Explore chapters and articles related to this topic
Putting a Cell Together
Published in Thomas M. Nordlund, Peter M. Hoffmann, Quantitative Understanding of Biosystems, 2019
Thomas M. Nordlund, Peter M. Hoffmann
T cells are white blood cells (lymphocytes) that play a central role in immunity. (“T” stands for thymus, where the T cells grow.) They are characterized by a special receptor on their cell surface called T cell receptors (TCRs) that interact with the major histocompatibility complex (MHC, a protein) on an antigen presenting cell (APC) that has managed to “bite off” a fragment of a foreign cell’s (or virus’s) protein or glycoprotein called an antigen (Figure 7.16). “Professional” APCs are cells that specialize in obtaining an antigen from an invading cell or virus and then displaying a fragment of the antigen, bound to an MHC molecule, on their membrane. The T cell recognizes and interacts with the MHC molecule complex on the membrane of the APC. (Note so far the T cell is not dealing directly with the invading cell.) When the T cell binds to the APC, the latter gives an additional signal that activates the T cell. The T cell then secretes a chemical (cytokine) that causes growth of more T cells, some of which become capable of killing the invading cell or cell that has been infected with virus. Huge amounts of biochemical and genetic information are known about the many components of this type of immune response, but we will focus on what takes place structurally when the T cell binds the MHC. For a more complete description of the immune recognition response, see K. Singleton et al.16 Read the Journal of Immunology for continuing, up-to-date coverage of discoveries about the immune response.
Coxiella burnetii as a Model Organism
Published in Raj Bawa, János Szebeni, Thomas J. Webster, Gerald F. Audette, Immune Aspects of Biopharmaceuticals and Nanomedicines, 2019
Erin J. van Schaik, Anthony E. Gregory, Gerald F. Audette, James E. Samuel
For gold NPs, the size of particles alone is enough to influence the degree of cellular uptake. Researchers measuring intracellular gold content within HeLa cells after incubating with a range of NP sizes (14–100 nm) found a 50 nm particle was optimal for cellular uptake [106]. The shape and surface charge of a NP also play a pivotal role in the interactions between APCs and NPs. By modifying NPs with different poly(amino acids)/proteins, lipids, or polymers to adjust the surface charge, intracellular uptake is markedly increased in a variety of different cell types [107–111]. In general, cationic particles are more readily internalized due to the anionic nature of cell membranes. Additionally, spherical particles are more readily endocytosed than rod-shaped particles, which the investigators suggested could be due to the curvature of the NP reducing the number of available receptor sites for binding [106, 112]. In order to facilitate antigen uptake into APCs further, NPs functionalized with ligands complementary to APC receptors can specifically target these cell types to induce the desired immune response. Some of the most common targets for this purpose include mannose receptors, Fc receptors, CD11c-CD18 integrins and MHC receptors [113–118]. In doing so, the efficacy and tolerance of these vaccines is significantly improved by increasing their uptake and minimizing some of the less desirable, heterologous effects of vaccination.
Active Targeting Strategies in Cancer with a Focus on Potential Nanotechnology Applications
Published in Mansoor M. Amiji, Nanotechnology for Cancer Therapy, 2006
Efficient, targeted delivery of gene therapy elements and/or antigens to antigen presentation cells (APC) has long been a goal for the induction of anti-cancer cell immune responses. Nanoparticles provide an exciting possibility to achieve this goal. Coating nanoparticles with mannan facilitates their uptake by APCs such as macrophages and dendritic cells that acts to target these materials to local-draining lymph nodes following their administration.76 Such an approach is likely to provide additional synergy in APC activation because polymer nanoparticles are efficiently phagocytosed by dendritic cells.77 Many APCs express LDL-type receptors, and molecules that interact with this class of receptors could be a means of targeting as well.78 Interestingly, LDL receptors can be an attractive targeting strategy for cancers because many tumors of different origins express elevated levels of this receptor.79 Therefore, LDL-based nanoparticles could be useful in targeting cancer.31
Polymer-based nano-therapies to combat COVID-19 related respiratory injury: progress, prospects, and challenges
Published in Journal of Biomaterials Science, Polymer Edition, 2021
From the history of vaccine development, it is well established that vaccination is one of the most effective strategies to prevent and control the spread of infectious diseases, where naturally developed immunity induces protective long-term immune memory in patients.[132] In general, vaccines introduce specific viral antigens on the cell surface of antigen-presenting cells (APCs), particularly dendritic cells, embodied in the major histocompatibility complex (MHC) I and II.[133] Such an event triggers the adaptive immune system by recognizing these antigens as invaders and induces antibodies production or T cells to eliminate these unwanted invaders. Consequently, memory B cells in the body develop virus-specific antibodies on its cell surface, which triggers a fast immune response to clear the similar viral infection in the future. There are three different generations of vaccine formulations currently used to trigger immune responses against infection, including live attenuated (whole inactivated pathogen) vaccines or first-generation vaccines, recombinant subunit vaccines (second-generation), and RNA/DNA vaccines or third-generation vaccines.[134,135] Since the outbreak of COVID-19, several different vaccine candidates have been developed and reached clinical phases due to a high urgency to halt the pandemic.[136]
Modelling combined virotherapy and immunotherapy: strengthening the antitumour immune response mediated by IL-12 and GM-CSF expression
Published in Letters in Biomathematics, 2018
Adrianne L. Jenner, Chae-Ok Yun, Arum Yoon, Adelle C. F. Coster, Peter S. Kim
Antigen presenting cells (APCs) include both dendritic cells and macrophages. These cells are stimulated by infected cells at a rate and decay at a rate . Helper T cells are then stimulated by APCs at a rate and decay at a rate . Both APCs and helper T cells then activate CTLs K at a rate and respectively. CTLs induce apoptosis in uninfected and infected tumour cells at a frequency-dependent rate with constant k. CTLs decay at a rate . We have assumed that initially there are no stimulated immune cells as these are only generated through the presence of virus infected tumour cells I.
IL-1α and IL-1β as alternative biomarkers for risk assessment and the prediction of skin sensitization potency
Published in Journal of Toxicology and Environmental Health, Part A, 2018
Min Kook Kim, Kyu-Bong Kim, Kyungsil Yoon, Sam Kacew, Hyung Sik Kim, Byung-Mu Lee
Keratinocytes are known to secrete cytokines including tumor necrosis factor alpha (TNF-α), interleukin (IL)-18, and interferon (IFN)-γ, in response to hapten sensitization and to stimulate DC and T cells (Roggen 2014). Dendritic cells play an important role in the process of skin sensitization through the capture of haptens and release of prostaglandin E2 (PGE2) and reactive oxygen species (ROS), both of which act as Toll-like receptor (TLR) ligands (Christensen and Haase 2012; Erkes and Selvan 2014). These ligands bind to TLR2 and TLR4 and activate the nuclear factor kappa beta (NF-κB) and mitogen-activated protein kinase (MAPK) pathways, which induce the expression of costimulatory molecules such as cluster of differentiation (CD)54, CD80, and CD86 on the cell surface, cytokines IL-1α, IL-1β, and TNF-α, and chemokines (Corsini et al. 2013; Kim et al. 2018; Lee and Kim 2018; Novak et al. 1999; Toebak et al. 2009). Therefore, DC function as antigen-presenting cells (APC) and induce T cell activity. Activated T cells induce ACD at hapten-exposed sites through proliferative and inflammatory responses (Banchereau and Steinman 1998); that is to say, skin sensitization is the consequence of immune responses by T cells. However, the use of DC obtained from the spleen and blood cells for testing of materials is limited owing to their low acquisition rates and high cost (Van Helden, Van Leeuwen, and Figdor 2008). In addition, a long time (typically 6–9 days) is required to induce the differentiation of DC precursors to DC (Van Helden, Van Leeuwen, and Figdor 2008). Further, experiments utilizing these primary cells demonstrated variations in expression of cytokines, cell surface molecules, and T cell activation (Van Helden, Van Leeuwen, and Figdor 2008). In contrast, RAW264.7 cells are known to play a role similar to that of DC in processing external antigens and are easy to culture (Van Helden, Van Leeuwen, and Figdor 2008). To circumvent the problems associated with DC, RAW264.7 cells were selected for our investigations.