Red meat allergy induced by tick bites: A Norwegian case report.

SUMMARY: Food allergies, especially delayed hypersensitivity reactions, are often challenging for both patients and clinicians. Here, we report the case of a 64-year-old man who had allergic reactions six hours after eating a meal containing red meat. He reported that he had several tick bites in months before the reaction. High serum specific IgE levels of alpha-gal confirmed the diagnosis of alpha-gal allergic reaction with delayed onset after red meat ingestion caused by tick bite.

Carissa congesta Wight and Benincasa hispida (Thunb.) Cogn. as budding immunomodulatory agents.

Carissa congesta and Benincasa hispida are well-known medicinally important plants associated with diabetes, inflammation, protozal infections and cancer. Here, we emphasized up on the immunomodulatory potential of these plants as the source of lupeol, P-sitosterol and ursolic acid. Petroleum ether extracts of C. congesta roots and B. hispida seeds were subjected to acute toxicity studies. They were screened for its immunomodulatory prospective in rats by Haemagglutination Antibody (HA) titre and Delayed-Type Hypersensitivity (DTH) response using Sheep Red Blood Cells (SRBCs of-0.5x109) as antigens. Carbon Clearance test (Phagocytic Index) was estimated by Indian ink suspension. Complete Freund's Adjuvant (CFA) induced arthritis model interpretation was done by paw edema, kene joint erosion (transverse section), body weights, arthritic index and biochemical levels (RBC, WBC and Hb levels). Both the extracts were found to be therapeutically safe up to 5000 mg/kg. Dosage of 100 mg/kg was not satisfactory; and 500 and 250 mg/kg showed significant immunostimmulation (HA Titre) and immunosuppression (DTH response, 48 h). Benincasa hispida seed and Carissa congesta root extracts showed phagocytic Index of 0.0163±0.003, 0.0145±0.003 and 0.0183±0.003, 0.0176±0.003 at 250 mg/kg and 500 mg/kg, respectively. CFA model revealed that the B. hispida seed and C. congesta root extracts decreased paw volume, knee joint erosion, increased body weights and biochemical parameters with an arthritic index of 1.31±0.12, 1.44±0.15 and 1. 16±0.09, 1.36±0.13 at 250 mg/kg and 500 mg, respectively. The results were interpreted by One- way ANOVA followed by Dunnett test. Extracts showed relevance as promising immunostimulators as compared to control.

An unusual case of delayed-type hypersensitivity to ceftriaxone and meropenem.

Recent studies have demonstrated a low cross-reactivity between ß-lactam antibiotics and carbapenems in IgE-mediated reactions. There are no studies on cross-reactivity of meropenem in patients with non-immediate hypersensitivity to cephalosporins. We describe a case of a 13-year-old male, admitted in Neurosurgery with a severe extradural empyema complicating frontal sinusitis, submitted to an emergent bifrontal craniotomy. A generalized maculopapular exanthema, fever and malaise, appeared by the 7th day of meningeal doses of ceftriaxone, clindamycin and vancomycin. Those were replaced by meropenem, with posterior worsening of the reaction and mucosal involvement. A new scheme with amikacin, metronidazole and linezolid was done with improvement. Skin prick, intradermal and patch tests to penicillins, ceftriaxone and meropenem were negative. Lymphocyte transformation test was positive to ceftriaxone and negative to meropenem.Non-immediate T cell mechanism seems to be involved. Diagnosis work-up couldn't exclude cross-reactivity between ceftriaxone and meropenem.

Placental restriction of fetal growth reduces cutaneous responses to antigen after sensitization in sheep.

Prenatal and early childhood exposures are implicated as causes of allergy, but the effects of intrauterine growth restriction on immune function and allergy are poorly defined. We therefore evaluated effects of experimental restriction of fetal growth on immune function and allergic sensitization in adolescent sheep. Immune function (circulating total red and white blood cells, neutrophils, lymphocytes, monocytes, eosinophils, and basophils, and the antibody response to Clostridial vaccination) and responses to house dust mite (HDM) allergen and ovalbumin (OVA) antigen sensitization (specific total Ig, IgG1, and IgE antibodies, and cutaneous hypersensitivity) were investigated in adolescent sheep from placentally restricted (PR, n = 23) and control (n = 40) pregnancies. Increases in circulating HDM-specific IgE (P = 0.007) and OVA-specific IgE (P = 0.038) were greater in PR than control progeny. PR did not alter total Ig, IgG1, or IgM responses to either antigen. PR increased OVA-specific but not HDM-specific IgA responses in females only (P = 0.023). Multiple birth increased Ig responses to OVA in a sex-specific manner. PR decreased the proportion of positive cutaneous hypersensitivity responders to OVA at 24 h (P = 0.030) but had no effect on cutaneous responses to HDM. Acute wheal responses to intradermal histamine correlated positively with birth weight in singletons (P = 0.023). Intrauterine growth restriction may suppress inflammatory responses in skin downstream of IgE induction, without impairment in antibody responses to a nonpolysaccharide vaccine. Discord between cutaneous and IgE responses following sensitization suggests new mechanisms for prenatal allergy programming.

Predictors of delayed-type hypersensitivity to Candida albicans and anti-Epstein-Barr virus antibody among children in Kilimanjaro, Tanzania.

We evaluated sex, age, nutritional status, and infectious disease (ID) as predictors of two biomarkers of cell-mediated immunity (CMI), delayed-type hypersensitivity to Candida albicans (DTH-Candida), and anti-Epstein-Barr virus antibody (EBV Ab), among 200 children in Kilimanjaro, Tanzania. DTH-Candida, which decreases with compromised CMI, was positively associated with age (OR: 1.27; 95% CI: 1.02, 1.57) and triceps skinfold (TSF; OR: 1.16; 95% CI: 1.02, 1.26), and inversely associated with height-for-age Z score (HAZ; OR: 0.86; 95% CI: 0.68, 1.08) and diagnosed ID (OR: 0.48; 95% CI: 0.22, 1.08). There was significant interaction between TSF and ID: DTH-Candida exhibited a strong inverse association with ID among children with low TSF (OR: 0.16; 95% CI: 0.05, 0.50) and a strong positive association with TSF among children with ID (OR: 2.64; 95% CI: 1.29, 5.42). EBV Ab, which increases with compromised CMI, was inversely associated with male sex (ß: -0.47; 95% CI: -0.70, -0.24) and TSF (ß: -0.04; 95% CI: -0.08, 0.00), and positively associated with HAZ (ß: 0.06; 95% CI: -0.03, 0.15). Among males, EBV Ab was positively associated with anemia. Among normal HAZ children, EBV Ab was inversely associated with TSF. There was no association between DTH-Candida and EBV Ab. While DTH-Candida provides a direct measure of CMI, our results suggest that interpretation of EBV-Ab among Kilimanjaro children was complicated by its indirect relationship with CMI. Among our sample, CMI increased with age and adequate nutrition and was compromised during acute ID. The suggestive CMI-compromising effect of increasing height-for-age may bear further exploration.

Immunomodulatory and antioxidant effect of Leptadenia reticulata leaf extract in rodents: possible modulation of cell and humoral immune response.

CONTEXT: Leptadenia reticulata Linn. (Asclpiadaceae) commonly known as "dodi," is an Indian medicinal plant which is known to have ethno-medical uses such as stimulant, tonic, immunostimulant and is one of the ingredient in ayurvedic formulation called as "Chawanprash," which is widely used in India to increase the strength of immune system. OBJECTIVE: The aim of present study is to evaluate immunomodulatory and antioxidant activity of ethanolic extract of L. reticulata L. leaves in rodents. METHODS: Haemagglutinating antibody (HA) titre, haematological profile (Hb, WBC, RBC), lipid peroxidation (LPO), reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), delayed type of hypersensitivity (DTH) response, neutrophil adhesion test and carbon clearance assay were determined by in vivo experiments. RESULTS: The evaluation of immunomodulatory potential of L. reticulata (100, 200 mg/kg, p.o.) evoked a significant dose-dependent increase in antibody titre values; DTH reaction induced by SRBC and potentiated percentage neutrophil adhesion to nylon fibers as well as phagocytosis in carbon clearance assay. Also it caused significant increase in haematological profile, GSH, SOD, CAT activity and significantly decreased LPO levels in cyclophosphamide-induced immunosuppressed rats. CONCLUSION: The results obtained in this study indicate that L. reticulata possesses potential immunomodulatory and antioxidant activity and can play a major role in reducing the risk to develop immunodeficiency disorders.

[Three cases with high TARC levels of gastrointestinal food allergies in neonates and infants].

We measured serum TARC (Thymus and activation-regulated chemokine, CCL-17) levels in three patients of gastrointestinal food allergies in neonates and infants. Patient 1: 14-day-old girl. The chief complaints were poor feeding and weight loss. She tested peripheral eosinophilia (5820 /µL), high serum TARC levels (4730 pg/mL) and positive milk-specific IgE (1.53 UA/mL) at the time of onset. After change from cow' milk formula to hydrolyzed infant formulas and breast milk ahead of dairy products intake, the symptoms resolved. One month and a half later, she re-tested negative milk-specific IgE and normal serum TARC levels (198 pg/mL). Patient 2: 3-month-old girl. The chief complaint was vomiting after intake of cow' milk formula. She tested negative milk-specific IgE and very high serum TARC levels (25200 pg/mL) at the time of onset. After changing to hydrolyzed infant formulas and breast milk ahead of dairy products intake, the symptom resolved. Three months later, she re-tested positive milk-specific IgE (0.42 UA/mL) and normal serum TARC levels (1250 pg/mL). Patient 3: 21-day-old boy. The chief complaint was vomiting after intake of cow' milk formula. He tested peripheral eosinophilia (2923 /µL), very high serum TARC levels (49100 pg/mL) and positive milk-specific IgE (0.47 UA/mL) at the time of onset. After changing to hydrolyzed infant formulas and breast milk ahead of dairy products intake, the symptom resolved. Two weeks later, he re-tested negative milk-specific IgE and serum TARC levels (2210 pg/mL). Serum TARC may be related to the part of gastrointestinal food allergies in neonates and infants.

Cellular and humoral immune responses after short-term oral hormone therapy in postmenopausal women.

OBJECTIVE: To evaluate the cellular and humoral immune responses after oral hormone therapy in postmenopausal women. Study design This was a prospective cohort study, with intervention. The main outcome measures were delayed-type IV cell-mediated hypersensitivity, leukocytes, immunoglobulins, interleukin-6 (IL-6) and interleukin-10 (IL-10). METHODS: The delayed-type cell-mediated hypersensitivity was measured by using five common allergens before and after 3 months of hormone therapy. Each type of leukocyte cell was counted before and after hormone therapy. Different subtypes of lymphocytes were determined by flow cytometry. Immunoglobulins G, A and M were measured by nephelometry; immunoglobulin E was measured by electrochemiluminescence. IL-6 and IL-10 concentrations were determined by chemiluminescence. RESULTS: Hormone therapy increased the response to tuberculin antigen without changing the total number of leukocytes, eosinophils, neutrophils, lymphocytes, and CD4 +, CD8 + B cells. Both monocyte number and CD4 + /CD8 + ratio suffered a slight modification (p = 0.057). Immunoglobulins A, M and E remained unchanged and immunoglobulin G decreased (p = 0.029). IL-6 levels remained stable but IL-10 concentrations increased significantly after hormone therapy. CONCLUSION: Short-term oral hormone treatment has no impact on the cellular immune response but, concerning the humoral immune response, immunoglobulin G decreased and the levels of IL-10 were significantly higher.

The role of chemical mediators in the inflammatory response induced by foreign bodies: comparison with the schistosome egg granuloma.

Both divinyl benzene copolymer (plastic) beads and schistosome eggs produce inflammatory reactions after intravenous deposition into the lung of a mouse. As reported previously, the schistosome egg granuloma is an immunologic reaction of the delayed hypersensitivity type; this inflammatory process is prevented by immunosuppressive measures, and characteristically demonstrates an anamnestic response. In contradistinction, the plastic bead granuloma appears to be characteristic of a foreign body reaction; it is unaffected by immunosuppressive measures and does not demonstrate an anamnestic response with repeated exposure. The data in this report suggest that the granuloma formation around plastic beads is a nonimmunologic reaction induced by chemical mediators of inflammation. This proposal is supported by the following findings: the plastic beads activate Hageman factor in normal human and mouse plasma; the plastic beads induce vascular permeability-enhancing activity as measured in guinea pig skin and kinin-like activity in normal human and mouse plasma that is dependent on Hageman factor; ellagic acid, an agent that activates Hageman factor in vivo and is reported to diminish kininogen by consumptive depletion, markedly depresses the plastic bead granuloma. These data are consistent with the idea that the plastic bead granuloma and perhaps other foreign body inflammatory reactions are in major part dependent on kinin formation. Ellagic acid also suppressed the schistosome egg granuloma, but not to the same degree as the plastic bead granuloma. The implications of this observation are discussed in the text. Silicosis and "blue velvet disease", pathologic processes associated with the deposition of silica and magnesium trisilicate, respectively, in the lung, and the induction of a foreign body reaction may also be dependent on the activation of chemical mediators of inflammation by the silica and magnesium trisilicate particles with immunologic mechanisms participating in only a minor way, if at all. The marked suppression of experimental silicosis and blue velvet disease in mice by ellagic acid supports this idea.

On the number and nature of antigen-sensitive lymphocytes in the blood of delayed-hypersensitive human donors.

The virus plaque assay has been successfully employed to enumerate antigen-sensitive cells in the peripheral blood lymphocyte populations of tuberculin-hypersensitive human donors. The method is based on the finding that, while resting lymphocytes are unable to produce a variety of viruses upon infection, lymphocytes activated by specific antigens become capable of virus replication. The average number of antigen-sensitive cells detected in cell populations from donors reacting to first test strength or intermediate test strength tuberculin was approximately 3.6/1000 lymphocytes, and the averages for both groups were similar. Studies on the kinetics of appearance of these virus plaque-forming cells and on the effects of the mitotic inhibitor, vinblastine, indicate that the activation of these antigen-sensitive cells is a linear process and that the cells must be nondividing cells during this process. These qualities contrast markedly with those described for the mitogenic response and the antibody-producing cells which require cell division and increase exponentially. On the basis of these experiments it is suggested that the antigen-sensitive cell measured in the virus plaque assay is the effector cell in delayed-type hypersensitivity reactions and, in addition, may be one of the cells critically involved in antibody formation.

Plasma testosterone levels decrease after activation of skin immune system in a free-ranging mammal.

The immunocompetence handicap hypothesis (ICHH) postulates a trade-off between the display of androgen-related, sexually selected traits and investment in immune functions, often summarized as immunosuppression by testosterone (TE). We investigated the relationship between delayed type hypersensitivity (DTH) skin responses and the endocrine system in a free-ranging mammal and asked: (i) are high plasma TE levels related to a weak DTH response or (ii) does an activation of the cellular immune system cause a decrease in plasma TE secretion? and (iii) does baseline cortisol (CORT) and the capacity to release CORT in response to stress influence the DTH response? We studied these questions in the bat Carollia perspicillata and conducted an immune challenge (IC), a DTH skin test with the antigen 1,4-dinitrofluorobenzene (DNFB), as a measure for antigen-specific cell-mediated immunity. We found a high individual variance in DTH response irrespective of sex. In addition, pre-IC plasma TE did not affect the extent of DTH responses, but instead the IC lowered post-IC TE titres in both sexes. Also, pre-IC baseline CORT titres did not influence the DTH responses significantly, but the extent of an induced CORT response was negatively related to the DTH reaction. Our study does not support the presumption of an immunosuppressive effect of TE, but suggests that an activation of the immune system reduces plasma TE. This is still in line with the ICHH as originally formulated, because only immunocompetent animals are able to cope with pathogens effectively and maintain high TE levels at the same time.

In vivo immunomodulatory activities of the aqueous extract of bonduc nut Caesalpinia bonducella seeds.

This study evaluated the in vivo immunomodulatory activities of the aqueous extract of Caesalpinia bonducella Fleming (Caesalpiniaceae) seeds. C. bonducella is a plant widely used in the traditional medicinal systems of India. In the present investigation, the aqueous extract of C. bonducella seeds was tested for its effect on cell mediated and humoral components of the immune system in rats. Administration of C. bonducella seed extract produced an increase of 93.03 +/- 4 mean hemagglutinating antibody (HA) titer and a change of 0.56 +/- 0.058 mm in delayed type hypersensitivity (DTH) as compared to control at a dose of 400 mg/kg body weight. Thus, the results of this study indicate that C. bonducella extract could be a promising immunostimulatory agent.

Regulatory T Cells Developing Peri-Weaning Are Continually Required to Restrain Th2 Systemic Responses Later in Life.

Atopic disorders including allergic rhinitis, asthma, food allergy, and dermatitis, are increasingly prevalent in Western societies. These disorders are largely characterized by T helper type 2 (Th2) immune responses to environmental triggers, particularly inhaled and dietary allergens. Exposure to such stimuli during early childhood reduces the frequency of allergies in at-risk children. These allergic responses can be restrained by regulatory T cells (Tregs), particularly Tregs arising in the gut. The unique attributes of how early life exposure to diet and microbes shape the intestinal Treg population is a topic of significant interest. While imprinting during early life promotes the development of a balanced immune system and protects against immunopathology, it remains unclear if Tregs that develop in early life continue to restrain systemic inflammatory responses throughout adulthood. Here, an inducible deletion strategy was used to label Tregs at specified time points with a targeted mechanism to be deleted later. Deletion of the Tregs labeled peri-weaning at day of life 24, but not before weaning at day of life 14, resulted in increased circulating IgE and IL-13, and abrogated induction of tolerance towards new antigens. Thus, Tregs developing peri-weaning, but not before day of life 14 are continually required to restrain allergic responses into adulthood.

Enhanced contact hypersensitivity by delayed T-helper 2 response in BALB/c mice.

T-helper (Th) 1/Th2 balance determines the direction of contact hypersensitivity (CHS). To clarify the immunopathogenesis of contact dermatitis, 2,4-dinitrofluorobenzene (DNFB)-induced CHS reaction was compared between the BALB/c and C57BL/6 mice. The two strains were sensitized with DNFB systemically and challenged with DNFB locally. The CHS reaction in BALB/c mice was intense compared with that in C57BL/6 mice at 24 and 48 hours post-DNFB challenge. The dermal lesions were characterized by infiltration of lymphocytes, eosinophils, neutrophils, and macrophages including CD4+ and CD8+ T cells, and interleukin (IL)-4-producing(+) and interferon (IFN)-gamma+ cells in BALB/c mice. In C57BL/6 mice, the composition of inflammatory cells was same as those in BALB/c mice except for eosinophils, CD4+ T cells, and IL-4+ cells. There was no increase in the number of mast cells in the two strains. Local and systemic productions of IL-4 and IFN-gamma in BALB/c mice were higher than those in C57BL/6 mice. Although blood IgE values increased in BALB/c mice, but not in C57BL/6 mice, at 48 hours postchallenge, its value was low. The delayed Th2-like response together with Th1-like response in BALB/c mice may induce strong CHS reaction compared with C57BL/6 mice, which may dominantly develop Th1-like reaction. Moreover, mast cell and IgE do not appear to be involved in delayed CHS.

[Activation processes in the lymphocytes of patients with latent sensitization].

Latent sensitization is a risk factor of a clinically manifest atopic reaction. Investigation of a phenotypic composition of lymphocytes reveals function of the immune system in this condition. Indirect fluorescence assessed differential and activation lymphocyte antigens (CD4, CD3, CD8, CD16, CD20 and CD25, CD71, HLA-DR, CD95, CD23, CD54, respectively) in 15 patients with latent sensitization, 32 patients with atopic bronchial asthma and 22 healthy donors. The immune system demonstrated definite activation with involvement ofT- and B-links of the immune system. Lymphocyte activation in latent sensitization and bronchial asthma differs by high expression of CD95 apoptosis trigger receptor. Enhancement of Fas-mediated lymphocyte apoptosis may inhibit IgE synthesis and atopic pathology manifestation.

Evaluation of immunomodulatory activity of methanolic extract of Piper betel.

Many of the disorders today are based on the imbalances of immunological processes. This necessitates the search for newer and safer immunomodulators. Thus, the objective of the present study was to explore the immunomodulatory activity of the methanolic extract of Piper betel L. (MPb) (Family: Piperaceae). The MPb consists of mixture of phenols, flavonoids, tannins and polysaccharides. Both in vitro as well as in vivo evaluation was carried out. The effects of MPb on lymphocyte proliferation, interferon-gamma receptors and the production of nitric oxide were measured in vitro. Further, the extract at different dose levels was studied in vivo for the humoral and cellular immune responses on mice immunized with sheep red blood cells. P. betel significantly suppressed phytohaemagglutinin stimulated peripheral blood lymphocyte proliferation in a dose-dependent manner. The decrease in antibody titre and increased suppression of inflammation suggests possible immunosuppressive effect of extract on cellular and humoral response in mice. Thus, the MPb could be explored extensively as a therapeutic agent to treat various immune disorders including autoimmune disorders.

Control of delayed-type hypersensitivity by ocular- induced CD8+ regulatory t cells.

The immunoregulatory pathway from the eye to the peri - pheral immune system is comprised of the iris, ciliary body, circulation, thymus and spleen, and is influenced by the sympathetic nervous system. At the splenic end of this pathway are antigen-specific CD8+ regulatory T cells (Tregs) that mediate directly the suppression of T cells that effect delayedtype hypersensitivity (DTH). Here we review investigations that demonstrate: (i) the injection of antigen into the anterior chamber (AC) attracts circulating monocytic cells to the iris/ciliary body that recirculate to the thymus and spleen. In the thymus, ocular-influenced monocytic cells activate natural killer T (NKT) cells that migrate to the spleen where, in concert with the ocular-influenced monocytic emigrants, they (ii) activate CD4+ and CD8+ immunoregulatory T cells. (iii) The generation of the CD8+ Tregs is dependent on NKT cells in the thymus and the periphery that are influenced by the sympathetic nervous system. (iv) The suppression of DTH by the AC-induced CD8+ Tregs is dependent on the cytokines transforming growth factor-Beta and interferon-gamma and is restricted by the expression of major histocompatibility complex-associated Qa-1b antigens. In aggregate, this oculothymic- splenic pathway is a well-controlled response to ocular injury that utilizes a systemic response to antigen that may protect ocular tissue and systemic tissue.

Suppression of T lymphocyte activation by 3-chloro-1,2-propanediol mono- and di-palmitate esters in vitro.

This study investigated whether and how 3-chloro-1,2-propanediol (3-MCPD) fatty acid esters, a group of food contaminants formed during processing, might inhibit the immune system through suppressing T lymphocyte activation for the first time. Three 3-MCPD esters including 1-palmitoyl-3-chloropropanediol (1-pal), 2-palmitoyl-3-chloropropanediol (2-pal), and1,2-dipalmitoyl-3-chloropropanediol (dipal) were selected as the probe compounds to test the possible effects of fatty acid structure on their potential immune inhibitory effect. The results showed that 1-pal and 2-pal, but not dipal, significantly suppressed ConA-induced T lymphocyte proliferation, cell cycle activity, Th1 and Th2 cytokine secretion, CD4+ T cell populations, and the ratio of CD4+/CD8+ T cells under the experimental conditions. Moreover, Western blotting and immunofluorescence analyses revealed that 1-pal and 2-pal could inhibit the activation of ConA-stimulated mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) signaling pathways. In addition, 1-pal significantly suppressed DNFB-induced delayed-type hyper sensitivity (DTH) reaction characterized by the increased ear thickness and IFN-γ production in mice. These observations indicated that 3-MCPD esters exerted a negative effect on T lymphocyte-mediated immunity, and the immunosuppressive activities of 3-MCPD monopalmitates were stronger than 3-MCPD dipalmitate.