2
is required

41. Microtubule-organizing center
Cytotoxic mechanisms of CD8 T cells
Microtubule-organizing center
Cytotoxic granules

42. Membrane effector molecule
CTL

43. Effector
molecules
Membrane molecules
Soluble mediators

44. APC
Professional APC

45. Macrophage activation & CD4 T activation

46. Macrophages
activation by Th1

47. Reciprocal
activation

48. Th1 effectors
tissue

49. Effector T cells
recruitment 49

50. Lymphocyte activation Apoptosis of effectors
Signal 1-3
Lymphocyte activation
Innate
immunity
Effector
response
Apoptosis of effectors