SUBJECT

T-Cell Ontogeny and the Cellular Immune Response

lecture

master

Faculty of Science

Biology MSc

2

Semesters 1-4

Autumn/Spring semester

1. General introduction. The position and function of various T-lymphocyte subpopulations, Tαβ, Tγδ and NKT cells in the immune system. Comparison of development, antigen-recognition and effector functions of T- and B-lymphocytes.

2. The structure and anatomy of the thymus. Significance of the thymic microenvironment in the T-cell development. The role of thymic and extrathymic MHC-pools in T-cell maturation (the MHC-restriction). The early pre-thymic phases of T-cell development and their transriptional regulation.

3. Structure of the genes encoding TcR chains, the origin of TCR diversity. Recombination of TcR genes: the basic mechanisms and their regulation. The Burnet clone-selection theory, the basic early models of thymocyte selection.

4. The positive and negative selection of immature T-cells: Principles, moleular bakcground and regulation. Qualitative and quantitative selection models: The modified “differential-avidity selection model”.

5. The positive selection: the self-peptide profile as a selection factor. Relationship between the selection and gene recombination processes. Significance of the pre-TCR signaling and TcR expression levels. Dual TcR-T-cells and their possible impact on the immune response.

6. Negative selection of DP thymocytes, the effector cell death meachanisms and their regulation. Significance of cytokine and Notch-signals in regulating the positive and negative selection processes.

7. The imperfect central tolerance: autoimmune T-cell subsets formed during the maturation. The role of avidity-based fine-tuning of maturating T-cells in formation of self-tolerance. The stochastic and instructive models of CD4+ vs. CD8+ T-cell differentiation. The new "signal-stregth and duration/kinetic“ model of SP T-cell formation. The extrathymic T-cell development.

8. Activation of peripheral T-lymphocytes. Antigen presenting cells, MHC molecules and the process of antigen presentation. The TCR–MHC connection, role of the coreceptors, the signal transduction cascade.

9. Adhesion, costimulator and cytokine molecules essential in activation and homeostasis of peripheral T-cells.

10. The T-cell ’homing’ processes and the controlling molecules.

11. Differentiation/polarization of TH effector cells and their special functional roles. The TH1 – TH2 balance and its role in the immune defense against pathogens or in pathological processes. Properties of inflammation-linked TH-17 és TH-25 cells.

12. The cytotoxic T-lymphocytes and their effector function. Comparison of CD4+ and CD8+ T-cell activation. Mechanisms operating in immunological synapses of cytotoxic effector T-cells with their target cells. The characteristic cytotoxic responses against various viral infections.

13. The T-cell memory. The naive, effector and memory T-cell populations: phenotypic and functional comparison.

14. Regulation of the immune response. The various regulatory and suppressor T-cell populations. Maturation of Treg cells in the thymus and their formation and function at the periphery. The role of Treg cells in maintaining peripheral tolerance.

• H. Spits: Development of αβ T cells in the human thymus. Nature Reviews Immunol., 2002. 2: 760-772

• L. Klein, B. Kyewski: Self-antigen presentation by thymic stromal cells: a subtle division of labor. Current Opinion in Immunology 2000. 12: 179-186.

• SM Anderton, DC Wraith: Selection and fine-tuning of the autoimmune repertoire., Nature Reviews Immunol. 2002. 2: 487-498.