1. Dental Microbiology #211 IMMUNOLOGY 2006 Lecture 5 Cellular Immunity: The functions of T cells

2. Topics The Ag-specific T cell receptor
The T effector cells- what do they do and how
The immune responses in the oral cavity

3. Humoral and Cellular Immunity
The Antibodies and Complement constitute the Humoral arm of the immune response
The T cells and the Antigen-Presenting Cells constitute the Cellular arm of the immune response

4. Cell-mediated immunity is operated by T lymphocytes, and by Macrophages

5. The T lymphocyte
The T lymphocytes undergo maturation in the thymus from undifferentiated lymphoid progenitors that arrive from the bone marrow. T cells are characterized by the expression of antigen-specific T cell receptors (TCR).
T cells produce and express only the cell-bound molecules but not soluble forms of the TCR

6. Structure of the T cell Receptor Fig. 1
The TCR is composed of two polypeptide chains: the " (the L chain counterpart) and the $ (the H chain counterpart of Ig).
The extracellular portion of each chain has a variable (V) and constant (C) domain. Both chains have carbohydrate moieties (blue hexagons)
Each TCR molecule has only one binding site.

7. Two classes of T lymphocytes
Following a complex process of maturation in the thymus, T cells separate into two distinct populations:
They are called CD4+ and CD8+ T cells.
Mature T cells express either the CD4 or the CD8 molecule on their surface but not both, and perform distinct biologic functions.

8. CD4 and CD8 act as co-receptors Fig 2
The CD4 and CD8 molecules are called co-receptors because, when the T cell binds the Ag-MHC complex, they interact both with the TCR on the T cell surface and with the MHC on the APC

9. Effector T cells
The binding of Ag peptide-MHC complex present on an APC to the TCR starts a chain of intracellular signaling events that results in the activation, proliferation and conversion of a resting T cell into an effector T cell and a memory T cell
There are 3 types of effector T cells:
CD4+ T helper (Th)-1
CD4+ T helper (Th)-2
CD8+ Cytotoxic T lymphocytes (CTL)

10. The CD4 T helper cells help to organize the type and direction of the immune response through the production cytokines.
The CD8 CTL act by direct killing of the cells on the surface of which they encounter foreign Ag-MHC class-I
Th-1, Th-2 and CTL differ markedly in biologic function and in the type of cytokines they produce

11. Properties of Th-1 cells
CD4+ Th-1 cells produce the cytokines Interleukin-2 (IL-2), Interferon ( (IFN() and Tumor Necrosis Factor " and $ (TNF" and $)"at the site of infection. A typical effect of Th-1 cell activation is the defensive mechanism against infection with tubercle bacilli and other intracellular pathogens.
Th-1 cells are also involved in the reaction to foreign bodies called granulomas in which concentric layers of T cells, macrophages and fibroblasts surround and isolate the infected cells.

12. Effector function of T lymphocytes Fig. 3

13. Granuloma Fig 4
A core composed of infected macrophages and concentric layers of healthy macrophages, T cells and fibroblasts

14. Properties of Th-2 cells
CD4+Th-2 help B cells to produce antibodies,
Th2 cells produce the cytokines interleukin-4, 5, 6, 10 and 13. IL-4, 5 and 6 provide the Th-2 cells with the ability to help B cells to produce antibody.

15. T cell help for Ab formation by B cells Fig 5
B cells are also APC.
They pick up Ag via the BCR, internalize,
process and load the fragments onto MHC II.
Ag-MHC at the surface presents Ag to a Th cell
The Th2 cells secrete
IL4, IL5, IL6 etc which induces the B cell to produce Ab.

16. Effector function of T lymphocytes Fig. 6
Th2 cell interacts with Ag MHC-class-II on B cell surface and releases IL-4, IL-5, IL-6.
B cell divides then differentiates to become a plasma cell.
Plasma cell

17. Properties of CTL
CD8+CTL kill virus-infected cells, foreign tissue/organ grafts and also some tumor cells, by direct binding to the MHC class-I-Ag peptide complex expressed on the surface of the target cells.
The killing occurs through the focused release of toxic molecules called perforins and granzymes which penetrate into the target cell and destroy it.

18. Effector function of T lymphocytes Fig. 7

19. Cytotoxic Molecules of CD8+ T cells Fig 8
cytotoxic molecules are stored in intracellular granules. When a CD8+ T cell recognizes its target, the perforin molecules released from the granules polymerize on the surface of the target cell and form pores
Granzymes are released at the point of T cell-target cell contact and penetrate the target cell through the perforin-induced pores.

20. One CTL kills multiple targets Fig 9NT DT DT

21. Immune functions of different domains
The salivary domain provides the humoral components: the antibodies (IgA) and Complement
The gingival crevicular domain provides the inflammatory cells: PMN, macrophages, B and T lymphocytes, as well as most classes of antibodies

22. Immune activation Fig 10
Assume this is oral cavity and mandibular or parotidal lymph nodes.

23. Immune responses to pathogens
Dental carries: Streptococcus mutans : Mainly IgA antibodies in saliva.
Periodontal disease: CD4 effector T cells, macrophages and a few plasma cells can be detected even before the appearance of overt clinical signs.
Pulpal and Periapical lesions: mainly granuloma formation (CD4 T cells macrophages and fibroblasts). In severe cases there is bone destruction induced directly by the pathogen but also by the immune inflammatory process.

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