Preclinical and Clinical Safety Assessment of Transdermal and Topical Dermatological Products
Tapash K. Ghosh in Dermal Drug Delivery, 2020
ACD reactions are induced by specificity antigens and are elicited by either specific antibodies from sensitized B lymphocytes (e.g., antibody-secreting plasma cells) or by sensitized T lymphocytes and macrophages in the case of cell-mediated immunity. Most contact sensitizers induce their reaction through antigenic stimulation in the form of a “hapten,” which is an incomplete antigen since it requires a suitable carrier molecule in order to become antigenic. If a drug is able to penetrate the skin and covalently bind with amino acids in the skin, dermal hypersensitivity is possible. If the hapten-protein conjugate is of a sufficiently large molecular size to be recognized as a foreign antigen, a specific antibody and/or specific cell-mediated immune response will ensue that sensitizes the skin immune system to the hapten molecule. Upon re-exposure of the skin to the sensitizing chemical, a dermal hypersensitivity reaction may be elicited. This inflammatory reaction is generally delayed-onset type IV hypersensitivity that stems from a cell-mediated immune response.
Physiology of the immune system
Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal in Principles of Physiology for the Anaesthetist, 2015
Type IV hypersensitivity (Figure 10.24) results from an antigen presentation to T lymphocytes causing a release of cytokines (IL-2, IL-4 and IFN-γ) that activate macrophages, with tissue injury. Reaction to Mycobacterium tuberculosis is a good example of type IV hypersensitivity. During infection, T cells recognize the antigen and proliferate, producing a population of sensitized T cells and the macrophages are activated. When these sensitized T cells are presented with the antigen by antigen-presenting cells, they release cytokines and the activated macrophages kill the microorganisms they contain. The lymphocytes and macrophages arise at least 24 hours after the provoking stimulus. With prolonged antigenic stimulation, the macrophages in the lesion fuse to form giant cells. A granuloma may form to wall off the infective focus, and within it extensive tissue damage leads to caseation with fibrosis and calcification.
Immunologically Mediated Diseases and Allergic Reactions
Julius P. Kreier in Infection, Resistance, and Immunity, 2022
Type IV hypersensitivity is also known as delayed hypersensitivity since the obvious signs of these reactions are observed twenty-four hours or more after contact with the antigen. In contrast to the first three types of hypersensitivity, which are antibody-mediated, type IV hypersensitivity reactions are cell-mediated immune responses involving T lymphocytes and activated macrophages (Figure 10.7). The most commonly recognized form of delayed hypersensitivity is allergic contact dermatitits, best exemplified by the acute eczema that develops following exposure to poison ivy. Other common allergens that induce allergic contact dermatitis include rubber, nickel, fragrances, cosmetics, and topical antibiotics. The contact dermatitis that may develop following exposure of a sensitized individual to bath soap is a typical form of DTH (Figure 10.8). More severe forms of DTH reactions have been observed in certain disease states such as leprosy or tuberculosis, where the antigen is persistent and cannot easily be eliminated by macrophages.
Physiological responses to cisplatin using a mouse hypersensitivity model
Published in Inhalation Toxicology, 2020
David M. Lehmann, Wanda C. Williams
Using a weight of the evidence approach, we arrived at the conclusion that CDDP exposure likely triggered a type I hypersensitivity reaction. However, the possibility remains that the effects we observed relate to other mechanisms. For example, the distinction between the different hypersensitivity classes is not always clear cut. Importantly, type IV reactions can occur in the lung triggering induction of airway hyperreactivity (Garssen et al. 1991). Although type IV reactions were traditionally aligned with Th1 cells, there are type IV hypersensitivity subtypes mediated by CD8+ and Th2 T-cells. When mediated by Th2 cells, a chronic asthma condition associated with eosinophil recruitment to the lung can develop (Czarnobilska et al. 2007). Importantly, we did not observe any signs of a skin irritation followed by repeated topical exposure to CDDP over a 15-day period. Still, additional investigations using this model and other approaches (e.g. T cell subset determinations) are necessary to better understand the contributions of different hypersensitivity types to CDDP hypersensitivity.
Computed tomography in hypersensitivity pneumonitis: main findings, differential diagnosis and pitfalls
Published in Expert Review of Respiratory Medicine, 2018
Olívia Meira Dias, Bruno Guedes Baldi, Francesca Pennati, Andrea Aliverti, Rodrigo Caruso Chate, Márcio Valente Yamada Sawamura, Carlos Roberto Ribeiro de Carvalho, André Luis Pereira de Albuquerque
The inhaled particle must have an aerodynamic diameter between 1 and 3 μm to reach the pulmonary acini, depositing in the terminal airways and alveoli. With continuous exposure, a type IV hypersensitivity response occurs. There is persistent and unrepaired epithelial cell damage with stimulation of interleukin (IL)-12 secretion by macrophages, thus promoting the differentiation of lymphocytes into a T-helper cell 1 (Th1)-like response. Immunocomplexes bind to Fc receptors on the surface of lymphocytes, stimulating the production of ILs, mainly tumor necrosis factor (TNF)-α and IL-1. These stimulate Th1 lymphocytes to produce interferon-γ. The latter further stimulates the production of TNF-α, transforming growth factor-β, and IL-1, generating a positive feedback mechanism that culminates in the chemoattraction of fibroblasts, increased local production of collagen, interstitial remodeling, and, finally, fibrosis. Some authors also postulated that the inability of the lymphocyte to eliminate a given antigen would polarize the immune response to Th2, resulting in a greater chance of disease progression to chronic HP with fibrosis [13,14].
Hypophysitis related to immune checkpoint inhibitors: An intriguing adverse event with many faces
Published in Expert Opinion on Biological Therapy, 2021
Maria V Deligiorgi, Charis Liapi, Dimitrios T Trafalis
The only, to date, available autopsy series reported by Cartrugelli et al suggests that the ir hypophysitis results from integration of inflammatory and autoimmune mechanisms triggered by binding of anti-CTLA-4 to CTLA-4 ectopically expressed on pituitary cells. This study suggested three pillars of the anti-CTLA-4-induced destruction of pituitary: (i) expression of CTLA-4 on pituitary endocrine cells mainly on gonadotropin-secreting and TSH-secreting cells; (ii) inflammatory type II hypersensitivity reactions triggered by immune complexes consisting of the CTLA-4 antibody administered therapeutically and the pituitary CTLA-4 antigen, which in turn destructs the pituitary cells and recruit macrophages and other inflammatory cells, responsible for phagocytosis and enhanced antigen presentation; (iii) autoimmune type IV hypersensitivity reactions involving tissue damage via production of cytokines, activation of B lymphocytes and phagocytes, and direct granzyme/perforin-mediated cytotoxicity. The inflammatory type II hypersensitivity reactions were recognized as early events followed by the autoimmune type IV hypersensitivity reactions [26].
Related Knowledge Centers
- Antibody
- Humoral Immunity
- Interleukin 12
- Mhc Class II
- Hypersensitivity
- Monocyte
- T Cell
- Macrophage
- Cell-Mediated Immunity
- Mhc Class II
- Antigen-Presenting Cell