Write short note on the following: a) Endogenous pathway of antigen presentation b) Positive T-cell Selection

Introduction

The immune system uses antigen presentation and T-cell selection processes to detect harmful invaders and develop immune memory. Two important concepts in immunology are the endogenous pathway of antigen presentation and positive T-cell selection. Let’s understand both of these in simple and clear terms.

a) Endogenous Pathway of Antigen Presentation

What is It?

The endogenous pathway is the process by which cells present internal (intracellular) antigens, such as viral or tumor proteins, to the immune system. This presentation is done using a molecule called MHC class I.

Steps of the Endogenous Pathway:

1. Protein Degradation: Proteins inside the cell (including viral proteins) are broken down into small fragments called peptides by a structure called the proteasome.
2. Peptide Transport: These peptides are transported into the endoplasmic reticulum (ER) by a transporter protein called TAP (Transporter associated with Antigen Processing).
3. MHC Class I Binding: Inside the ER, the peptides bind to MHC class I molecules.
4. Surface Expression: The peptide-MHC I complex is then transported to the cell surface.
5. Recognition: Cytotoxic T cells (CD8+ T-cells) recognize and bind to the peptide-MHC I complex and destroy the infected cell.

Why is It Important?

• It helps the immune system detect and destroy virus-infected or cancerous cells.
• It activates cytotoxic T-cells, which are crucial for cell-mediated immunity.

b) Positive T-cell Selection

What is It?

Positive selection is a key step in the development of T-cells (also called T lymphocytes) in the thymus. It ensures that only T-cells that can recognize self-MHC molecules survive.

Where It Happens:

In the cortex of the thymus, where immature T-cells (called thymocytes) interact with epithelial cells that display self-MHC molecules.

Steps of Positive Selection:

1. Thymocytes express both CD4 and CD8 co-receptors (double-positive).
2. They interact with epithelial cells in the thymus that present self-MHC molecules with self-peptides.
3. If a T-cell receptor (TCR) weakly binds to the self-MHC molecule, it receives a survival signal.
4. If the TCR fails to bind, the T-cell undergoes apoptosis (dies).
5. The surviving T-cells then become either CD4+ or CD8+ based on whether they interacted with MHC II or MHC I, respectively.

Why is It Important?

• Ensures that T-cells can recognize antigens presented by the body’s own MHC molecules.
• Prepares T-cells for future activation by antigen-presenting cells in the peripheral immune system.
• It’s a critical step in shaping a functional and self-tolerant T-cell population.

Conclusion

The endogenous pathway of antigen presentation allows the immune system to detect and eliminate infected or abnormal cells from within. Positive T-cell selection, on the other hand, is a developmental process that ensures T-cells can recognize the body’s own MHC molecules. Both processes are essential for building an effective and specific immune defense system.