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The Challenge of Parasite Control
Published in Eric S. Loker, Bruce V. Hofkin, Parasitology, 2023
Eric S. Loker, Bruce V. Hofkin
Other issues can hamstring the development of effective vaccines. One concern is the route through which a vaccine is administered. To effectively stimulate a protective immune response, the key antigenic peptides in the vaccine must be presented to CD4+ T cells by antigen-presenting cells. Because of the need to prevent proteolysis of the antigens before they reach the antigen-presenting cells, many vaccines are given by injection rather than orally to avoid the low pH of the stomach and proteases found there. Vaccine administration via injection may not be of concern if the vaccine is designed to protect against a pathogen normally found in the blood or the lymphatic fluid. For other parasites, such as those inhabiting the intestinal lumen or the lungs, this route of administration may reduce vaccine efficacy because it does not produce the necessary mucosal immunity. Ideally, a vaccine will mimic a normal infection as closely as possible and inducing immunity at the normal portal of entry for the parasite is an important consideration.
In vitro Testing for Adverse Drug Reactions
Published in Kirsti Kauppinen, Kristiina Alanko, Matti Hannuksela, Howard Maibach, Skin Reactions to Drugs, 2020
Brender et al.16 have studied the T-lymphocyte responses in penicillin allergy in a more detailed fashion. The data indicated a heterogeneous response. The response could be elicited with both penicillin G itself and penicillin G coupled with human serum albumin. Both CD4 and CD8 T-cells were stimulated with penicillin G, but only CD4 T-cells with the albumin-coupled drug. The penicillin G-speeific clones were human leukocyte antigen (HLA) class I or class II restricted and the albumin-coupled drug had to undergo antigen processing prior to antigen presentation. Various cell types could serve as antigen presenting cells. The cytokine pattern secreted was also heterogeneous, most T-cell clones producing large amounts of interleukin-2, interferon-gamma, and tumor necrosis factor-alpha, and variable amounts of interleukin-4 and -5. The immunological heterogeneity may explain the variety of clinical pictures in penicillin allergy.
Dermal Hypersensitivity: Immunologic Principles and Current Methods of Assessment
Published in David W. Hobson, Dermal and Ocular Toxicology, 2020
The two major arms of the immune system are humoral immunity and cell-mediated immunity. Specific antibodies from B lymphocytes mediate humoral immunity, whereas specifically sensitized T lymphocytes produce cell-mediated immunity. Various cells (macrophages) in the mononuclear phagocytic system (MPS) process and present antigens on their surface membranes in context with class II major histocompatibility (MHC) antigens. These antigen-presenting cells enable specific lymphocytes to recognize the foreign antigen and to generate an immune response against the antigenic substance. The cell in the skin with this antigen presentation role is primarily the Langerhans’ cell.25 T lymphocytes function as two main subpopulations which express different surface markers, the helper/effector T cells (TH) and the suppressor T cells (Ts). Human TH cells express CD4+ and Ts cells express CD8+ surface antigens.17
TRYBE®: an Fc-free antibody format with three monovalent targeting arms engineered for long in vivo half-life
Published in mAbs, 2023
Emma Davé, Oliver Durrant, Neha Dhami, Joanne Compson, Janice Broadbridge, Sophie Archer, Asher Maroof, Kevin Whale, Karelle Menochet, Pierre Bonnaillie, Emily Barry, Gavin Wild, Claude Peerboom, Pallavi Bhatta, Mark Ellis, Matthew Hinchliffe, David P. Humphreys, Sam P. Heywood
The TrYbe® format was specifically conceived to facilitate monovalent target binding in an Fc-free molecule. The value of this was highlighted when targeting multivalent antigens such as TNF and IL-17A. TrYbes® formed vastly smaller antibody-antigen complexes in vitro compared to comparator bivalent, bispecific IgG-based formats. The formation of small immune complexes is a natural consequence of antibody-antigen engagement in clinical settings. However, potentially serious issues such as immunogenicity or immune complex disorders have been reported, the former due to clearance via antigen presenting cells and the latter arising from unsuccessful clearance of immune complexes from circulation and their subsequent deposition in tissues and organs.11,82,83 These disorders can be aggravated by Fc-containing complexes and aberrant activation of Fc effector functionalities including complement activation. Our studies support previous reports,10,11 which conclude that both antigen and antibody valency, and the ratio of antigen to antibody are important factors that contribute to the formation of these complexes in vitro. This was shown to be further complicated when considered in the context of bispecific targeting and underlies the importance to carefully consider not only the mode of action of the antibody but also properties of the targeted antigens along with the design of the therapeutic molecule. By being monovalent and Fc-free, the TrYbe® is favorably placed in this context to minimize potential risks.
Current perspectives on the diagnosis, assessment, and management of vasculitic neuropathy
Published in Expert Review of Neurotherapeutics, 2022
Yuki Fukami, Haruki Koike, Masahisa Katsuno
Although our understanding of the initial pathogenesis in specific vasculitis is still incomplete, two major pathways leading to vasculitis are humoral and cell-mediated immunity [9–12]. Immune complex deposition within the vessel walls can cause complement activation and release of proinflammatory cytokines from endothelial cells [12]. Persistent inflammation within the vessel wall causes vascular injury. Immune complex-mediated injury is relevant to the pathophysiology of IgA, hypocomplementemic urticarial, and cryoglobulinemic vasculitis [5]. Cell-mediated immunity requires that antigen-presenting cells present relevant antigens to circulating T cells. These interactions result in the production of inflammatory cytokines, cell adhesion molecules, and other inflammatory mediators from inflammatory and endothelial cells leading neutrophils and lymphocytes to adhere to and injure blood vessels [12]. In turn, vascular inflammation results in the occlusion of the vessels’ lumen, leading to ischemia in regions supplied by the affected vessels [2].
Axicabtagene ciloleucel for the treatment of relapsed or refractory follicular lymphoma
Published in Expert Review of Anticancer Therapy, 2022
CD4+ and CD8 + T-cells are predominantly responsible for the process of immunosurveillance of cancer cells. A hallmark of tumorigenesis is immunoediting, a process of tumor cell selection by the immune system for clones capable of escaping immune pressure. Immune escape includes genetic and epigenetic changes that result in (1) alterations in tumor antigen expression, (2) production of factors that negatively regulate T-cells, (3) changes to the tumor microenvironment to upregulate immune cells such as regulatory T-cells and myeloid-derived suppressor cells and (4) downregulation of MHC molecules [45–47]. CD8+ and CD4+ lymphocytes require MHC class I and II, respectively, to recognize tumor antigens in the same fashion as they would foreign peptides by antigen presenting cells.