China
Africa
Explore chapters and articles related to this topic
Introduction to basic immunology and vaccine design
Published in Amine Kamen, Laura Cervera, Bioprocessing of Viral Vaccines, 2023
Alaka Mullick, Shantoshini Dash
The other important type of T-cells are the cytotoxic T-cells. This type of T-cell attacks abnormal cells, such as those infected by a virus. Intracellular proteolytic fragments of a pathogen or abnormal protein are displayed on the surface of the cell in question, and are recognized by T-cells expressing receptors that specifically recognize those fragments. As shown in Figure 3.12, upon activation by antigen-binding, cytotoxic T-cells produce perforin, a molecule that will kill the cell by making holes in it. They also produce granzymes, molecules that trigger apoptosis in the target cell. Cytotoxic T-cells induce cell death very much like NK cells, but their action is much more specific because T-cells recognize their targets with the help of very specific receptors. Figure 3.13 shows the difference in function of the two types of T-cells, one that supports antibody formation in B cells (T-helper) and the other that triggers cell death (killer T) in abnormal cells such as those that are virally infected or cancerous [7].
The Role of Nanoparticles in Cancer Therapy through Apoptosis Induction
Published in Hala Gali-Muhtasib, Racha Chouaib, Nanoparticle Drug Delivery Systems for Cancer Treatment, 2020
Marveh Rahmati, Saeid Amanpour, Hadiseh Mohammadpour
When cells are infected by viruses, the perforin/granzyme apoptosis pathway is initiated by cytotoxic lymphocytes to remove the infected cells. Perforin, also known as cytoplasmic granule toxin, is a kind of protein with a pore-forming ability in mitochondrial membrane. Granzyme is a serine protease protein, which contains cytotoxic granules of cytotoxic lymphocytes (CLs). Although, Granzyme is required for triggering apoptosis, it should be delivered appropriately by perforin. In humans, there are numerous granzymes including A, B, H, K, and M, but the Granzymes A and B are the most abundant enzymes that are involved in apoptosis. This pathway is initiated when granzymes could enter into target cells. This internalization is facilitated by perforin. Granzyme B activates pro-apoptotic BH3-interacting domain death agonist Bid, leading to the activation of CASP-3. Activated CASP-3 is subsequently able to proceed with executive apoptosis. Granzyme B can also inactivate MCL-1, which is a member of the anti-apoptotic BCL-2 family [36]. The granzyme A pathway is also involved in apoptosis via activating a parallel, caspase-independent cell death pathway through single-stranded DNA damage [37].
Overview of Immune Tolerance Strategies
Published in Richard K. Burt, Alberto M. Marmont, Stem Cell Therapy for Autoimmune Disease, 2019
Charles J. Hackett, Helen Quill
The gene that encodes perforin, a molecule that functions in the lytic mechanism of cytotoxic T-cells and natural killer cells, has recently been implicated in a homeostatic function. A disease called familial hemophagocytic lymphohistiocytosis (FHL) is associated with a genetic defect in the perforin molecule.23 High levels of activated T cells in the blood and tissues of FHL patients lead to the overproduction of inflammation-producing factors, resulting in severe organ damage, especially of the liver, spleen, and central nervous system. Only bone marrow transplantation can successfully treat the approximately 80 children born in the United States each year with this immune disorder. Mutations in at least three different genes each can give rise to FHL. Patients with one type of FHL were lacking or had an inactive perforin molecule. As expected, the perforin-deficient FHL patients are defective in cytotoxic cell function, and presumably lack an important molecule needed to regulate cellular immune responses.
Anti-apoptotic effect of a static magnetic field in human cells that had been treated with sodium fluoride
Published in Journal of Environmental Science and Health, Part A, 2020
Magdalena Kimsa-Dudek, Agnieszka Synowiec-Wojtarowicz, Agata Krawczyk, Celina Kruszniewska-Rajs, Stanisław Gawron, Monika Paul-Samojedny, Joanna Gola
Apoptosis – programed cell death – plays a significance role in many processes, both physiological and pathological. Its function is to remove abnormal or damaged cells. This active process is regulated at many molecular levels and is fundamental to guaranteeing tissue homeostasis. In cells, it can be induced by three major pathways: the extrinsic (receptor), the intrinsic (mitochondrial) or the perforin/granzyme apoptosis pathway.[1] The course of apoptosis is strictly regulated and controlled by specific biochemical processes, which require the expression of many genes and which depends on several specific factors – above all on the pro- and anti-apoptotic proteins, including the Bcl-2 family proteins.[2] Programed cell death enables cells to be eliminated without causing any inflammation or damage to the surrounding tissues. However, disturbances in its course could lead to abnormalities in the functioning of cells and, consequently, to the development of diseases. It is believed that disturbances in the apoptosis process contribute to the development of cancer[3], neurodegenerative[4] and autoimmune diseases[5,6] and diseases of the cardiovascular system.[7]
Mathematical model for the in-host malaria dynamics subject to malaria vaccines
Published in Letters in Biomathematics, 2018
Titus Okello Orwa, Rachel Waema Mbogo, Livingstone Serwadda Luboobi
Due to intracellular infections, P. falciparum parasites are susceptible to immune-mediated control by CD8+ T cells, which target intracellular pathogens (Villarino, 2013). The CD8+ T cells have both direct and indirect effector pathways for parasite elimination at the liver stage. The indirect mechanism includes the production of IFN-γ and TNF, whereas the direct mechanism involves the release of perforin and granzymes (Nganou-Makamdop, van Gemert, Arens, Hermsen, & Sauerwein, 2012). IFN-γ suppresses parasite development through direct impairment of parasite differentiation in hepatocytes (Mellouk et al., 1987). Moreover, IFN-γ increases the expression of nitric oxide synthase which leads to subsequent increase in nitric oxide that confers protection against P. falciparum (Seguin et al., 1994). Although CD8+ T cells are sufficiently primed during blood stage malaria, they offer very minimal contribution to protective immunity. It is thought in Villarino (2013) that vascular endothelial cells that acquire antigen from IRBCs stimulate CD8+ T cells to release perforin and granzyme B during blood stage malaria. The capacity of CD8+ T cells to eradicate malaria parasites and infected cells both at the liver stage and at the blood stage is therefore considered in this paper.
Chelidonium majus crude extract induces activation of peripheral blood mononuclear cells and enhances their cytotoxic effect toward HeLa cells
Published in International Journal of Environmental Health Research, 2021
Ana Popovic, Milena Deljanin, Suzana Popovic, Danijela Todorovic, Predrag Djurdjevic, Sanja Matic, Milan Stankovic, Dusko Avramovic, Dejan Baskic
Double positive monocytes (DPMos) that express both CD4 and CD8 can also be detected in peripheral blood of healthy humans (Baba et al. 2006). In myosin-induced myocarditis in rats, Baba et al. (2008) showed a significant increase in the number of DPMos as prevailing infiltrating cells in cardiac lesions. These cells had a high expression of Fas ligand and cytotoxic factors such as perforin and granzyme B and exerted cytotoxic activity against tumor cells. Statistically significant increase in the ratio of monocytes double positive for CD4 and CD8 detected after CME treatment refers to the evolution of activated cells with enhanced cytotoxic potency.