China
Africa
Explore chapters and articles related to this topic
Acquired Immunity
Published in Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal, Principles of Physiology for the Anaesthetist, 2020
Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal
Several interactions between antigen and T-cell receptor must take place for T-cell activation. The antigen must be presented to the T cell as a peptide fragment within a groove of the MHC molecules on the APCs. The T cell receptor only recognizes the foreign protein together with self MHC. The combination of TCR, MHC molecule and antigen fragment (peptide) is known as trimolecular complex.
Delivery of Immune Checkpoint Inhibitors Using Nanoparticles
Published in Hala Gali-Muhtasib, Racha Chouaib, Nanoparticle Drug Delivery Systems for Cancer Treatment, 2020
Abdullah Shaito, Houssein Hajj Hassan
A single signal is not enough for T cell activation; a T cell is not activated when the TCR (T cell receptor) binds an antigen-bound MHCI complex. T cell activation requires an additional signal viz. the binding of co-receptors. This second signal has been termed co-stimulation. In T cells, the second signal takes place when CD28 present on T cells binds to CD86 (B7-2) or CD80 (B7-1) expressed by APCs [16–18]. These co-receptors or co-stimulants, when active, act as accelerators that promote the T cell activation and, hence, the immune response. However, it was later discovered that some co-receptors act, in fact, as brakes that reduce the activation of T cells. These brake co-receptors are required, as mentioned above, to avoid an exaggerated and damaging immune response. The brakes inhibitory signaling pathways, are termed the immune checkpoints, and constitute any signal that inhibit priming of T cell activation or any signal that reduce an already initiated T cell response [19].
Immunologic Tolerance
Published in Constantin A. Bona, Francisco A. Bonilla, Textbook of Immunology, 2019
Constantin A. Bona, Francisco A. Bonilla
A pair of surface ligands important in co-stimulation are T cell CD28 and B7 (CD80) on the surface of APCs (dendritic cells, activated macrophages and activated B cells). Monovalent (Fab) antibodies to CD28 or B7 induce anergy in TH1 cells. Bivalent antibodies to CD28 can overcome the anergy induced by fixed APC described above. Some have hypothesized that resting B cells may be a predominant source of defective antigen presentation in the induction of T cell anergy and self tolerance. Resting B cells do not express co-stimulatory molecules such as B7, which is expressed only after activation, and B cells far outnumber other MHC class II+, co-stimulation-defective cells in lymphoid tissues. MHC class-II+ T cells are also unable to provide co-stimulation and may induce anergy in cells which recognize the combinations of peptide and MHC on their surface. Additional co-stimulation molecules whose participation, or lack thereof, in cellular interactions may influence anergy induction include CD2 and CD58 (LFA-3), and CD11a/CD18 (LFA-1) and CD54 (ICAM-1). (See Chapter 6 for a detailed discussion of co-stimulation in T cell activation.)
Current status in cellular-based therapies for prevention and treatment of COVID-19
Published in Critical Reviews in Clinical Laboratory Sciences, 2023
Dima Hattab, Mumen F. A. Amer, Amirah Mohd Gazzali, Lay Hong Chuah, Athirah Bakhtiar
Highly activated and fully functional CD4+ and CD8+ T cells are usually pronounced within two weeks of the onset of symptoms in SARS-CoV-2-infected patients. One study revealed that COVID-19 patients exhibited main memory SARS-CoV-2-targeted CD4+ phenotypes, producing Th1 cytokines, and SARS-CoV-2-specific CD8+, expressing high levels of perforin and demonstrating effector effects [51]. In another study, CD38- and human leukocyte antigen (HLA)-DR-expressing memory CD4+ and CD8+ T cells, CD4+ PD-1+ memory T cells, highly proliferative Ki76+, and non-naïve CD4+ and CD8+ T cells were found to be more pronounced in patients with severe infection [52]. Excessive T cell activation results in either compromised or exaggerated T cell response. Compared to healthy individuals, dysregulation of T cell subsets was also apparent in SARS-CoV-2-infected patients. COVID-19 patients exhibited lower levels of naïve and central memory CD8+ T cells, comparable levels of the naïve, central memory, and effector CD4+ T cells, and higher levels of the terminally differentiated effector CD4+ and CD8+ T cells [47]. The regulatory T cell (Treg) phenotypes are more pronounced in mild COVID-19 cases.
A Review of Immunomodulatory Effects of Fluoroquinolones
Published in Immunological Investigations, 2021
Shokrollah Assar, Reza Nosratabadi, Hossein Khorramdel Azad, Javad Masoumi, Mahshad Mohamadi, Gholamhossein Hassanshahi
It has been documented that the immunomodulatory effects of FQs are exerted on Th cells, as ciprofloxacin induces an immunomodulatory stress response in human T lymphocytes (Fukumoto et al. 2013). These cells play a fundamental role in humoral and cellular immunity, and the nature of the immune responses is determined by some effector Th cells (Th1, Th2, Th9, Th17, and Th22), which are differentiated from the naïve T cells following antigenic stimulation (Mosmann and Sad 1996). The processes of differentiation in various types of effector T cells are completely associated with the presence of particular cytokines in the T cell microenvironment. IL-4 induces Th2 cell differentiation, which results in B cell activation and potentiates humoral immunity; in contrast, IFN-γ stimulates Th1 cell differentiation, which promotes the expression of Th1-cytokines (IFN-γ, IL-2, and TNF-α) (O’Garra and Arai 2000; Rengarajan et al. 2000). The concentration and magnitude of the produced cytokines in response to infections result in T cell activation, thereby leading to infection clearance.
New nonchemotherapy treatment options for cutaneous T-cell lymphomas
Published in Expert Review of Anticancer Therapy, 2021
In chimeric antigen receptor T cells (CAR T-cell) therapy, T cells from the patient or donor are genetically engineered to become activated and to induce a cytotoxic response against targeted tumor cells[60]. To generate CAR T cells, leukapheresed T cells are activated in vitro and incubated with genetically engineered CAR-encoding viral vectors. The vectors promote CAR RNA entry into the cell, where it is then reverse transcribed and incorporated into the genome of the T cells. The encoded receptor allows the T cells to recognize a specified surface antigen and initiate T cell activation, proliferation, and memory independent of T cell receptor (TCR) activity[61]. The transfected T cells then undergo ex vivo expansion before being reinfused into the patient. There are currently two CAR T-cell therapies approved for hematologic indications: axicabtagene ciloleucel for relapsed/refractory large B-cell lymphomas (LBCL) and tisagenlecleucel for both relapsed/refractory B-cell acute lymphoblastic leukemia and LBCL[62,63].