50. Cytotoxic and helper T lymphocytes.

Overview of T Lymphocytes

• T lymphocytes are a type of white blood cell essential for the adaptive immune response.
• They do not attack pathogens directly. Instead, they act on other cells in the body, particularly those that present antigens.
• T cells only recognize antigens when these are displayed in combination with the body’s own MHC (Major Histocompatibility Complex) molecules.
• There are three main subtypes of T cells:
• Cytotoxic T cells (Tc): Also called T killer cells
• Helper T cells (Th): Guide and coordinate immune responses
• Regulatory T cells (Treg): Modulate and suppress the immune response (not covered in detail here)

Cytotoxic T Lymphocytes (T Killer Cells)

Main Function

• Cytotoxic T cells destroy cells that are infected by viruses.
• They do this by inducing the infected cells to self-destruct through a process called apoptosis.

Antigen Recognition

• Tc cells recognize antigens only when they are presented on MHC class I molecules.
• MHC class I molecules are found on the surface of all nucleated cells, making all such cells potential targets for virus infection.

Key Surface Marker

• Tc cells express a protein called CD8, which helps them interact specifically with MHC class I molecules.
• CD8 serves both as a co-receptor and a marker to identify cytotoxic T cells.

Antigen Processing for Tc Cells

• The antigens presented on MHC class I molecules come from proteins that are made inside the cell, such as viral proteins during infection.
• These proteins are broken down by a cellular machine called the proteasome into short peptides (8–10 amino acids).
• These peptides are transported into the endoplasmic reticulum (ER) by a protein called TAP.
• Inside the ER, MHC class I molecules bind these peptides and carry them to the cell surface to be displayed.

Mechanisms of Killing

• Tc cells kill infected cells using two main pathways:

1. 1. Fas-FasL pathway:

• Tc cells express a protein called FasL.
• FasL binds to its receptor Fas on the target cell, triggering a cascade of signals that activates enzymes called caspases which lead to apoptosis.

1. 2. Perforin-Granzymes pathway:

• Tc cells release perforins, which create pores in the target cell’s membrane.
• Through these pores, granzymes enter the cell and activate the internal machinery that causes apoptosis.
• If apoptosis is blocked by a virus, extensive membrane damage from perforins can lead to necrosis, a more chaotic form of cell death.

Specificity and Selectivity

• All nucleated cells present many peptide-MHC class I complexes.
• Tc cells ignore complexes made of normal self-proteins.