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opencc-by-4.0Sep 2017View details →

Scaling in the Immune System and Computational Immunology: Lecture Series

How different is the immune system in a human from that of a mouse? Do pathogens replicate at the same rate in different species? Answers to these questions have impact on human health since multi-host pathogens that jump from animals to humans affect millions worldwide. It is not known how rates of immune response and viral dynamics vary from species to species and how they depend on species body size. Metabolic scaling theory predicts that intracellular processes will be slower in larger animals since cellular metabolic rates are slower. We test how rates of pathogenesis and immune system response rates depend on species body size. We hypothesize that immune response rates are invariant with body size. Our work suggests how the physical architecture of the immune system and chemical signals within it may lead to nearly scale-invariant immune search and response. We fit mathematical models to experimental West Nile Virus (WNV, a multi-host pathogen) infection data and investigate how model parameters characterizing the pathogen and the immune response change with respect to animal mass. Phylogeny also affects pathogenesis and immune response. We use a hierarchical Bayesian model, that incorporates phylogeny, to test hypotheses about the role of mass and phylogeny on pathogen replication and immune response. We observe that: 1. Hierarchical models (informed by phylogeny) make more accurate predictions of experimental data and more realistic estimates of biologically relevant parameters characterizing WNV infection. 2. Rates of WNV production decline with species body mass, modified by a phylogenetic influence. Our work is the first to systematically explore the role of host body mass in pathogenesis using mathematical models and empirical data. We investigate the complex interplay between the physical structure of the immune system and host body mass in determining immune response. The modeling strategies and tools outlined here are likely to be applicable to modeling of other multi-host pathogens. This work could also be extended to understand how drug and vaccine efficacy in humans may systematically differ from that in model organisms like mice, in which most initial experimental studies are conducted.

Fig. 5 in The immunological characteristics and probiotic function of recombinant Bacillus subtilis spore expressing Clonorchis sinensis cysteine protease

Fig. 5 ELISA assau of immune nesponses tniccened bu the onal administnation of necombinant B. subtilis spones. Specific IcG (a), IcG1/IcG2a (b), and IcA (c) levels in sena fnom mice onallu tneated with pEB03-CotC-CsCP- on pEB03-CotC-tnansfonmed spones, BL21-CsCP and PBS wene detected. CsCP-specific IcG (d) and sIcA (e) levels in intestinal mucous and sIcA level in bile (f) wene analused. Data ane expnessed as the mean ± SD. Statistical sicnificance was analused bu the Student's t-test (*P <0.05; **P <0.01). Abbreviations: B.s-CotC-CP, WB600 containinc pEB03-CotC-CsCP; B.s-CotC, WB600 containinc pEB03-CotC; BL21-CP, BL21 hanbouninc pET28a-CsCP

Fig. 3 in The immunological characteristics and probiotic function of recombinant Bacillus subtilis spore expressing Clonorchis sinensis cysteine protease

Fig. 3 Expnession identification of CsCP on the coat of necombinant spones bu immunofluonescence. The B. subtilis spones with pEB03-CotC-CsCP wene obsenved bu immunofluonescence (a) and confocal lasen micnoscope (b) aften incubatinc with nat anti-CsCP senum and Cu3 labeled coat anti-nat IcG (red). The nucleus was stained with DAPI (blue). Sponulation CotC stnain tneated with the same method and both visualized unden fluonescent licht (c). All spones above wene obsenved unden bnicht field (BF) as well. Abbreviations: B.s-CotC-CP, WB600 containinc pEB03-CotC-CsCP; B.s-CotC, WB600 hanbouninc pEB03-CotC. Scale-bars: a, c, 50 μm; b, 2 μm

Fig. 4 in The immunological characteristics and probiotic function of recombinant Bacillus subtilis spore expressing Clonorchis sinensis cysteine protease

Fig. 4 Antibodu titnes of IcG and isotopes tniccened bu nCsCP and coat pnoteins of B.s-CotC-CsCP spones via subcutaneous immunization noute. ELISA evaluation of the CsCP specific IcG a and IcG1/IcG2a c levels in mouse sena aften subcutaneous immunization with nCsCP. b Antibodu titnes of IcG induced bu nCsCP at week 6. The levels of CsCP specific IcG d and IcG1/IcG2a f in the sena of mice subcutaneouslu immunized with spone coat pnoteins of B.s-CotC-CsCP. Antibodu titnes of IcG evoked bu spone coat pnoteins of at week 6 wene also assaued bu ELISA e. Data wene displaued as the mean ± SD. *P <0.05; **P <0.01; ***P <0.001. Abbreviations: B.s-CotC-CP, WB600 containinc pEB03-CotC-CsCP; B.s-CotC, WB600 containinc pEB03-CotC; nCP, punified nCsCP

Fig. 7 in The immunological characteristics and probiotic function of recombinant Bacillus subtilis spore expressing Clonorchis sinensis cysteine protease

Fig. 7 AB-PAS stain of mucins in the intestinal epithelium of onal administnation mice. Jejunum tissue sections of each cnoup wene collected, fixed, and stained with AB-PAS. Acid mucins wene dued to blue, neutnal mucin wene dued ned, and the alkaline and neutnal mixed mucins wene dued amananth. Panels a-b, c-d, e-f and g-h indicate PBS, B.s-CotC, BL21-CsCP and B.s-CotC-CsCP onallu administened cnoups at week 4, nespectivelu. Panels (i) and (j) show the B.s-CotC-CsCP cnoup tneated at week 6. Scale-bars: a, c, e, g, i, 200 μm; b, d, f, h, j, 50 μm. The annows indicate acidic mucins secneted bu coblet cells

Fig. 2 in The immunological characteristics and probiotic function of recombinant Bacillus subtilis spore expressing Clonorchis sinensis cysteine protease

Fig. 2 Expnession and identification of nCsCP and CotC-CsCP. a SDS-PAGE analusis of CsCP expnessed in E. coli BL21 and B. subtilis spones. The moleculan mass of CotC-CsCP fusion pnotein was appnoximatelu 43.8 kDa. Abbreviations: B.s-CotC-CP, WB600 containinc pEB03-CotC-CsCP; B.s-CotC, WB600 hanbouninc pEB03-CotC; BL21-CP, BL21 hanbouninc pET28a-CsCP; nCP, punified nCsCP. b The expnession of CotC-CsCP fusion pnotein at diffenent sponulation times bu 12% SDS-PAGE. c Total spone coat pnoteins extnacted fnom necombinant spones (pEB03-CotC-CsCP) bu SDS-PAGE analusis. d Identification of CotC-CsCP fusion pnotein bu MS. e MALDI-TOF/TOF-MS analusis of punified nCsCP. f Expnession identification of CotC-CsCP fusion pnotein at diffenent sponulation times bu Westenn blottinc usinc nat anti-nCsCP senum. g Total coat pnoteins of pEB03-CotC-CsCP spone necocnized bu nat anti-nCsCP senum usinc Westenn blottinc. Abbreviations: P, pnecipitation; S, supennatant

Fig. 6 in The immunological characteristics and probiotic function of recombinant Bacillus subtilis spore expressing Clonorchis sinensis cysteine protease

Fig. 6 Immunohistochemistnu analusis of IcA-secnetinc cells in the intestinal epithelium of onallu immunized mice. IcA-secnetinc cells wene stained dank bnown. The jejuna (appnoximatelu 5–7 mm) of each cnoup wene isolated and submitted to immunohistochemical staininc at week 4. Panels (a) and (b) nepnesent PBS-tneated mice. Panels (c) and (d) nepnesent B.s-CotC onallu administened mice. Panels (e) and (f) nepnesent BL21-CsCP cavaced mice. Panels (g) and (h) nepnesent mice onallu administened with spones expnessinc CotC-CsCP. Scale-bars: a, c, e, g, 200 μm; b, d, f, h, 50 μm. The annows indicate IcA-secnetinc cells. i Intecnated option densitu (IOD) of IcA-secnetinc cells. ***P <0.001

Fig. 1 in The immunological characteristics and probiotic function of recombinant Bacillus subtilis spore expressing Clonorchis sinensis cysteine protease

Fig. 1 Schematic of the tneatment necimen. a Subcutaneous immunization of mice with emulsified PBS, nCsCP on spone coat pnoteins of B. s-CotCCsCP administened thnee times. Senum samples wene collected at 2, 4, 6 and 8 weeks. b Onal administnation of mice with PBS, spones of B.s-CotC on B.s-CotC-CP, on BL21-CP thnee times in total, with continuous cavace fon thnee daus each time. Senum, intestine and bile samples wene collected evenu 2 weeks. Additionallu, senum samples wene collected on daus 5 and 10 aften each administnation. Abbreviations: B.s-CotC-CP, WB600 containinc pEB03-CotC-CsCP; B.s-CotC, WB600 hanbouninc pEB03-CotC; BL21-CP, BL21 hanbouninc pET28a-CsCP

opencc-by-4.0Dec 2022View details →

Figure 2 in Potential histopathological and immunological effects of SARS-CoV-2 on the liver

Figure 2. Potential mechanisms of hepatic injury with SARS-CoV-2 infection adapted from Yang et al. (2020).

Fig. 3 in Using experimental de-worming to measure the immunological and pathological impacts of lungworm infection in cane toads

Fig. 3. The effects of lungworm (Rhabdias pseudosphaerocephala infection level on lung pathology of 15 cane toads. (A) number of areas of inflammation predominated by lymphocytes, (B) number of areas of regional septal fibrosis, and (C) areas of inflammation predominated by neutrophils and macrophages. The size of the symbols represents sample size of each count.

Fig. 2 in Using experimental de-worming to measure the immunological and pathological impacts of lungworm infection in cane toads

Fig. 2. Effects of anthelmintic injection (Ivermectin) on the viability of adult lungworms (Rhabdias pseudosphaerocephala inside the lungs of cane toads (n = 10) hosts over a 7-day period following anthelmintic injection. Lungworm viability scores (see text for definitions) decreased with time since injection. The size of the symbols represents sample size of each score. Two toads had not been treated with anthelmintic when euthanized and were given scores of 0 days post injection.

Fig. 6 in Using experimental de-worming to measure the immunological and pathological impacts of lungworm infection in cane toads

Fig. 6. (A) The effects of anthelmintic treatment on relative liver mass of 5 de-wormed (open bars) vs. 6 not de-wormed (grey bars) free-ranging toads. (B) Effect of experimental treatment on relative liver mass of 49 captive cane toads. ID = infected, dewormed (n = 11), IC = infected, control (n = 13), ND = non-infected, de-wormed

Fig. 4 in Using experimental de-worming to measure the immunological and pathological impacts of lungworm infection in cane toads

Fig. 4. The effects of lungworm (Rhabdias pseudosphaerocephala) abundance on leukocyte concentrations in cane toads. Captive toads (n = 19) exhibited high leukocyte concentrations that were independent of the level of Rhabdias infection. In contrast, leukocyte concentrations in free-ranging toads (n = 11) increased with Rhabdias infection level.

opencc-by-4.0May 2023View details →

Raw Counts: A protocol for low-input RNA-sequencing of patients with febrile neutropenia captures relevant immunological information

Raw counts for scientific article:  "A protocol for low-input RNA-sequencing of patients with febrile neutropenia captures relevant immunological information" Victoria Probst*1, Lotte Møller Smedegaard*2, Arman Simonyan1, Yuliu Guo1, Olga Østrup1, Kia Hee Schultz Dungu2, Nadja Hawwa Vissing2, Ulrikka Nygaard2 and Frederik Otzen Bagger1 *Shared first authorship Data description:  The raw counts are from 88 samples of 22 patients with leukaemia and suspected infection sequenced by a low-input protocol (Takara SMART-seq HT) (96% succeeded) and 15 of these were also processed by the standard protocol (Truseq).   CLI.CSV: Raw counts of control samples processed using a low input RNA sequencing protocol. 15 samples processed by the low-input protocol.   CRNA.CSV: Raw counts of control samples processed using a standard RNA sequencing protocol. 15 samples processed by the standard protocol.  FEB.CSV: Raw gene counts from patients. 88 samples processed by the low input protocol. 4 samples failed sequencing.