Delayed-type Hypersensitivity Response Research Articles

Investigation of immunomodulatory activity of hericium erinaceus on cyclophosphamide-induced immunosuppression in mice

The study was conducted to assess the immunostimulatory effect of Hericium Erinaceus on cyclophosphamide-induced immunodeficient mice. Animals were administered Hericium Erinaceus orally at 0.72 g/kg b.w and 1.44 g/kg b.w for seven consecutive days. On the 4th day, CP (200 mg/kg) was intraperitoneally injected into mice. The results illustrated that Hericium Erinaceus at 0.72 g/kg b.w only posed an immunostimulating potency in the cyclophosphamide-induced immunosuppression model. Besides, Hericium Erinaceus at 1.44 g/kg b.w ameliorated the effects of CP on delayed-type hypersensitivity (DTH) response, relative spleen weight, serum IL-2, TNF-α concentration, and micro-histological images of spleen and thymus substantially. This suggested the potential of Hericium Erinaceus to treat immunosuppression diseases in clinical practice.

The role of intralesional immunotherapy in Condyloma Acuminata

Intralesional immunotherapy is one of the immunotherapy modalities that can be given to patients with condyloma acuminata (CA) with a high success rate both in inhibiting progression and preventing recurrence of genital warts. Intralesional immunotherapy regimens that are currently being studied are the use of vaccines and cytokines. Some of the antigens studied for use as therapy in genital warts include Candida albicans, measles, mumps and rubella (MMR), and Tuberculin/Purified Protein Derivate (PPD), Mycobacterium w, and Bacille Calmette-Guerin (BCG). Vaccines and cytokines work by inducing a delayed-type hypersensitivity response to warts tissue, both through cellular and humoral immune responses, mediated by CD8+ T lymphocytes, CD4+ T lymphocytes, B lymphocytes and regulatory T cells so that this can eliminate HPV virus infection in CA. This literature review aims to provide an understanding of the use of intralesional immunotherapy as an effective alternative therapy in CA.

IMMUNOSTIMULANT ACTIVITY OF HANTAP (STERCULIA COCCINEA JACK) LEAVES EXTRACT ON NON-SPECIFIC AND SPESIFIC IMMUNE RESPONSES

Objective: This study aims to determine the immunostimulant effect and the effective dose of hantap leaf ethanolic extract against non-specific and specific immune responses.
 Methods: The immunostimulant activity of the extract was tested by the carbon clearance method (non-specific response). The effect of the extract on delay-type hypersensitivity/DTH (cellular-specific response) was determined by the paw edema method. The number of leukocyte cells and the percentage of leukocyte cell types were also calculated. The antibody titer (humoral-specific response) test was carried out by the hemagglutination method.
 Results: The results of the non-specific immune response demonstrated that three doses of hantap leaf extract, when compared to the negative control, could accelerate the rate of carbon elimination and increase the phagocytosis index. Hantap leaf extract can provide an immunomodulatory effect by increasing the delayed-type hypersensitivity response by showing a greater volume of leg swelling than the negative control received CMC Na 0.5%, which was significantly different (p<0.05), increasing leukocyte count and leukocyte differential and increasing primary and secondary antibody titers. The effective dose of hantap leaves extract was 200 mg/kg body weight.
 Conclusion: This study proves that hantap leaf extract has an immunomodulatory effect that increases the immune system (immunostimulant)

A Comparative Study on the Mechanism of Delayed-Type Hypersensitivity Mediated by the Recombinant Mycobacterium tuberculosis Fusion Protein ESAT6-CFP10 and Purified Protein Derivative

While purified protein derivative (PPD) is commonly used as skin diagnostic reagent for tuberculosis (TB) infection, it cannot distinguish effectively Bacillus Calmette–Guérin (BCG) vaccination from Mycobacterium tuberculosis (MTB) complex and nontuberculous mycobacteria infection. The new skin reagent ESAT6-CFP10 (EC) has favorable sensitivity and specificity, which can overcome limitations associated with PPD. At present, EC skin test reactions are mainly characterized by erythema, while PPD mainly causes induration. We conducted a comparative study on the potential differences between EC-induced erythema and PPD-induced induration using a guinea pig model. The size of EC-dependent erythema was similar to that of PPD-induced induration, and an inflammatory response characterized by the infiltration of monocytes, macrophages and lymphocytes, as well as tissue damage, appeared at the injection site. The lymphocytes included CD4+ T and CD8+ T cells, which released IFN-γ as the main cytokine. Both EC erythema and PPD induration could lead to increased levels of acute-phase proteins, and the differential pathways were similar, thus indicating that the main induced immune pathways were similar. The above results indicated that erythema produced by EC could generate the main delayed-type hypersensitivity (DTH) response characteristic of PPD induration, thereby suggesting that erythema might also have a certain diagnostic significance and provide a possible theoretical basis for its use as a diagnostic indicator for detecting MTB infection.

Headache as initial presentation of human chronic necrotizing granulomatous meningoencephalitis: A rare case report

Chronic necrotizing granulomatous meningoencephalitis is an idiopathic inflammatory disease with possible autoimmune mediated delayed type hypersensitivity response. It commonly affects the central nervous system of dogs, and on rare occasions cats. However, this inflammatory disease has rarely been reported in humans. A 69-year-old woman presented with subacute intermittent sharp headaches. Brain MRI revealed multifocal enhancing lesions and edema as well as multifocal signal abnormality throughout the supratentorial and infratentorial parenchyma. Cerebrospinal fluid showed elevated opening pressure, pleocytosis, and elevated protein. MRA head, MRV head, cerebral angiogram, extensive serum and CSF work up for infectious and autoimmune etiologies were also unremarkable. Brain biopsy revealed necrotizing granulomatous inflammation with dystrophic calcification. High dose of methylprednisolone followed by a 6-week prednisone taper resolved her headache and the brain MRI abnormalities. This case demonstrates the response of necrotizing granulomatous meningoencephalitis in humans to steroids.

Isolation of a novel pentasaccharide Ebaliose from immunostimulant fraction of buffalo milk oligosaccharide

Buffalo milk processed by method of Kobata and Ginsburg for isolation of its oligosaccharide contents showed significant stimulation of anti-body, delayed type hypersensitivity response to sheep red blood cells in BALB/c mice. This oligosaccharide mixture also stimulated non-specific immune response in terms of MMI. In continuation to our previous studies of oligosaccharide contents of buffalo milk another novel pentasaccharide Ebaliose was isolated from immunostimulant oligosaccharide fraction of buffalo milk. Ebaliose was procured in its purest form, by combining the different chromatographic techniques like Gel filtration, Silica Gel column chromatography, and HPLC. The structure of novel oligosaccharide was determined by 1H,13C, HSQC, TOCSY, COSY, HMBC, ESI-MS, chemical transformation, and chemical degradation. The stereoscopic structure of this novel pentasaccharide was established as under.

FORMULATION AND EVALUATION OF HERBAL CAPSULE CONTAINING CURCUMA MANGGA VALETON and ZIJP. EXTRACT AND ITS IMMUNOSTIMULATORY EFFECTS

Objective: The present study was carried out to formulate and evaluate C. mangga extract as granule mass in a capsule dosage form as well as investigate its immunostimulatory effects. Methods: The granule mass was evaluated for its bulk density, tapped density, Carr’s index, Hausner ratio, angle of repose, and flow ability. Meanwhile, capsule weight and disintegration time were determined to evaluate the C. mangga capsule. The immunostimulatory effects of extract in capsule dosage form were investigated by measuring delayed-type hypersensitivity (DTH) response and IgG production. There were six formula prepared (F1-F6). Formula F1-F6 were vary according to the component of adsorbent (Corn starch/polyvinyl pyrrolidone) and filler (maltodextrin/Avicel/lactose) to obtain the optimum formula. Results: The granule mass of all formula had a good flow ability and free-flowing properties according to the Carr’s index (10.26±3.38 to 17.54±1.60) and flowing time (1.05±0.05 to 1.60±0.08 seconds). Of all the capsule formula, F2 capsule containing dry extract of C. mangga with Avicel as the filler met the standard requirement in terms of disintegration time (2.15±0.76 min) and weight uniformity (the deviation was below than 7.5%). The capsule of C. mangga extract enhanced the paw thickness as compared to those of the negative control (P<0.05). The level of Immunoglobulin G (IgG) was also increased after treatment with the capsule of C. mangga extract. Conclusion: The results suggest that the capsule of C. mangga extract has immunostimulatory effects, emphasizing its potential to be used for the treatment of infectious and immunodeficiency diseases.

Melittin as a safe compound to BALB/c mice immune system; a tiered approach immunotoxicity screening

BackgroundMaintenance of immune system integrity is a vital requirement to protect human body against pathogens/cancers. Natural compounds have long been used due to their benefits for the immune system. One of which is bee venom that contains a peptide called melittin having antimicrobial and anticancer effects. Since a limited number of studies regarding the effects of melittin on the immune system have been carried out, we aimed to evaluate the effects of melittin on BALB/c mice immune system parameters.MethodsFemale BALB /c mice were treated intraperitoneally (i.p) with 0.75 and 1.5 mg/kg doses of melittin for 14 days (5 doses per week). The negative control group received i.p normal saline whereas the positive controls received i.p 20 mg/kg cyclophosphamide (CYP). Immunological parameters such as hematological parameters, delayed-type hypersensitivity (DTH), hemagglutination titer (HA), spleen cellularity, splenocytes proliferation, as well as spleen and bone marrow histopathological assessment were evaluated.ResultsOur findings showed that melittin has no gross pathological effect on the spleen and bone marrow. It was also demonstrated that melittin has no any significant effect on hematological parameters. Melittin did not cause any significant changes to proliferation response of splenocytes to PHA and LPS, spleen cellularity, DTH response, as well as the production of anti-SRBC antibodies. According to our results, melittin at 0.75 and 1.5 mg/kg doses could not induce significant changes on immune parameters and as a result, melittin was found to be safe for the mice immune system.

Comparison of the effects of probiotic strains (Lactobacillus gasseri, Lactiplantibacillus plantarum, Lactobacillus acidophilus, and Limosilactobacillus fermentum) isolated from human and food products on the immune response of CT26 tumor-bearing mice.

This study aimed to compare the effects of the probiotic bacteria, L. gasseri (52b), L. plantarum (M11), L. acidophilus (AC2), and L. fermentum (19SH), isolated from human source and traditional food products on the modulation of the immune system and inflammatory response on BALB/c mouse model bearing CT26 tumor. Five groups of female inbred BALB/c mice were orally administered with the probiotics and their mixes (MIX, at a 1:1 ratio) at varying dosages (1.5 × 108cfu/ml and 1.2 × 109cfu/ml) before and after the injection of a subcutaneous CT26 tumor over the course of 38days via gavage. Finally, their effects on the tumor apoptosis and the cytokine levels in spleen cell cultures were analyzed and compared. M11, MIX, and 52b groups had the greatest levels of interleukin-12 (IL-12) and interferon gamma (IFN-γ) production. The highest production level of granzyme B (GrB) was related to the MIX and 52b groups. Moreover, these groups showed the lowest production level of (IL-4) and transforming growth factor beta (TGF-β). Furthermore, the groups of MIX and 52b demonstrated the greatest amount of lymphocyte proliferation of spleen cells in response to the tumor antigen. The delayed-type hypersensitivity (DTH) response significantly increased in the groups of MIX and 52b compared with the control (p < 0.05). The findings demonstrated that the oral treatment of the human strain (52b) and the combination of these bacteria generated strong T helper type 1 (Th1) immune responses in the tumor tissue of the tumor-bearing mice, which led to the suppression of the tumor development.

Individual and sociodemographic factors associated with polysensitization at a New York City hospital

Allergic contact dermatitis (ACD) is a cutaneous delayed-type hypersensitivity response with a global prevalence estimated at over 20%.1 The gold standard for diagnosis is patch testing, in which allergens are applied to a patient's skin to elicit cutaneous responses in sensitized individuals. Many patients undergoing patch testing test positive for 3 or more unrelated allergens, termed polysensitization.2 A recent North American Contact Dermatitis Group study found that 32.1% of patients tested were positive to at least three allergens, but reported rates vary.3

Fundamental Characterization of Antibody Fusion-Single-Chain TNF Recombinant Proteins Directed against Costimulatory TNF Receptors Expressed by T-Lymphocytes.

The costimulatory signal regulated by the members of the tumor necrosis factor receptor (TNFR) superfamily expressed by T cells plays essential roles for T cell responses and has emerged as a promising target for cancer immunotherapy. However, it is unclear how the difference in TNFR costimulation contributes to T cell responses. In this study, to clarify the functional significance of four different TNFRs, OX40, 4-1BB, CD27 and GITR, we prepared corresponding single-chain TNF ligand proteins (scTNFLs) connected to IgG Fc domain with beneficial characteristics, i.e., Fc-scOX40L, Fc-sc4-1BBL, Fc-scCD27L (CD70) and Fc-scGITRL. Without intentional cross-linking, these soluble Fc-scTNFL proteins bound to corresponding TNFRs induced NF-kB signaling and promoted proliferative and cytokine responses in CD4+ and CD8+ T cells with different dose-dependencies in vitro. Mice injected with one of the Fc-scTNFL proteins displayed significantly augmented delayed-type hypersensitivity responses, showing in vivo activity. The results demonstrate that each individual Fc-scTNFL protein provides a critical costimulatory signal and exhibits quantitatively distinct activity toward T cells. Our findings provide important insights into the TNFR costimulation that would be valuable for investigators conducting basic research in cancer immunology and also have implications for T cell-mediated immune regulation by designer TNFL proteins.

Nasal immunization with H7 flagellin protects mice against hemolytic uremic syndrome secondary to Escherichia coli O157:H7 gastrointestinal infection.

Shiga-toxin (Stx) producing Escherichia coli (STEC) O157:H7 is the most frequent serotype associated with hemolytic uremic syndrome (HUS) after gastrointestinal infections. Protection against HUS secondary to STEC infections has been experimentally assayed through the generation of different vaccine formulations. With focus on patients, the strategies have been mainly oriented to inhibit production of Stx or its neutralization. However, few approaches have been intended to block gastrointestinal phase of this disease, which is considered the first step in the pathogenic cascade of HUS. The aim of this work was to assay H7 flagellin as a mucosal vaccine candidate to prevent the systemic complications secondary to E. coli O157:H7 infections. The cellular and humoral immune response after H7 nasal immunization in mice were studied by the analysis of systemic and intestinal specific antibody production, as well as cytokine production and lymphocyte proliferation against H7 flagellin ex vivo. Immunized mice developed a strong and specific anti-H7 IgG and IgA response, at systemic and mucosal level, as well as a cellular Th1/Th2/Th17 response. H7 induced activation of bone marrow derived dendritic cells in vitro and a significant delayed-type hypersensitivity (DTH) response in immunized mice. Most relevant, immunized mice were completely protected against the challenge with an E. coli O157:H7 virulent strain in vivo, and surviving mice presented high titres of anti-H7 and Stx antibodies. These results suggest that immunization avoids HUS outcome and allows to elicit a specific immune response against other virulence factors.

Quillaja brasiliensis nanoparticle adjuvant formulation improves the efficacy of an inactivated trivalent influenza vaccine in mice.

The threat of viral influenza infections has sparked research efforts to develop vaccines that can induce broadly protective immunity with safe adjuvants that trigger robust immune responses. Here, we demonstrate that subcutaneous or intranasal delivery of a seasonal trivalent influenza vaccine (TIV) adjuvanted with the Quillaja brasiliensis saponin-based nanoparticle (IMXQB) increases the potency of TIV. The adjuvanted vaccine (TIV-IMXQB) elicited high levels of IgG2a and IgG1 antibodies with virus-neutralizing capacity and improved serum hemagglutination inhibition titers. The cellular immune response induced by TIV-IMXQB suggests the presence of a mixed Th1/Th2 cytokine profile, antibody-secreting cells (ASCs) skewed toward an IgG2a phenotype, a positive delayed-type hypersensitivity (DTH) response, and effector CD4+ and CD8+ T cells. After challenge, viral titers in the lungs were significantly lower in animals receiving TIV-IMXQB than in those inoculated with TIV alone. Most notably, mice vaccinated intranasally with TIV-IMXQB and challenged with a lethal dose of influenza virus were fully protected against weight loss and lung virus replication, with no mortality, whereas, among animals vaccinated with TIV alone, the mortality rate was 75%. These findings demonstrate that TIV-IMXQB improved the immune responses to TIV, and, unlike the commercial vaccine, conferred full protection against influenza challenge.

Mesenchymal Stromal Cells Suppress T-Cell-Mediated Delayed-Type Hypersensitivity via ALCAM-CD6 Interaction.

Mounting evidence suggests mesenchymal stromal cells (MSCs) suppress CD4+ T-cell activation, but whether MSCs directly regulate activation and expansion of allogeneic T cells has not been fully deciphered. Here, we identified that both human and murine MSCs constitutively express ALCAM, a cognate ligand for CD6 receptors on T cells, and investigated its immunomodulatory function using in vivo and in vitro experiments. Our controlled coculture assays demonstrated that ALCAM-CD6 pathway is critical for MSCs to exert its suppressive function on early CD4+CD25- T-cell activation. Moreover, neutralizing ALCAM or CD6 results in the abrogation of MSC-mediated suppression of T-cell expansion. Using a murine model of delayed-type hypersensitivity response to alloantigen, we show that ALCAM-silenced MSCs lose the capacity to suppress the generation of alloreactive IFNγ-secreting T cells. Consequently, MSCs, following ALCAM knockdown, failed to prevent allosensitization and alloreactive T-cell-mediated tissue damage.

Unwinding the mechanism of macrophage repolarization potential of Oceanimonas sp. BPMS22-derived protein protease inhibitor through Toll-like receptor 4 against experimental visceral leishmaniasis.

The Oceanimonas sp. BPMS22-derived protein protease inhibitor (PPI) has been proven to shift macrophages towards an inflammatory state and reduce Leishmania donovani infection in vitro and in vivo. The current study explored and validated the mechanistic aspects of the PPI and Toll-like receptor (TLR) interaction. The PPI exhibited the upregulation of TLR2, TLR4, and TLR6 during treatment which was proven to orchestrate parasite clearance effectively. An in silico study confirmed the high interaction with TLR4 and PPI. Immune blotting confirmed the significant upregulation of TLR4 in macrophages irrespective of L. donovani infection. Pharmacological inhibition and immune blot study confirmed the involvement of the PPI in TLR4-mediated phosphorylation of p38 MAPK and dephosphorylation of ERK1/2, repolarizing to pro-inflammatory macrophage state against experimental visceral leishmaniasis. In addition, in TLR4 knockdown condition, PPI treatment failed to diminish M2 phenotypical markers (CD68, Fizz1, Ym1, CD206, and MSR-2) and anti-inflammatory cytokines (IL-4, IL-10, and TGF-β). Simultaneously, the PPI failed to upregulate the M1 phenotypical markers and pro-inflammatory cytokines (IL-1β, IL-6, IL-12, and IFN-γ) (p < 0.001) during the TLR4 knockdown condition. In the absence of TLR4, the PPI also failed to reduce the parasite load and T-cell proliferation and impaired the delayed-type hypersensitivity response. The absence of pro-inflammatory cytokines was observed during a co-culture study with PPI-treated macrophages (in the TLR4 knockdown condition) with day 10 T-cell obtained from L. donovani-infected mice. This study supports the immunotherapeutic potential of the PPI as it interacted with TLR4 and promoted macrophage repolarization (M2-M1) to restrict the L. donovani parasite burden and helps in the mounting immune response against experimental visceral leishmaniasis.

Evaluation of Immunomodulatory Effect of Aqueous Extract of Bauhinia variegata L. Leaves

Abstract: Natural products have the potential to modulate the immunity of human beings either by stimulating or depressing it and the approach was being used over time by medicinal practitioners to treat ailments. This present study was planned to ascertain the immunomodulating potential of one of the Indian traditional medicinal plants Bauhinia variegata L. The aqueous extract of powdered leaves of Bauhinia variegata L. was prepared by using the decoction method and the extract was then dried and made free from solvent. The extract of Bauhinia variegata L. (BVAE) was screened for immunomodulating activity by hemagglutination reaction for humoral and delayed-type hypersensitivity study for cellular immune responses. The sheep RBC (5X109 cells/ mL) was used as antigen and levamisole was used as the standard drug in both studies. The extract of plant material (BVAE) showed a dose-dependent response in these studies. BVAE at 400 mg/ kg dose among all the doses of plant material showed significantly (p<0.05) high antibody titer 7.13±0.17) in humoral immune response and potential delayed-type hypersensitivity response (0.96±0.06) in the cellular immune study. Whereas, the standard drug levamisole showed the most significant (p<0.01) higher antibody titer (7.87±0.19) and delayed-type hypersensitivity response (1.24±0.04). Though the standard drug showed a better response the plant material also showed the potential immunomodulatory effect in the present study. Hence, the findings of this study proposed the immunomodulatory effect of the aqueous extract of Bauhinia variegata L., and 400 mg/kg dose of the extract was found to be potent among other doses. Keywords: Bauhinia variegata, Cellular immune response, Haemagglutination, Humoral study, Immunomodulation.

Abstract P4-07-23: Results of a Phase 2 Trial of Combination Immunotherapy with Concurrent Nelipepimut-S + GM-CSF and Trastuzumab in High-risk HER2+ Breast Cancer Patients

Abstract INTRODUCTION: The HER2-targeted peptide vaccine nelipepimut-S + GM-CSF (NeuVax) has been shown to be safe, immunogenic, and potentially synergistic with trastuzumab. Here we present the results of a randomized phase 2 trial assessing the ability of nelipepimut-S/GM-CSF versus GM-CSF alone, added to the standard adjuvant Trastuzumab, to prevent recurrences in high-risk HER2-positive breast cancer patients. METHODS: The study was a multi-center, prospective, randomized, controlled, single-blinded, phase 2 trial. Enrolled patients had high risk HER2+ breast cancer defined by the presence of residual disease post neoadjuvant therapy or by the presence of positive lymph nodes after upfront surgery. Eligible patients had completed an approved trastuzumab-chemotherapy containing regimen and they were receiving adjuvant Trastuzumab monotherapy. Enrollment was limited to patients with HLA-A2, A3, A24, and/or A26 alleles. Patients received intradermal injections of nelipepimut-S + GM-CSF or placebo + GM-CSF every three weeks for six total vaccinations with concurrent, standard monotherapy with iv trastuzumab. After completion of the primary vaccine series, booster inoculations were administered every six months for four doses. The primary outcome measure was invasive disease-free survival (iDFS) at 36 months. Secondary outcome measures were distant recurrence-free survival (DRFS), toxicity assessment, and evaluation of immune response. RESULTS: 100 patients were enrolled and randomized 1:1 to nelipepimut-S/GM-CSF or GM-CSF alone. There were no significant clinicopathologic differences between the groups. There was no difference in related local (p=0.49) or systemic toxicities (p=0.41). Kaplan-Meier estimates of iDFS at 36 months were 79% in the nelipepimut-S arm and 92% in the placebo arm (log rank, p=0.11). DRFS at 36 months was estimated to be 90% in the nelipepimut-S arm and 95% in the placebo arm (log rank, p=0.40). Delayed type hypersensitivity (DTH) response to nelipepimut-S was measured and considered positive if there was more than 5 mm induration after 48 hours. DTH response converted from negative to positive in 11% of patients in the vaccine group versus 5% of patients in the placebo group (p=0.36). In both groups, iDFS at 36 months was 100% for those with a positive DTH response post-inoculation and 88% for those with a negative DTH response post-inoculation (log rank, p=0.29). CONCLUSION: Combination immunotherapy with concurrent nelipepimut-S + GM-CSF and trastuzumab is safe, however there was no difference in iDFS or DRFS among high-risk HER2+ breast cancer patients who received nelipepimut-S + GM-CSF compared to GM-CSF alone. We observed a trend towards improved iDFS in patients with a positive DTH response to nelipepimut-S, though it was not statistically significant. Citation Format: Ankur Tiwari, Guy Clifton, Carmen Calfa, Gheath Alatrash, Jarrod Holmes, Isabelle Bedrosian, George Peoples, Elizabeth A. Mittendorf. Results of a Phase 2 Trial of Combination Immunotherapy with Concurrent Nelipepimut-S + GM-CSF and Trastuzumab in High-risk HER2+ Breast Cancer Patients [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-07-23.

Immuno-modulatory Effects of Inactivated Dietzia Maris on the Selected Aspects of Cellular and Humoral Immune Responses in Mice.

The current study is an attempt to register the alterations in the immunological and histological parameters in mice arising from the administration of Dietza maris (D. maris) in order to confirm its protective properties. Mice underwent 7 days of treatment with three doses of D. maris. Then, animals were scrutinized in terms of body weight, relative weight of organs, delayed type of hypersensitivity (DTH) response, and hemagglutination titer (HT). The determination of villus height, villus width, crypt depth, villus/crypt ratio (V/C), Goblet cells, and intestinal epithelial lymphocyte (IEL) density in villi was carried out. A boosted DTH response was observed as a result of bacteria at medium dose. A variation was noted between the hemagglutinin titer of the control group and that of the high-dose group. Crypt depth, villus width, and villus height manifested alterations. High-dose-treated mice demonstrated proliferation of Goblet cells in the villi, whereas both in medium- and high-dose-treated mice, a distribution of IELs in the villus epithelium was noted. Overall, D. maris showed a stimulatory effect on immune functions in mice. Thus, thanks to improved cellular and humoral immunity and the increased quality of intestine function, we believe that D. maris promises novel therapeutic applications in the future. The attained findings lend credence to immuno-stimulatory effects arising from the capacity of D. maris to function as immunological adjuvants and to enhance humoral and cellular immunity as well as the intestinal structure and function.

A case of symmetrical drug-related intertriginous and flexural exanthema

Symmetrical drug-related intertriginous and flexural exanthema (also known as Baboon syndrome) is a skin eruption in the intertriginous areas. It is believed to be a delayed-type hypersensitivity response to the drug which occurs secondary to systemic absorption of agents after cutaneous sensitization. Our case provides high quality clinical images to aid in clinical diagnosis of this uncommon skin eruption.

Immunomodulatory Effects of Phaleria macrocarpa Leaf Extract in Normal And Cyclophosphamides Induced in Wistar Rats

Abstract. Cyclophosphamide is an antineoplastic drug belonging to the alkylating agents commonly used in treating cancer. However, the use of cyclophosphamide causes a decrease in the body's immune system by reducing lymphocyte proliferation. The curent study was conducted to evaluate the immunomodulatory effect of ethyl acetate extracts of the leaf of the P. macrocarpa (EEADMD) and the ethanol extracts of the leaf of the P. macrocarpa (EEDMD) in normal and cyclophosphamide induced rats. This study used rats classified into two major groups: normal rats and rats induced by cyclophosphamide which were then given P. macrocarpa leaf extract until day 14. On day 4, the test animals were infected with 1% Staphylococcus aureus suspension in. Induced with cyclophosphamide 70 mg/kg BW was carried out on the 8th and 13th days, and then the immunomodulatory activity was tested using total leukocyte analysis, leukocyte differential, and delayed type hypersensitivity response. The results showed that EEDMD 400 mg/kg BW in normal rats and EEDMD 100 mg/kg BW in cyclophosphamide induced rats could increase total leukocytes and leukocyte differential with a significant difference to the negative group (p &lt;0.05). The results of the delayed hypersensitivity response test of EEADMD and EEDMD at a dose of 100 mg/kg BW with cyclophosphamide induction and normal rats could give an increase in rat paw volume with a significant difference to the negative group (p &lt;0.05). This study shows that EEADMD and EEDMD have an immunomodulatory effect on increasing total and differential leukocytes and leukocyte differential and delayed type hypersensitivity response.