Previous reports indicate that anti-tumor activity arising from systemically injected P. acnes is macrophage-mediated, whereas anti-tumor activity arising from locally injected P. acnes is T cell-mediated. It is possible these P. acnes-induced cytotoxic T cells arise via the Interleukin cascade. Therefore, this study investigated the involvement of Interleukin 2 (IL 2) and Interleukin 3 (IL 3), known components of the Interleukin cascade, in local P. acnes-mediated anti-tumor action. A 500 ug dose of heat-killed stationary phase P. acnes given simultaneously with 10⁴ tumor cells was found to inhibit tumor formation completely, therefore this amount was used as a standard dose throughout the study. Unvaccinated counterparts developed palpable tumors two weeks after tumor cell administration. Lower doses of vaccine protected animals from tumor growth to a lesser degree. A vaccine prepared from logarithmic phase P. acnes exerted a moderate anti-tumor effect in some cases. IL 2 and IL 3 levels were measured in vitro in normal BALB/c mice (N), tumor-bearing mice (TBH), normal vaccinated mice (N+V), and mice receiving both tumor cell and vaccine injection (T+V). IL 2 and IL 3 production was maintained in both N and N+V host splenocyte cultures throughout the study. In a similar fashion, levels of IL 2 and IL 3 in T+V host splenocyte cultures were comparable to those of N+V hosts. However, TBH splenocyte production of IL 2 and IL 3 began to decline when tumors became palpable, at Day 14 after tumor cell inoculation. By Day 28, TBH IL 2 and IL 3 levels were <15% of normal control levels. Causes for this suppression of IL 2 and IL 3 production in TBH were examined. From reports of others it appeared that suppression may be mediated through prostaglandin(s). Addition of the prostaglandin inhibitor indomethacin to splenocyte cultures greatly enhanced IL 2 production by N, N+V and T+V splenocytes, but failed to restore IL 2 production in TBH splenocyte cultures to normal levels. Thus, it appeared prostaglandins were not directly responsible for the majority of suppression seen in TBH. In the non-tumor-burdened host, prostaglandin appeared to play a homeostatic role regarding IL 2 production. Indomethacin-treatment had little effect on IL 3 production. Nylon wool fractionation of N, TBH, N+V and T+V splenocytes suggested a cell removed by nylon wool treatment was largely responsible for the suppression of IL 2 and IL 3 production in TBH. No obvious presence of functional suppressor cells was noted in N, N+V or T+V splenocytes. From these results, it appeared that P. acnes administration maintains and/or restores IL 2 and IL 3 production, thus favoring the production of CTL. In addition, the suppression of IL 2 and IL 3 production seen in TBH may be due to a nylon wool adherent suppressor cell. A model describing the effect of P. acnes administration on local anti-tumor activity was presented. / Master of Science

Call number: LD2668 .T4 1985 G733 / Master of Science

Thesis (PhD) -- Stellenbosch University, 2002. / ENGLISH ABSTRACT: Children and adults may differ in their immune function. An adequate function of the individual's immune system is crucial to the risk for development of tuberculosis (TB) after infection with Mycobacterium tuberculosis (Mtb). Epidemiological evidence suggests an age-related incidence of TB. Furthermore, the prevailing clinical expression t ' of TB varies between age groups. -The aims of this study were to characterise the cellular immune response at different ages in TB patients and healthy individuals living in a region highly endemic for TB and to relate the findings to the clinical expression of TB in different age groups. A total of 150 persons of different ages were included in this study: 50 TB patients, (identified on the basis of clinical, radiological and microbiological characteristics), 49 healthy Mantoux positive (~15mm) and 51 healthy Mantoux negative (<15mm) subjects. All patients <12yrs were identified as having primary TB and postprimary TB was only diagnosed in patients ~12yrs. Haematologic indices were obtained from all the included subjects and found to be agerelated. With the exception of the absolute lymphocyte counts, all indices were significantly different in TB patients when compared to healthy controls. Whole blood was cultured and stimulated with PHA, PPD and ESAT -6 to measure lymphocyte proliferation and IFN-y, TNF-a, IL-2 and IL-10 production in the supernatants of the cultures. After stimulation with PHA, the production of IFN-y, TNF-a and IL-10 as well as lymphocyte proliferation were all age-related. After stimulation with PPD, age correlated positively with IFN-y production in healthy Mantoux positive subjects< 12yrs. In the age groups <20 yrs, patients produced similar amounts of IFN-y when compared to healthy age-related Mantoux positive controls. TNF-a and IL-2 production were not different between patients and controls. In this whole blood system, measuring any of these cytokines on their own did not differentiate patients from controls at all ages. The ratio of PPD stimulated IFN-y to TNF-a production was significantly less in patients with primary TB and postprimary TB when compared to Mantoux positive controls, irrespective of age. These findings indicate that calculated ratios between several cytokines may be useful markers of disease at all ages. ESA T -6 stimulated IFN -y production did not result in any significant correlation with age, but was significantly less in healthy Mantoux positive subjects ~12 yrs when compared to healthy Mantoux positive subjects <12 yrs and TB patients of all ages. This finding suggests that a positive immune response to ESAT -6 is indicative of recent immunological contact with Mtb. Total IgE was measured in serum. In children <12 yrs these values correlated with age and were highest in healthy Mantoux positive controls, thereby not confirming any inverse correlation between IgE and TB. Age should be recognised as a significant variable in quantitative measurements of cellular immune responses. / AFRIKAANSE OPSOMMING: Die immuunsisteem van kinders en volwassenes kan verskillend wees. Die mate van immuniteit van 'n individu is deurslaggewend vir die risiko om tuberkulose (TB) na infeksie met die Mycobacterium tuberculosis (M tb) te ontwikkel. Epidemiologiese bevindings suggereer dat die insidensie van TB ouderdomgebonde mag wees. V erder verskil die voorkomende kliniese beeld van TB ook tussen ouderdomsgroepe. Die doelstellings van hierdie studie was om die sellulere immuunrespons op verskillende ouderdomme by TB-pasiente en gesonde individue wat in 'n streek met hoogs endemiese TB-insidensie woon te vergelyk. Die doel was ook om vas te stel hoe hierdie bevindings by die kliniese beeld van TB by verskillende ouderdomsgroepe inpas. Daar is l50 persone van verskillende ouderdomme in hierdie studie ingesluit: 50 TBpasiente (geidentifiseer op grond van kliniese, radiologiese en mikrobiologiese karakteristieke), 49 gesonde Mantoux -positiewe (:2':l5mm) en 5l gesonde Mantouxnegatiewe (<l5mm) persone. Alle pasiente <l2 jaar is gediagnoseer met primere TB. Postprimere TB is alleenlik gediagnoseer in pasiente :2':l2 jaar. Daar is aangetoon dat. hematologiese indekse van al die persone in hierdie studie ouderdomsverwant was. Daar was n beduidende verskil in alle indekse van TB-pasiente in vergelyking met die gesonde kontroles met die uitsondering van die absolute limfosiettellings. Kulture van volbloed is gedoen en gestimuleer met behulp van PHA, PPD en ESAT -6 om limfosiet-proliferasie, IFN-y-, TNF-a-, IL-2- en IL-l0-produksie in die supematante van die kulture te meet. Na stimulasie met PHA was die produksie van IFN-y, TNF-a en IL-l0, asook die limfosiet-proliferasie ouderdomsverwant Na stimulasie met PPD het ouderdom positief gekorreleer met IFN-y produksie in gesonde Mantoux-positiewe persone <l2 jaar. In die ouderdomsgroep <20 jaar het pasiente dieselfde hoeveelhede IFN-y geproduseer as gesonde, ouderdomsverwante Mantoux-positiewe kontroles. Daar was geen verskil tussen die produksie van TNF -a. en IL-2 tussen pasiente en kontroles nie. In hierdie volbloed-sisteem het die meet van nie een van hierdie sitokiene op sigself 'n verskil getoon tussen pasiente en kontroles van aile ouderdomme nie. Die verhouding van PPD-gestimuleerde IFN-y- tot TNF-a.-produksie was betekenisvol minder in pasiente met primere TB en postprimere TB in vergelyking met Mantouxpositiewe kontroles, ongeag ouderdom. Hierdie bevindings toon dat berekende verhoudings tussen verskillende sitokiene waardevoile merkers van 'n siektetoestand {TB) by aile ouderdomme kan wees. ESAT-6 gestimuleerde IFN-y-produksie het geen betekenisvoile korrelasie met ouderdom getoon nie. Daar was egter betekenisvol minder produksie in gesonde Mantoux-positiewe persone ~l2 jaar as in gesonde Mantoux-positiewe persone <l2 jaar, asook in vergelyking met TB-pasiente van aile ouderdomme. Hierdie bevinding kan daarop dui dat 'n positiewe immuun respons op ESAT -6 'n aanduiding van onlangse immunologiese kontak met M tb is. Totale IgE was in serum bepaal. In kinders <l2 jaar het hierdie waardes gekorreleer met ouderdomme en die waardes was die hoogste in gesonde Mantoux-positiewe kontroles. Hierdeur is daar nie bevestig dat daar 'n omgekeerde korrelasie tussen IgE en TB is nie. Ouderdom behoort dus as 'n belangrike veranderlike gesien te word in die kwantitatiewe meting van die sellulere immuunrespons.

by Stefanie P.C. Czerwinski. / Thesis (M.S.)--Florida Atlantic University, 2013. / Includes bibliography. / Mode of access: World Wide Web. / System requirements: Adobe Reader. / Sjèogren's Syndrome (SS) is a chronic, inflammatory autoimmune disease affecting mostly the exocrine cells of lacrimal and salivary glands, leading to diminished secretory function and resulting in keratoconjunctivitis sicca (dry eye disease) and/or stomatitis sicca (dry mouth disease). Despite several decades of studies focusing on autoimmune diseases and dry eye diseases, the exact etiology and mechanisms of SS remain unknown. Besides the fact that SS is often unreported, unrecognized and untreated, today's therapies rely exclusively on treating the symptoms after disease progression; there exists neither prevention therapy nor cure for SS. In addition, SS has been diagnosed predominantly in post-menopausal women with the female to male ratio reaching 9:1, suggesting a role of ovarian sex hormones in the pathogenesis of SS. However, not all postmenopausal women develop SS, indicating the contribution of other factors such as a genetic background to the onset of SS. In the present study, ovariectomized (OVX) NOD.B10.H2b mice provide a model of menopause with a genetic predisposition to SS, as compared to non-predisposed C57BL/10 mice. Both strands of mice were either sham operated, OVX, OVX and treated with 17(Sb (Bestradiol (E2), or OVX and treated with dihydrotestosterone (DHT). Lacrimal glands were collected 3, 7, 21, and 30 days after surgery and processed for RNA analysis by rt-qPCR and protein assays by ELISA to evaluate cytokine expression and concentrations of IL- 1\U+fffd\, TNF-a, IFN-(Sd(B, IL-10, and IL-4 on a timeline. Overall, our results showed a significant increase in IL-1\U+fffd\ TNF-a, IL-10, and IL-4 expression and levels in the lacrimal glands of OVX NOD.B10.H2b mice as compared to sham operated animals, and treatment with E2 or DHT at time of OVX prevented the increase in cytokine expression and levels.

The objective of this thesis was to test for associations between genetic polymorphisms of genes related to immune response (growth hormone (GH), growth hormone receptor (GHR), ornithine decarboxylase (ODC), insuline-like growth factor-1 (IGF-1), adrenocorticotropin hormone (ACTH), corticotrophin releasing hormone (CRH), and prolactin (PRL)) and mastitis resistance traits (incidence of clinical mastitis (ICM), occurrence of clinical mastitis (OCM), culling due to mastitis (CDM), and somatic cell scores (SCS)) in Canadian Holsteins. / Using lactation records of cows enrolled in milking recording in Quebec (Programme d'Analyse des Troupeaux Laitiers du Quebec, PATLQ from 1980 to 1994 (411,291 first, 238,432 second, and 130,983 third lactations, respectively) Estimated Transmitting Abilities of traits were generated with a model that included the random effect of sire, and fixed effects of herd-year-season-of calving, age at calving, and genetic group. 721 bulls which had daughters in the phenotypic data sets were genotyped for twenty polymorphisms of the above genes located on autosomes (BTA) 5, 11, 14, 19, 20, and 23. / Two types of analysis of associations were performed: analysis across-population with a model that included the fixed effect of marker and random effect of the son of grandsire, and within-family analysis with a model that included the fixed effects of the grandsire, marker nested within grandsire, and the random effect of son nested within marker and grandsire. Permutation tests were performed to reduce Type I error probability. / Significant associations were found within families for markers of IGF-1 (BTA5), ODC (BTA11), GH (BTA 19), GHR (BTA 20), and PRL (BTA 23) for ICM, OCM, CDM, and SCS in different lactations. Some of these putative quantitative trait loci (QTL) are located on BTA where other authors have reported QTL affecting SCS and udder conformation. The results from this study may contribute to efforts to dissect the genetic basis of mastitis resistance in dairy cattle.

No description available.

Bibliography: leaves 107-119.

Bibliography: leaves 107-119 / viii, 149 leaves : / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (M.D.)--University of Adelaide, Dept. of Community Medicine, 1987

[Truncated abstract] Fetal inflammatory response syndrome (FIRS) has only recently been recognised as an important cause of spontaneous preterm delivery (PTD). In addition, it has been associated with a number of other short-term and long-term adverse neonatal outcomes, including early onset neonatal sepsis, necrotising enterocolitis, periventricular leucomalacia, cerebral palsy, and bronchopulmonary dysplasia, although the causal mechanisms are unclear. The hallmark of FIRS is histologic chorioamnionitis (HCA). Mothers with HCA are often asymptomatic and it remains unclear whether elevated maternal inflammatory markers, such as C-reactive protein (CRP) and procalcitonin (PCT), are predictive of preterm birth. Furthermore neonatal inflammatory markers such as CRP, PCT, white cell count (WCC) and absolute neutrophil count (ANC), are commonly used in clinical practice to diagnose infection in the neonatal period. Although both intrauterine inflammation and FIRS may have effects on inflammatory markers for up to 10 days following delivery, the extent to which intrauterine infection and FIRS confound these diagnostic surrogates of neonatal infection is unknown. This work addressed the hypothesis that HCA is associated with inflammatory changes that may be detected in the: (a) maternal circulation at the time of delivery, (b) umbilical cord blood at delivery and (c) post-natal circulation within the first 48 hours of life. The primary aim of this study was to investigate the relationship between the presence of HCA and maternal inflammatory markers (serum CRP and PCT on the day of delivery) as well as neonatal inflammatory markers (haematological parameters, CRP and PCT up to 48 hours following delivery). ... Cord platelet counts were likely affected by platelet activation. For both intra-rater and inter-rater reproducibility, the corrected WCC, ANC and NRBC were shown to be reliable with an ICC of >0.90 for all comparisons. However, I:T ratio was poorly reproducible. HCA appears to be a minor inflammatory insult for the mother. In the majority of cases it is asymptomatic and results in minor increases in PCT and CRP levels on the day of delivery. Conversely HCA results in significant inflammatory changes in the newborn that can be seen in the cord blood. Sensitive markers of inflammation in the cord blood are significantly higher in affected infants (CRP and PCT), while less sensitive markers, such as WCC and ANC are not significantly different. This study has shown that fetal inflammation has sustained effects on CRP and haematological parameters in early neonatal life; CRP, WCC and ANC are significantly higher in newborns exposed to HCA, peaking 24 hours following delivery. These effects may confound the interpretation of common diagnostic tests for early onset neonatal sepsis. Conclusion: HCA results in mild elevations in CRP and PCT in the cord blood. Over the subsequent 24 hours CRP, WCC and ANC increase significantly in these neonates. Intrauterine exposure to HCA may influence surrogate diagnostic markers for early onset sepsis in newborn infants. Future research to investigate novel diagnostic markers, such as CD64 and soluble triggering receptor expressed on myeloid cells (TREM-1), or enhanced microbiological molecular diagnosis, will help distinguish true invasive infection from HCA-driven inflammation in the newborn infant.

Le vieillissement s’accompagne d’une altération globale des fonctions physiologiques notamment celles de l’immunité :on parle « d’immunosénescence ». Ce processus se traduit entre autre par l’installation d’un état inflammatoire chronique caractérisé par une augmentation des taux sériques de cytokines telles que l’interleukine(IL)-6 et des protéines de la phase aigüe. Cet état proinflammatoire serait incriminé dans le déclin des fonctions physiologiques, la fragilité et les syndromes gériatriques. Par ailleurs, les maladies cardiovasculaires, la dépression et l’infection chronique par le Cytomégalovirus (CMV) sont également associés à un état inflammatoire chronique. La prévalence de ces comorbidités étant importante chez les patients gériatriques, ces maladies pourraient donc contribuer à l’association observée entre marqueurs de l’inflammation et les syndromes gériatriques.<p>Les infections représentent un problème majeur en gériatrie. Les cellules du système immunitaire inné jouent un rôle important dans les défenses contre les agents pathogènes. La reconnaissance de ceux-ci par les cellules dendritiques, les macrophages ou les monocytes fait intervenir une série de molécules telles que les récepteurs de la famille Toll (TLR). Certains travaux suggèrent que la fonction des cellules de l’immunité innée pourrait être perturbée chez les individus âgés mais ces données restent controversées.<p>Dans ce travail, nous souhaitons aborder les hypothèses suivantes :<p>•\ / Doctorat en Sciences médicales / info:eu-repo/semantics/nonPublished