A kidney-transplant patient experienced a cytotoxic rejection of the new kidney. Place the following in order for that rejection: (1) apoptosis occurs; (2) CD8⁺ T cell becomes CTL; (3) granzymes released; (4) MHC class I activates CD8⁺ T cell; (5) perforin released.
a. 1, 2, 3, 4, 5
b. 5, 4, 3, 2, 1
c. 4, 2, 5, 3, 1
d. 3, 4, 5, 1, 2
e. 2, 3, 4, 1, 5

Verified step by step guidance

1. Identify the role of CD8⁺ T cells in cytotoxic rejection, which involves recognizing and destroying infected or foreign cells.
2. Understand that MHC class I molecules present antigens to CD8⁺ T cells, activating them.
3. Recognize that once activated, CD8⁺ T cells differentiate into cytotoxic T lymphocytes (CTLs).
4. Know that CTLs release perforin, which forms pores in the target cell membrane.
5. Realize that granzymes enter through these pores, leading to apoptosis of the target cell.

Key Concepts

CD8⁺ T Cells and Cytotoxicity

CD8⁺ T cells, also known as cytotoxic T lymphocytes (CTLs), play a crucial role in the immune response by recognizing and killing infected or cancerous cells. Upon activation, they differentiate into CTLs capable of inducing apoptosis in target cells. This process is essential in transplant rejection, where the immune system identifies the transplanted organ as foreign.

MHC Class I Molecules

Major Histocompatibility Complex (MHC) class I molecules are proteins found on the surface of all nucleated cells that present endogenous antigens to CD8⁺ T cells. The interaction between MHC class I and the T cell receptor (TCR) is critical for the activation of CD8⁺ T cells, leading to their proliferation and differentiation into CTLs, which are necessary for targeting and destroying foreign cells.

Mechanism of CTL-Induced Apoptosis

The mechanism by which CTLs induce apoptosis in target cells involves the release of cytotoxic granules containing perforin and granzymes. Perforin forms pores in the target cell membrane, allowing granzymes to enter and trigger apoptotic pathways. This sequence of events is vital in the context of transplant rejection, as it leads to the destruction of the transplanted tissue.