slides on t-cells

1. Group 1
Members:
Muhammad Sajawal 08
Amna Hafeez 09
Asad Saeed 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)

6. T-CELL RECEPTOR
(TCR)

7. 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

8. 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

10. GENERATION OF TCR

11. 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.

12. Gene rearrangement

13. 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

15. T-cell maturation

16. 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

18. 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

20. 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.

22. T-cell Activation

23. • 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

26. T-cell differentiation