1. Cell-Mediated Immunity CMI
Specialized lymphocytes, mostly T cells, respond to intracellular Ags
After differentiating in the thymus, T cells migrate to lymphoid tissue
T cells differentiate into effector T cells when stimulated by an Ag
Some effector T cells become memory cells

2. T Cells Helper T Cells (CD4, TH) Cytotoxic T Cells (CD8, TC)
TH1 Activate cells related to cell-mediated immunity
TH2 Activate B cells to produce eosinophils, IgM, and IgE
Cytotoxic T Cells (CD8, TC)
Destroy target cells with perforin

3. T Cells Delayed Hypersensitivity T Cells (TD) (CD4)
Associated with allergic reaction, transplant rejection, and tuberculin skin test
Suppressor T cells (TS) (CD8)
Turn off immune response when Ag no longer present

4. Structure of T Cell Receptor
CHO
Variable region “V”
Constant region “C”
Hinge “H”
Alpha chain
Beta
chain
Disulfide bridge
Transmembrane region
Cytoplasmic tail +

5. Structure of T Cell Receptor (TCR)
Two polypeptide chains, α and β, of roughly equal length
Both chains consist of a variable (V) and a constant (C) region
α chain V region has a joining (J) segment
β chain V region has both a J and diversity (D) segment

6. Structure of T Cell Receptor (continued)
Hypervariable regions in V contribute to diversity of TCR
TCR recognizes portions of MHC molecule and peptide bound in the groove

7. What Does the T Cell Receptor (TCR) Recognize?
Only fragments of proteins (peptides) associated with MHC molecules on surface of cells
Helper T cells (TH) recognize peptide associated with MHC class II molecules
Cytotoxic T cells (Tc) recognize peptide associated with MHC class I molecules

8. Interactions of TH Cell and APC
T helper
lymphocyte
TCR
LFA-2
LFA-1
CD28
TNF-alpha
IL-1
IL-6
IL-12
IL-15
TNF-beta
IFN-gamma
GM-CSF
IL-4
CD4
peptide
Antigen-
presenting
cell
LFA-3
ICAM-1
Class II
MHC
B7-1/B7-2
(CD80/CD86

9. Interactions of Tc Cell and Target Cell
T cytotoxic
lymphocyte
LFA-1
TCR
LFA-2
CD8
peptide
Target
cell
ICAM-1
Class I
MHC
LFA-3

10. T-independent Antigens
B cell
Figure 17.17

11. T-Dependent Antigens
Figure 17.16

12. T-dependent and independent antigens

13. Self MHC Restriction
T cells recognize foreign antigen associated with self MHC
No value for individual to have T cells that recognize foreign antigen associated with foreign MHC
Self MHC restriction occurs in thymus

14. Process of Self MHC Restriction in Thymus
T cells with TCR recognizing self MHC molecules are retained – “positive selection”
Retained T cells with TCR recognizing self peptide associated with self MHC are eliminated – “negative selection”
Self MHC-restricted T cells are released

18. Dendritic cells present antigens
Figure 17.12

22. Helper T Cells
Figure 17.13

23. Cell-mediated Cytotoxicity
Figure 17.14

24. Nonspecific Cells
Activated macrophages: Macrophages stimulated by ingesting Ag or by cytokines
Natural killer cells: Lymphocytes that destroy virus-infected cells, tumor
Figure 17.15

25. Self MHC Restriction in the Thymus
4 -
8 low
4 low
8 low
Sub-capsular region
Productive TCR
rearrangement
Non-productive TCR
rearrangement
APOPTOSIS
TCR
Not recognise self MHC
Recognise self MHC
macrophage
TCR
TCR recognises self antigens
Cortex
TCR does not recognise self antigens
Negative selection
Cortico-medullary region
TCR
TCR
vessel
Medulla

26. Self MHC Restriction in the Thymus4- 8-
4+/- 8+
4+ 8+
TCR low
Express
MHC I
MHC II
No MHC
engagement
apoptosis
TCR high 4+

27. Self MHC Restriction in the Thymus
No interaction
with self antigen
Interaction with MHC I
and self antigen. Interaction with dendritic cells, macrophages and medullary epithelium
Interaction with MHC II 8+
TCR high 4+
TCR induced apoptosis
Mature T cell pool

28. Self MHC Restriction in the Thymus

29. T-Cell clonal selection Animation

30. Superantigens Proteins produced by pathogens
Not processed by antigen presenting cells
Intact protein binds to variable region of β chain on TCR of T cells and to MHC class II on antigen presenting cells (APC)
Large numbers of activated T cells release cytokines having pathological effects

31. Conventional Antigen Superantigen αC βC βV αV α2 β2 β1 α1 MHC Class II
CHO βV αV α2 β2 β1 α1
MHC Class II
T cell receptor
Antigen
Super
antigen
T lymphocyte
Antigen presenting cell