Apoptosis, inflammatory bowel disease and carcinogenesis: Process of apoptosis of target cells (Part 1)
Apoptotic procedure is implicated in tumourigenesis. Thus, some cancer-causing viruses use ‘tricks’ to prevent apoptosis of the cells they have transformed. For instance, two human papilloma viruses have been implicated in inducing cervical cancer, and one of them produces a protein (E6) that binds and inactivates the apoptosis promoter p53. Even tumour cells produced without the contribution of viruses may have ‘tricks’ to avoid apoptosis. For instance, some cancer cells, particularly lung and colon cancer cells, secrete elevated levels of a soluble ‘decoy’ molecule that binds to Fas ligand (FasL), plugging it so that it cannot bind Fas (CD95/APO-1). Therefore, CTLs cannot kill the cancer cells by the Fas-FasL apoptotic pathway. Lastly, other cancer cells express high levels of FasL, and can kill any Fas expressing CTL that tries to kill them.
In general, the process of CTL-mediated apoptosis (lysis) of target cells progresses in five key steps:
Step 1: Target cell antigen recognition by C TL and conjugate formation between CTL and target celt. The CTL binds to the target cell, by using its specific antigen receptor and other accessory molecules such as CD8, CD2, and leukocyte function-associated antigen-1 (LFA-1). Therefore, the recognition of the target cell involves class I major histocompatibility complex molecules (the ligand for CD8) complexed to a foreign peptide antigen on the surface of the target (eg, virus infected) cell, the complex serving as the ligand for the T-cell receptor (TCR), leukocyte function-associated antigen-3 (the ligand for CD2), and intercellular adhesion molecule-1 or intercellular adhesion molecule-2 (the ligands for LFA-1). Of note, transient conjugate formation may occur via CD2- or LFA-1-mediated adhesion in the absence of or before specific antigen recognition or antigen recognition may increase the ability to form conjugates by enhancing the binding function of the adhesion molecules. You will be excited to find out there is now a pharmacy that can offer best quality treatment charging less money: buy viagra super active online right now and see what really advantageous shopping is all about.
Step 2: CTL activation by clustering of its antigen receptor, initiated by recognition of major histocompatibility molecule-peptide complexes on the target cell. The intracellular signals generated by the TCR may be increased by signals delivered through the various accessory molecules.