Delayed allergic skin reactions to vaccines

Background: Recent advances in vaccination against the severe acute respiratory syndrome coronavirus 2 pandemic have brought allergists and dermatologists to the forefront because both immediate and delayed hypersensitivity reactions have been reported. Objective: This literature review focused on delayed reactions to vaccines, including possible causative agents and practical information on how to diagnose, evaluate with patch testing, and manage subsequent dose administration. Methods: Currently published reviews and case reports in PubMed, along with data on vaccines from the Centers for Disease Control and Prevention web site. Relevant case reports and reviews that focused on delayed reactions to vaccines were selected. Results: Most delayed hypersensitivity reactions to vaccines include cutaneous manifestations, which vary from local persistent pruritic nodules to systemic rashes. The onset is usually within a few days but can be delayed by weeks. Multiple excipients have been identified that have been implicated in delayed vaccine reactions, including thimerosal, formaldehyde, aluminum, antibiotics, and gelatin. Treatment with antihistamines, topical corticosteroids, or systemic corticosteroids alleviates symptoms in most patients. Such reactions are generally not contraindications to future vaccination. However, for more-severe reactions, patch testing for causative agents can be used to aid in diagnosis and approach further vaccination. Conclusion: Delayed-type hypersensitivity reactions to vaccines are not uncommon. If needed, patch testing can be used to confirm agents, including antibiotics, formaldehyde, thimerosal, and aluminum. In most cases, delayed cutaneous reactions are not contraindications to further vaccine administration.

Immunostimulant Activity of Marchantia paleacea Bertol. Herb Liverwort Ethanol Extract in BALB/c Mice

Immunostimulants are compounds that can stimulate an immune response by increasing the activity of non-specific and specific components of the immune system (humoral and cellular) against certain infections and diseases. The liverwort plant species Marchantia paleacea Bertol. has long been used as a source of nutrition and empirical medicine. However, scientifically there is still not much research data on immunomodulators in these plants. This study aims to determine the activity of immunomodulators in the ethanol extract of the herb Marchantia paleacea Bertol. in male mice of BALB/c strain. Bioactive compounds from this plant were extracted by maceration method using 96% ethanol. Extract characterization and phytochemical screening were determined according to WHO guidelines and standard procedures from previous studies. The immunomodulatory activity of the extract was tested by carbon clearance method and lymphoid organ index (non-specific responses), primary and secondary antibody titer tests (humoral specific responses), IL-2 cytokine levels and IFN-ɣ from serum secondary antibodies and delayed-type hypersensitivity reaction/DTH (cellular specific response). The results of qualitative phytochemical screening contained flavonoid compounds, saponins, phenolics, tannins and steroids/triterpenoids. The results of the non-specific immune response immunomodulator test showed that the dose of 52 mg/kg bw had the largest phagocytic index of 1.52 which included strong immunostimulation (K > 1.5) and the organ spleen index of 0.55 ± 0.11 which increased significantly compared to the control (p<0.05). The data on the acquisition of specific immune responses in the primary and secondary antibody titer test in the three test extracts resulted in increased titer levels compared to the control and at a dose of 52 mg/kg bw could significantly increase the levels of IL-2 cytokines in the control group (p<0,05). Meanwhile, in the DTH test, doses of 13 and 26 mg/kg bw could significantly increase the thickness of the soles of mice compared to controls (p<0.05).

Exposure to Deoxynivalenol During Pregnancy and Lactation Enhances Food Allergy and Reduces Vaccine Responsiveness in the Offspring in a Mouse Model

Deoxynivalenol (DON), a highly prevalent contaminant of grain-based products, is known to induce reproductive- and immunotoxicities. Considering the importance of immune development in early life, the present study investigated the effects of perinatal DON exposure on allergy development and vaccine responsiveness in the offspring. Pregnant mice received control or DON-contaminated diets (12.5 mg/kg diet) during pregnancy and lactation. After weaning, female offspring were sensitized to ovalbumin (OVA) by oral administration of OVA with cholera toxin (CT). Male offspring were injected with Influvac vaccine. OVA-specific acute allergic skin response (ASR) in females and vaccine-specific delayed-type hypersensitivity (DTH) in males were measured upon intradermal antigen challenge. Immune cell populations in spleen and antigen-specific plasma immunoglobulins were analyzed. In female CT+OVA-sensitized offspring of DON-exposed mothers ASR and OVA-specific plasma immunoglobulins were significantly higher, compared to the female offspring of control mothers. In vaccinated male offspring of DON-exposed mothers DTH and vaccine-specific antibody levels were significantly lower, compared to the male offspring of control mothers. In both models a significant reduction in regulatory T cells, Tbet+ Th1 cells and Th1-related cytokine production of the offspring of DON-exposed mothers was observed. In conclusion, early life dietary exposure to DON can adversely influence immune development in the offspring. Consequently, the immune system of the offspring may be skewed towards an imbalanced state, resulting in an increased allergic immune response to food allergens and a decreased immune response to vaccination against influenza virus in these models.

Cytokine expression in the delayed-type hypersensitivity response of Peromyscus yucatanicus infected by Leishmania (Leishmania) mexicana that healed spontaneously / Expressão de citocinas na resposta de hipersensibilidade de tipo retardado de Peromyscus yucatanicus infectado por Leishmania (Leishmania) mexicana que curou espontaneamente

Peromyscus yucatanicus tem sido empregado como modelo para estudar a leishmaniose tegumentar causada por Leishmania (Leishmania) mexicana. No entanto, não há informações sobre a cura espontânea e a resposta imune associada nesses roedores. O objetivo deste trabalho foi analisar a expressão de citocinas na resposta de hipersensibilidade do tipo retardado de Peromyscus yucatanicus infectado por Leishmania (Leishmania) mexicana que cicatrizou espontaneamente. Peromyscus yucatanicus (n = 40) foram inoculados com 2.5 × 106 parasitas na cauda e a evolução foi registrada semanalmente até o aparecimento das lesões ativas (Grupo I: não cicatrizadas) e até a cicatrização espontânea (Grupo II: cicatrizadas). Um grupo controle foi injetado com meio RPMI-1640. A resposta de hipersensibilidade do tipo retardado (DTH) e as expressões de citocinas (IFN-γ, IL-10, TNF) foram determinadas. A cura espontânea foi observada em 65% (13/20) dos P. yucatanicus do Grupo II. O grupo curado desenvolveu uma forte reação DTH que foi significativamente maior do que o grupo controle. Às 24 h, o IFN-γ foi altamente expresso na reação DTH de ambos os camundongos não curados e curados. IL-10 foi maior em camundongos curados em comparação com o grupo controle, enquanto a expressão de TNF foi maior em camundongos não curados. Em 48 h, INF-γ foi altamente expresso em camundongos não curados. A cicatrização espontânea de lesões cutâneas em P. yucatanicus foi associada à expressão de citocinas imunorreguladoras (IL-10) e efetoras (IFN-γ) na resposta DTH.

PATHOMORPHOLOGY OF EXPERIMENTAL INFECTION CAUSED BY DORMANT YERSINIA PSEUDOTUBERCULOSIS STRAINS

In the 2000s, with the development of scientific research on the uncultivated (dormant) state of pathogenic bacteria, the ideas about persistent, chronically recurrent infections, difficult to respond to antibiotic therapy have begun to shape. However, regarding human pseudotuberculosis (Far Eastern scarlet-like fever, FESLF), this question remains open. While analyzing the pathology of pseudotuberculosis, its clinical and epidemic manifestation as FESLF, we identified the etiopathogenetic prerequisites for the disease recurrence and development of persistent infection [3]. In this study, it was found that the strains of Yersinia pseudotuberculosis, which were in a dormant state, caused the development of a peculiar granulomatous inflammation in target organs with pronounced delayed-type hypersensitivity reactions in vivo. To reproduce the experimental infection, sexually mature white mice were inoculated with the strain 512 Y. pseudotuberculosis, serotype I sored for 10 years at the Museum of the Research Somov Institute of Epidemiology and Microbiology and transformed into a dormant state. For comparative studies, a dormant form from vegetative bacteria of the strain 512 Y. pseudotuberculosis was obtained by exposure to a large dose of kanamycin (the minimum antibiotic dose was exceeded 25 times). The infecting dose of both forms of bacteria was 108 µ/mouse. Samples of target organs (lung, liver, spleen) were collected for histological examination on days 3, 7, 10, 14, 21 and 32 after infection. Histological sections with 3-5 µm thickness were stained with hematoxylin and eosin according to standard techniques. It was established that strains of Y. pseudotuberculosis in dormant state caused in vivo development of a peculiar granulomatous inflammation due to delayed-type hypersensitivity reactions (DHR), which characterizes the protective reaction in infected host and reflects formation of local, tissue immunity in target organs. The peculiarities of granulomatous inflammation were revealed, in comparison with that of found during infection with vegetative ("wild") Y. pseudotuberculosis bacteria, namely: the granulomas were predominantly small in size, clearly delimited from the surrounding tissue, without destruction of central zone cells and formation of the so-called "granulomas with central karyorrhexis" (terminology proposed by A.P. Avtsyn) [4]; perivascular infiltrates and vasculitis consisted mainly of lymphocytes and often had a follicle-like appearance, resembling the follicles in lymphoid organs; in the lungs, a well-marked reaction of the bronchial-associated lymphoid tissue was observed, and in the spleen, a follicular hyperplasia, indicating a T-cell defense reaction, was observed. Thus, the causative agent of Y.pseudotuberculosis infection / FESLF, being in a dormant state, initiates the development of immunomorphological changes of a protective nature such as productive granulomatous inflammation with reactions of local tissue immunity in target organs and can contribute to the formation of persistent infection.

Alpha-Gal Syndrome: Involvement of Amblyomma americanum α-D-Galactosidase and β-1,4 Galactosyltransferase Enzymes in α-Gal Metabolism

Alpha-Gal Syndrome (AGS) is an IgE-mediated delayed-type hypersensitivity reaction to the oligosaccharide galactose-α-1, 3-galactose (α-gal) injected into humans from the lone-star tick (Amblyomma americanum) bite. Indeed, α-gal is discovered in salivary glands of lone-star tick; however, the tick’s specific intrinsic factors involved in endogenous α-gal production and presentation to host during hematophagy are poorly understood. This study aimed to investigate the functional role of two tick enzymes, α-D-galactosidase (ADGal) and β-1,4 galactosyltransferases (β-1,4GalT), in endogenous α-gal production, carbohydrate metabolism, and N-glycan profile in lone-star tick. The ADGal enzyme cleaves terminal α-galactose moieties from glycoproteins and glycolipids, whereas β-1,4GalT transfers α-galactose to a β1,4 terminal linkage acceptor sugars—GlcNAc, Glc, and Xyl—in various processes of glycoconjugate synthesis. An RNA interference approach was utilized to silence ADGal and β-1,4GalT in Am. americanum to examine their function in α-gal metabolism in tick and AGS onset. Silencing of ADGal led to the significant downregulation of genes involved in galactose metabolism and transport in Am. americanum. Immunoblot and N-glycan analysis of the Am. americanum salivary glands showed a significant reduction in α-gal levels in silenced tissues. However, there was no significant difference in the level of α-gal in β-1,4GalT-silenced tick salivary glands. A basophil-activation test showed a decrease in the frequency of activated basophil by ADGal-silenced salivary glands. These results provide an insight into the roles of ADGal and β-1,4GalT in α-gal production and presentation in ticks and the probable involvement in the onset of AGS.