真菌感染的免疫治疗课件.pptx

1、医大05级李冬凯 200501023Immunology Forum 2008PUMC.Nosocomial infection Use of broad spectrum antibiotics Aggressive intrumentation of patientsi.v.catheters,life-sustaining procedures Opportunistic infection Immunodefient patients Iatrogenic immunosuppressionchemotherapy,immunosuppressive therapy.Table 1.R

2、ank order of nosocomial bloodstream pathogens and theassociated crude mortality among 49 hospitals throughout the USRankPathogenNo.of Isolates%Crudemortality(%)12345678910Coagulase-negative staphylococci Staphylococcus aureusEnterococci Candida species Escherichia coliKlebsiella species Enterobacter

3、 species Pseudomonas species Serratia species Viridans streptococci 3,908 1,928 1,354 934 700 662 557 542 177 173 31.9 15.7 11.1 7.6 5.7 5.4 4.5 4.4 1.4 1.4 21 25 32 40 24 27 28 33 26 23Edmond,1999.Few effective drugsAMB(Amphotericin b),Fluconazole,VoriconazoleSerious side effectsAntifungal drug res

4、istanceInvasive candidiasis diagnose:poor outcome of fungal infectionssIL-4R(recombinant soluble receptors to IL-4)anti-IL-10.CSF:Effect on cell number and functionsrGM-CSFBetter haematological responseLower fungal infection-related mortality raterG-CSFNeutrophil recoveryLower mortality and decrease

5、d fungal outgrowthrM-CSFTreatment with subacute or chronic fungal infection.Kullberg,1998.Combination:CSF+antifungal drugsFluconazole+rG-CSF,non-neutropenic,disseminated candidiasisResult:safe,lower mortality,faster resolution of infection,increased leukocyte number.OverviewCytokine-based Strategies

6、Conclusion and Prospective.Obstacles for antifungal vaccination:Patients with deep immunodepression Poor immune response or even immunological disorderRedundant immune responseVaccine inducing cell-mediated responseIl-12-IFN Th1 axisDNA vaccine.Figure 8 Il-12-IFN Th1 axis.A viable medical approachrD

7、NA tech:highly-specific AbrAb against fungal infectione.g.Mycograb in regulatory approval trackAb devoid of Fc component:work in the absence of phagocytic effectors or complementImportant implications for passive fungal vaccinationSynergize with antimucotics.Limitation from immuno-suppressed patient

8、s Cellular effectors Opsonization and complement deposition Selected protectve AbSome potential targets some form of toxicity or enzyme activity cognate adhesins biofilm formation.A novel approach combining innate and adaptive immunityGlu homopolymers in cell wallLaminarin from alga Laminariz digita

9、ta as antigenconjugated with a protein carrierCRM197Lam-CRM.Figure 9 The role of Toll-like receptors(TLRs)in host defense against invasive candidiasis.Kullberg,2004.Figure 10 A shematic representation of the cell wall composition and structure in C.albicans.Figure 11 Immunogold labelling of cell wal

10、l glucan in Canida albicans Torosantucci et al.2005.Critical for immunocompromized vaccinationHyphal growth-inhibitoryNeutralizing hyphae immunoevasion Maintain sufficient titer during immunosuppressive therapyUnbalance in the microbial flora since their wide specificity.Figure 12 Binding and in vit

11、ro hyphal growth inhibition caused in A.fumigatus by incubation with immuneserum of mice vaccinated with the Lam-CRM conjugate.Torosantucci et al.2005.OverviewCytokine-based StrategiesFungal Vaccine and Vaccination.Cytokine-based immunotherapy:Re-establishment of intact immune systemAntibody-based i

12、mmunotherapy:Effective,rapid and solo immunotherapySide effectRequirement for host immune statusPrice.Novel immunotherapy in a deeper layer:AMP(antimicrobial peptide)-basedPotential advantages and disadvantagesClinical trials Challenge:Relatively rare case,complex basal situation,budget Goal:Demonstrate&Optimization.医大05级李冬凯 200501023Immunology Forum 2008PUMC.