T-lymphocytes and generation

slides on t-cells

1. Group 1 Members: Muhammad Sajawal 08 Amna Hafeez 09 Asad S aeed 13 Muqadas shehzad 17 Hadia Azhar 29 Muhammad Shaffique 33 Farwa Dogar 34 Firdous Dilshad 39

2. T-Lymphocytes Topic: Generation Maturation Activation Differentiation

3. T-lymphocytes type of lymphocyte (a subtype of white blood cell) that plays a central role in cell-mediated immunity . t-cells can be distinguished from other lymphocytes by the presence of a T-cell receptor on the cell surface . They are called T cells because they mature in the thymus gland.

4. Types of T-cells 1. T-helper cells ( Th cells) 2. Cytotoxic T-cells ( Tc cells) 3. Memory T-cells 4. Regulatory T-cells ( treg )

5. T-CELL RECEPTOR (TCR)

6. T-cell receptor found on the surface of T cells, or T lymphocytes responsible for recognizing fragments of antigen as peptides bound to major histocompatibility complex (MHC) molecules. 95 % of T cells the TCR consists of an alpha (α) chain and a beta (β) chain 5% of T cells the TCR consists of gamma and delta (γ/δ) chains

7. Structure of TCR variable alpha (α) and beta (β) chains Each chain is composed of two extracellular domains: Variable (V) region and a Constant (C) region The Constant region is proximal to the cell membrane, followed by a transmembrane region and a short cytoplasmic tail, while the Variable region binds to the peptide/MHC complex . Similar to Fab region of antibody structure

8. GENERATION OF TCR

9. Gene rearrangement TCR gene segments resembles that at the immunoglobulin loci, with separate variable (V), diversity (D), joining (J) gene segments, and constant (C) genes. TCRα- and β-chain genes are composed of discrete segments that are joined by somatic recombination during development of the T cell The α and β chains pair after their biosynthesis to yield the α:β T-cell receptor heterodimer .

10. Gene rearrangement

11. CD4 and CD8 Co-receptors glycoproteins found on the surface of T cells Both have abilities to recognize peptide-MHC complex and signal transduction CD4 : CD4 T-cells recognize antigen combined with MHC class II , function largely as helper cells Four domains (D1-D2) and a cytoplasmic chain CD8 : CD8 T-cells recognize antigen combined with MHC class I , function as cytotoxic cells Contain α and β chains, disulfide linked

12. T-cell maturation

13. T-cell maturation All T cells originate from hematopoietic stem cells in the bone marrow . The earliest thymocytes express neither CD4 nor CD8, and are therefore classed as double-negative (CD4−CD8−) cells. As they progress through their development, they become double-positive thymocytes (CD4+CD8+), and finally mature to single-positive (CD4+CD8− or CD4−CD8+) thymocytes that are then released from the thymus to peripheral tissues . About 98% of thymocytes die during the development processes in the thymus

14. Positive selection: Takes place in cortical region of thymus Positive selection "selects for" T cells capable of interacting with MHC. Double-positive thymocytes (CD4+/CD8+) move deep into the thymic cortex, where they are presented with self-antigens . only those thymocytes that interact with MHC-I or MHC-II appropriately, will receive a vital "survival signal". All that cannot , will die by "death by neglect" (no survival signal). A thymocyte's fate is determined during positive selection. T-cell maturation

15. T-cell maturation Negative selection: Negative selection removes thymocytes that are capable of strongly binding with "self" MHC peptides . Thymocytes that interact too strongly with the self-antigen receive an apoptotic signal that leads to cell death. The remaining cells exit the thymus as immature naïve T cells This process is an important component of central tolerance and serves to prevent the formation of self-reactive T cells that are capable of inducing autoimmune diseases in the host.

16. T-cell Activation

17. Activation of Th cell is initiated by interaction of TCR with a processed antigenic peptide bound to MHC II on APC Initiates a cascade of biochemical events engagement of co-stimulatory molecules. Th -cell Activation

18. T-cell differentiation