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European Journal of Immunology Jun 2016Endocannabinoids are endogenous ligands for the cannabinoid (CB) receptors which include anandamide (AEA) and 2-arachidonyl glycerol (2-AG). 2-AG has been linked to...
Endocannabinoids are endogenous ligands for the cannabinoid (CB) receptors which include anandamide (AEA) and 2-arachidonyl glycerol (2-AG). 2-AG has been linked to inflammation due to its elevated expression in animal models of autoimmunity and hypersensitivity. However, administration of exogenous 2-AG has been shown to suppress inflammation making its precise role unclear. In the current study, we investigated the role of 2-AG following immunization of C57BL/6 (BL6) mice with methylated BSA (mBSA) antigen, which triggers both delayed-type hypersensitivity (DTH) and antibody response. We found that while naïve T cells and B cells expressed low levels of 2-AG, expression significantly increased upon activation. Furthermore, mBSA-immunized mice exhibited higher 2-AG concentration than naïve mice. Exogenous 2-AG treatment (40 mg/kg) in mBSA-immunized mice led to reduced DTH response, and decreased Th1 and Th17-associated cytokines including IL-6, IL-2, TNF-α, and the IgG response. Addition of 2-AG to activated popliteal lymph node (PopLN) cell cultures also inhibited lymphocyte proliferation. Together, these data show for the first time that activated T and B cells produce 2-AG, which plays a negative regulatory role to decrease DTH via inhibition of T-cell activation and proliferation. Moreover, these findings suggest that exogenous 2-AG treatment can be used therapeutically in Th1- or Th17-driven disease.
Topics: Animals; Arachidonic Acids; B-Lymphocytes; Cytokines; Endocannabinoids; Female; Glycerides; Hypersensitivity, Delayed; Immunomodulation; Lymphocyte Activation; Mice; Receptors, Cannabinoid; T-Lymphocytes
PubMed: 27064137
DOI: 10.1002/eji.201546181 -
Journal of Primary Care & Community... 2021The term "COVID arm" has been coined to describe a harmless delayed hypersensitivity reaction occurring approximately a week after administration of the novel SARS-CoV-2...
The term "COVID arm" has been coined to describe a harmless delayed hypersensitivity reaction occurring approximately a week after administration of the novel SARS-CoV-2 mRNA vaccine. It appears as a red, warm, pruritic, indurated, or swollen area in the vicinity of the vaccine site. These reactions, especially if accompanied by systemic symptoms, have been mistaken for cellulitis. We report 3 cases of COVID arm, 2 of which were mistaken for cellulitis. Distinguishing features of COVID arm from cellulitis include pruritus as a common finding, occurrence approximately a week after vaccination, a lack of progression of symptoms, rapid response to topical steroids, and/or spontaneous resolution usually over 4 to 5 days.Practice Points:• Patients receiving SARS-CoV-2 vaccines may experience delayed hypersensitivity reactions characterized by erythema, swelling, and itching occurring near the vaccination site (COVID arm), approximately a week after vaccination.• Clinicians can distinguish SARS-CoV-2 vaccine reactions from cellulitis by the time of onset (approximately a week vs 5 days), by the lack of progression of symptoms, and resolution over 4 to 5 days.• Severe cases of COVID arm may be treated with topical steroids.
Topics: Arm; COVID-19; COVID-19 Vaccines; Cellulitis; Diagnostic Errors; Humans; Hypersensitivity, Delayed; SARS-CoV-2; Vaccines
PubMed: 34120504
DOI: 10.1177/21501327211024431 -
Immunology Sep 19671. Guinea-pigs injected with testis autoclavate (WT) in incomplete adjuvant develop antibody but no delayed hypersensitivity or testicular lesions. These animals fail to...
1. Guinea-pigs injected with testis autoclavate (WT) in incomplete adjuvant develop antibody but no delayed hypersensitivity or testicular lesions. These animals fail to develop delayed hypersensitivity or a lesion when subsequently injected with antigen in complete adjuvant. Animals similarly treated, and then given repeated injection of immune cells from animals treated with whole testis and complete adjuvant, develop both delayed hypersensitivity and the characteristic orchitis. 2. Guinea-pigs injected with a purified fraction (designated H) with incomplete adjuvant fail to develop either circulating antibody, delayed hypersensitivity or a testicular lesion. Animals subsequently injected with this antigen and complete adjuvant, develop delayed hypersensitivity but no circulating antibody or testicular lesion. Three of the five animals similarly treated and given repeated injections of serum containing anti-testis antibody also develop orchitis. 3. A sequential study of fourteen animals killed at daily intervals after they were injected with WT and complete adjuvant, showed that antibody was first detected in the testis on the same day as delayed hypersensitivity first appeared. Circulating antibody was not detected until 2 days later. The specific testicular antigen showed first signs of disappearing on the 10th day, by which time histological evidence of orchitis was first detected. 4. Antibody was not detected in the testes in any animal in the absence of delayed hypersensitivity.
Topics: Adjuvants, Immunologic; Animals; Antibody Formation; Antigen-Antibody Reactions; Fluorescent Antibody Technique; Guinea Pigs; Hypersensitivity, Delayed; Immunization; Lymph Nodes; Male; Orchitis; Skin Tests; Spleen; Testis
PubMed: 4861495
DOI: No ID Found -
Clinical and Experimental Dermatology Jan 2022Several individuals have developed delayed localized cutaneous vaccine reactions to the two novel mRNA Covid-19 vaccines. Clinical and histopathologic results of this...
Several individuals have developed delayed localized cutaneous vaccine reactions to the two novel mRNA Covid-19 vaccines. Clinical and histopathologic results of this case series study confirm that the localized injection-site reactions to the mRNA COVID-19 vaccines are delayed hypersensitivity reactions that, unlike immediate hypersensitivity reactions, are not a contraindication to vaccination.
Topics: 2019-nCoV Vaccine mRNA-1273; Adult; Aged; Aged, 80 and over; COVID-19; Drug Hypersensitivity; Female; Humans; Hypersensitivity, Delayed; Injection Site Reaction; Male; Middle Aged; Retrospective Studies; SARS-CoV-2
PubMed: 34288056
DOI: 10.1111/ced.14856 -
PloS One 2012Hypersensitivity diseases are associated with many severe human illnesses, including leprosy and tuberculosis. Emerging evidence suggests that the pathogenesis and...
BACKGROUND
Hypersensitivity diseases are associated with many severe human illnesses, including leprosy and tuberculosis. Emerging evidence suggests that the pathogenesis and pathological mechanisms of treating these diseases may be attributable to sphingolipid metabolism.
METHODS
High performance liquid chromatography-tandem mass spectrometry was employed to target and measure 43 core sphingolipids in the plasma, kidneys, livers and spleens of BALB/c mice from four experimental groups: control, delayed-type hypersensitivity (DTH) model, DTH+triptolide, and control+triptolide. Orthogonal partial least squares discriminant analysis (OPLS-DA) was used to identify potential biomarkers associated with variance between groups. Relationships between the identified biomarkers and disease markers were evaluated by Spearman correlation.
RESULTS
As a treatment to hypersensitivity disease, triptolide significantly inhibit the ear swelling and recover the reduction of splenic index caused by DTH. The sphingolipidomic result revealed marked alterations in sphingolipid levels between groups that were associated with the effects of the disease and triptolide treatment. Based on this data, 23 potential biomarkers were identified by OPLS-DA, and seven of these biomarkers correlated markedly with the disease markers (p<0.05) by Spearman correlation.
CONCLUSIONS
These data indicate that differences in sphingolipid levels in plasma and tissues are related to DTH and treatment with triptolide. Restoration of proper sphingolipid levels may attribute to the therapeutic effect of triptolide treatment. Furthermore, these findings demonstrate that targeted sphingolipidomic analysis followed by multivariate analysis presents a novel strategy for the identification of biomarkers in biological samples.
Topics: Animals; Biomarkers; Chromatography, High Pressure Liquid; Dinitrofluorobenzene; Disease Progression; Diterpenes; Ear; Epoxy Compounds; Hypersensitivity, Delayed; Kidney; Male; Mice; Mice, Inbred BALB C; Phenanthrenes; Sphingolipids; Spleen; Tandem Mass Spectrometry; Treatment Outcome
PubMed: 23300675
DOI: 10.1371/journal.pone.0052454 -
Archives of Disease in Childhood Nov 1983The clinical patterns of adverse reactions to cows' milk were examined in 72 children with cows' milk hypersensitivity. Two main groups were found, according to the time...
The clinical patterns of adverse reactions to cows' milk were examined in 72 children with cows' milk hypersensitivity. Two main groups were found, according to the time of onset of the adverse reaction--immediate onset, within one hour of milk ingestion and delayed onset, after one hour. Children with immediate onset reactions usually had cutaneous manifestations, positive prick tests, raised IgE values, were atopic, and the reaction was provoked by only small amounts of milk. Children with delayed onset reactions usually had gastrointestinal manifestations; negative prick tests; normal IgE values; were not atopic; had a history of vomiting, diarrhoea, and colic in the first year of life; and a larger amount of milk was needed to provoke the adverse reaction. Placing affected children into one or other category should increase the reliability of interpreting milk prick tests and clinical findings.
Topics: Animals; Cattle; Child; Child, Preschool; Female; Food Hypersensitivity; Gastrointestinal Diseases; Humans; Hypersensitivity, Delayed; Hypersensitivity, Immediate; Immunoglobulin E; Infant; Milk; Skin Diseases; Skin Tests; Time Factors
PubMed: 6651320
DOI: 10.1136/adc.58.11.856 -
Proceedings of the National Academy of... Jul 1973Genetic control of the response to specific natural-product antigens has been documented in three informative families. Families were selected on the basis of probands...
Genetic control of the response to specific natural-product antigens has been documented in three informative families. Families were selected on the basis of probands with tuberculosarcoidosis, chronic cutaneous moniliasis, and rheumatoid arthritis. An increased incidence of delayed cutaneous unresponsiveness was observed in each family. Positive associations were identified between HL-A haplotypes and immediate cutaneous hypersensitivity responses to 5, 8, and 11 of 23 test antigens in the three respective families. HL-A-associated differences in averaged responses of cutaneous hypersensitivity were excluded. These significant associations are consistent with linkage between HL-A haplotypes and genes responsible for the immune response to various natural-product antigens.
Topics: Antigens; Antigens, Bacterial; Arthritis, Rheumatoid; Candidiasis, Cutaneous; Chronic Disease; Female; Genetic Linkage; Histocompatibility Antigens; Humans; Hypersensitivity, Delayed; Male; Phenotype; Sarcoidosis; Skin Tests
PubMed: 4516211
DOI: 10.1073/pnas.70.7.2157 -
Journal of Investigational Allergology... 2013Nonimmediate drug hypersensitivity reactions (DHRs) are difficult to manage in daily clinical practice, mainly owing to their heterogeneous clinical manifestations and... (Review)
Review
Nonimmediate drug hypersensitivity reactions (DHRs) are difficult to manage in daily clinical practice, mainly owing to their heterogeneous clinical manifestations and the lack of selective biological markers. In vitro methods are necessaryto establish a diagnosis, especially given the low sensitivity of skin tests and the inherent risks of drug provocation testing. In vitro evaluation of nonimmediate DHRs must include approaches that can be applied during the different phases of the reaction. During the acute phase, monitoring markers in both skin and peripheral blood helps to discriminate between immediate and nonimmediate DHRs with cutaneous responses and to distinguish between reactions that, although they present similar clinical symptoms, are produced by different immunological mechanisms and therefore have a different treatment and prognosis. During the resolution phase, in vitro testing is used to detect the response of T cells to drug stimulation; however, this approach has certain limitations, such as the lack of validated studies assessing sensitivity. Moreover, in vitro tests indicate an immune response that is not always related to a DHR. In this review, members of the Immunology and Drug Allergy Committee of the Spanish Society of Allergy and Clinical Immunology (SEAIC) provide an overview of the most widely used in vitro tests for evaluating nonimmediate DHRs.
Topics: Antigen-Antibody Complex; Antigens, CD; Antigens, Differentiation, T-Lymphocyte; Biomarkers; Drug Hypersensitivity; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Humans; Hypersensitivity, Delayed; Immunoglobulin E; Lectins, C-Type; Lymphocyte Activation; Real-Time Polymerase Chain Reaction; Skin; Skin Tests; T-Lymphocytes
PubMed: 23964550
DOI: No ID Found -
Dermatology Online Journal May 1999Although the delayed type hypersensitivity (DTH) reaction was discovered over 100 years ago, the exact nature of the reaction has been the subject of contentious debate... (Review)
Review
Although the delayed type hypersensitivity (DTH) reaction was discovered over 100 years ago, the exact nature of the reaction has been the subject of contentious debate over the years. The reaction was discovered in 1882 by Robert Koch, but it was not until the 1940s that Landsteiner and Chase proved that the reaction was mediated by the cellular and not the humoral arm of the immune system. The first DTH reaction described used only the tuberculin antigen (tuberculin reaction), but the definition was later expanded to include cell mediated reactions to other bacterial and viral antigens, responses to pure protein with adjuvant or haptens, and host responses to allograft. The DTH skin test is used to test if prior exposure to an antigen has occurred. When small quantities of antigen are injected dermally, a hallmark response is elicited which includes induration, swelling and monocytic infiltration into the site of the lesion within 24 to 72 hours. This reaction has been shown to be absolutely dependent on the presence of memory T cells. Both the CD4+ and CD8+ fractions of cells have been shown to modulate a response. Contemporary debate regarding the reaction is focused on the role of the Th1 and Th2 cells originally discovered by Mosmann. It has been postulated that the Th1 cell is the "inducer" of a DTH response since it secretes interferon gamma (IFN ), a potent stimulator of macrophages, while the Th2 cell is either not involved or acting as a downregulator of the cell mediated immune response. Despite the early experimental success of this theory, experiments have shown that Th2 cells may be involved in certain types of proinflammatory cell mediated immunity. This review focuses on the nature of the different forms of DTH that can be elicited and the different experimental evidence that has led to the current theories regarding DTH and its role in cell mediated immunity.
Topics: Antigen-Presenting Cells; Graft vs Host Disease; History, 20th Century; Humans; Hypersensitivity, Delayed; Immunity, Cellular; T-Lymphocytes
PubMed: 10673450
DOI: No ID Found -
Annals of Surgery Sep 1977Primary failure of host defense mechanisms has been associated with increased infection and mortality. Anergy, the failure of delayed hypersensitivity response, has been...
Primary failure of host defense mechanisms has been associated with increased infection and mortality. Anergy, the failure of delayed hypersensitivity response, has been shown to identify surgical patients at increased risk for sepsis and related mortality. The anergic and relatively anergic patients whose skin tests failed to improve had a mortality rate of 74.4%, whereas those who improved their responses had a mortality rate of 5.1% (P < 0.001). This study documents abnormalities of neutrophil chemotaxis, T-lymphocyte rosetting in anergic patients and the effect of autologous serum. These abnormalities may account for the increased infection and mortality rates in anergic patients. Skin testing with five standard antigens has identified 110 anergic (A) or relatively anergic (RA) patients in whom neutrophil chemotaxis (CTX) and bactericidal function (NBF), T-lymphocyte rosettes, mixed lymphocyte culture (MLC), cell-mediated lympholysis (CML), and blastogenic factor (BF) were studied. The MLC, CML and BF were normal in the patients studied, and were not clinically helpful. Neutrophil CTX in 19 controls was 117.5 +/- 1.6 u whereas in 40 A patients, neutrophils migrated 81.7 +/- 2.3 u and in 15 RA patients 97.2 +/- 3.8 u (P < 0.01). In 14 patients whose skin tests converted to normal, neutrophil migration improved from 78.2 +/- 5.4 u to 107.2 +/- 4.0 u (P < 0.01). Incubation of A or control neutrophils in A serum reduced migration in A patients from 93 +/- 3.7 u to 86.2 +/- 3.5 u (P < 0.01) and in normals from 121.2 +/- 1.6 u to 103.6 +/- 2.6 u (P < 0.001). The per cent rosette forming cells in 66 A patients was 42.5 +/- 3.1 compared to 53.6 +/- 2.8 in normal responders (P < 0.02). Incubation of normal lymphocytes in anergic serum further reduced rosetting by 30%. Restoration of delayed hypersensitivity responses and concurrent improvement in cellular and serum components of host defense were correlated with maintenance of adequate nutrition and aggressive surgical drainage.
Topics: Adolescent; Adult; Aged; Chemotaxis, Leukocyte; Humans; Hypersensitivity, Delayed; Infections; Lymphocyte Culture Test, Mixed; Middle Aged; Neutrophils; T-Lymphocytes; Wounds and Injuries
PubMed: 142452
DOI: 10.1097/00000658-197709000-00002