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1.
Cancer Epidemiol Biomarkers Prev ; 31(4): 715-727, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-35131885

RESUMO

BACKGROUND: The need to better understand the molecular underpinnings of the heterogeneous outcomes of patients with prostate cancer is a pressing global problem and a key research priority for Movember. To address this, the Movember Global Action Plan 1 Unique tissue microarray (GAP1-UTMA) project constructed a set of unique and richly annotated tissue microarrays (TMA) from prostate cancer samples obtained from multiple institutions across several global locations. METHODS: Three separate TMA sets were built that differ by purpose and disease state. RESULTS: The intended use of TMA1 (Primary Matched LN) is to validate biomarkers that help determine which clinically localized prostate cancers with associated lymph node metastasis have a high risk of progression to lethal castration-resistant metastatic disease, and to compare molecular properties of high-risk index lesions within the prostate to regional lymph node metastases resected at the time of prostatectomy. TMA2 (Pre vs. Post ADT) was designed to address questions regarding risk of castration-resistant prostate cancer (CRPC) and response to suppression of the androgen receptor/androgen axis, and characterization of the castration-resistant phenotype. TMA3 (CRPC Met Heterogeneity)'s intended use is to assess the heterogeneity of molecular markers across different anatomic sites in lethal prostate cancer metastases. CONCLUSIONS: The GAP1-UTMA project has succeeded in combining a large set of tissue specimens from 501 patients with prostate cancer with rich clinical annotation. IMPACT: This resource is now available to the prostate cancer community as a tool for biomarker validation to address important unanswered clinical questions around disease progression and response to treatment.


Assuntos
Próstata , Neoplasias de Próstata Resistentes à Castração , Humanos , Masculino , Próstata/patologia , Prostatectomia
2.
Am J Trop Med Hyg ; 104(3): 1003-1012, 2021 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-33534758

RESUMO

Anemia is a common condition in HIV-infected children; however, its pathophysiology and the contribution of frequent causes of anemia such as iron deficiency (ID) and malaria are poorly understood. We carried out an ancillary study on the effect of HIV on anemia as part of a case-control study on risk factors of anemia among Mozambican children aged 1-59 months with documented HIV status. Of them, 390 children were admitted to the hospital with anemia (hemoglobin [Hb] < 11 g/dL), whereas 272 children without anemia (Hb ≥ 11 g/dL) were recruited in the community. We assessed differences by HIV status in the presentation of anemia etiological factors and the effect of HIV infection on the association of each factor with anemia. Among the 99 HIV-infected and 563 uninfected children included, HIV-infected anemic children had an increased risk of undernutrition (P < 0.0001), Epstein-Barr virus infection (P < 0.0001), bacteremia (P = 0.0060), a decreased risk of malaria (P < 0.0001), and a similar risk of ID (P = 0.7371) compared with anemic-uninfected children. HIV-infected children were significantly less likely to have anemia associated with Plasmodium falciparum hyperparasitemia (P = 0.0444) and had a lower prevalence of parasitemia in the bone marrow (BM) (P < 0.0001) than anemic-uninfected children. Levels of BM erythropoiesis and dyserythropoiesis were comparable between groups. These findings suggest that the pathophysiology of anemia among HIV-infected malaria-exposed children is not related to HIV-specific effects. For unclear reasons, HIV-infected children had reduced risk of malaria infection, whereas ID prevalence was comparable in HIV-infected and uninfected children, suggesting that iron supplementation recommendations should not be different in HIV-infected children.


Assuntos
Anemia/etiologia , Anemia/fisiopatologia , Comorbidade , Infecções por HIV/complicações , Deficiências de Ferro/complicações , Deficiências de Ferro/fisiopatologia , Malária/complicações , Anemia/epidemiologia , Estudos de Casos e Controles , Pré-Escolar , Feminino , Infecções por HIV/epidemiologia , Humanos , Lactente , Recém-Nascido , Malária/epidemiologia , Masculino , Moçambique/epidemiologia , Prevalência , Medição de Risco , Fatores de Risco
3.
World J Urol ; 39(2): 317-326, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31955223

RESUMO

PURPOSE: Thanks to the introduction of more sensitive/specific imaging and minimally invasive treatment techniques, the oligometastatic state in prostate cancer (PCa) has attracted the interest of the uro-oncological community. We aim to identify and analyze trials across five registries to gain insights into the directions this field is moving. METHODS: A systematic review of trials on oligometastatic PCa registered on ClinicalTrials.gov, ANZCTR, ISRCTN, Netherlands and UMIN Clinical Trials Registries was performed using the following keywords: 'prostate cancer' and 'oligo'. Data were extracted from ongoing/completed trials, with an unreported primary endpoint in a peer-reviewed journal, as of May until August, 2018. RESULTS: We identified 41 trials on oligometastatic PCa. Twenty-four trials are conducted in North America and 14 in Europe. Up to 70% are phase I or II trials and < 10% (n = 4) are in phase III. Less than 50% (n = 17) are randomized controlled trials. Oligometastases are PET detected in 25 trials. Studies on synchronous oligometastatic (n = 12; 29%) or oligorecurrent (n = 14; 34%) PCa are equally represented, the remainder focus on mixed states (n = 15; 37%). The majority (n = 39; 95%) of trials investigate local treatment options (RP: 5; RT: 9; RP ± RT: 7; metastasis-directed therapy: 28) with (72%) or without (28%) systemic treatment. The remaining two are imaging studies. Progression-free (PFS; 17/41; 41%) or overall survival (OS; 3/41; 7%) is defined as primary endpoint in half of all trials, others are 'safety/toxicity' or 'PSA response'. CONCLUSIONS: With 41 ongoing trials, there is great interest in oligometastatic PCa. Most trials address local ablative treatments both for prostate and/or metastases, typically by radiotherapy, and several attempts to determine the benefit of adding systemic therapy. The field will hopefully have definitive answers after completion of four ongoing phase III trials.


Assuntos
Neoplasias da Próstata/patologia , Neoplasias da Próstata/terapia , Ensaios Clínicos como Assunto , Humanos , Masculino , Metástase Neoplásica , Recidiva Local de Neoplasia , Sistema de Registros
4.
BMC Pediatr ; 17(1): 63, 2017 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-28241813

RESUMO

BACKGROUND: Young children bear the world's highest prevalence of anaemia, the majority of which is of multifactorial aetiology, which in turn hampers its successful prevention. Even moderate degrees of anaemia are associated with increased mortality and morbidity. Despite this evidence, there is a lack of effective preventive programs and absence of consensus in the safety of iron supplementation in malaria areas, which reflects the poor understanding of the contribution of different aetiologies to anaemia. In order to reduce the anaemia burden in the most vulnerable population, a study to determine the aetiology of anaemia among pre-school Mozambican children was performed. METHODS: We undertook a case-control study of 443 preschool hospitalized children with anaemia (haemoglobin concentration <11 g/dl) and 289 community controls without anaemia. Inclusion criteria were: age 1-59 months, no blood transfusion in the previous month, residence in the study area and signed informed consent. Both univariable and multivariable logistic regression analyses were performed to identify factors associated with anaemia and adjusted attributable fractions (AAF) were estimated when appropriate. RESULTS: Malaria (adjusted odds ratio (AOR) = 8.39, p < 0.0001; AAF = 37%), underweight (AOR = 8.10, p < 0.0001; AAF = 43%), prealbumin deficiency (AOR = 7.11, p < 0.0001; AAF = 77%), albumin deficiency (AOR = 4.29, p = 0.0012; AAF = 30%), HIV (AOR = 5.73, p = 0.0060; AAF = 18%), and iron deficiency (AOR = 4.05, p < 0.0001; AAF = 53%) were associated with anaemia. Vitamin A deficiency and α-thalassaemia were frequent (69% and 64%, respectively in cases) but not independently related to anaemia. Bacteraemia (odds ratio (OR) = 8.49, p = 0.004), Parvovirus-B19 (OR = 6.05, p = 0.017) and Epstein-Barr virus (OR = 2.10, p = 0.0015) infections were related to anaemia only in the unadjusted analysis. Neither vitamin B12 deficiency nor intestinal parasites were associated with anaemia. Folate deficiency was not observed. CONCLUSIONS: Undernutrition, iron deficiency, malaria, and HIV are main factors related to anaemia in hospitalised Mozambican preschool children. Effective programs and strategies for the prevention and management of these conditions need to be reinforced. Specifically, prevention of iron deficiency that accounted in this study for more than half of anaemia cases would have a high impact in reducing the burden of anaemia in children living under similar conditions. However this deficiency, a common preventable and treatable condition, remains neglected by the international public health community.


Assuntos
Anemia/etiologia , Saúde da População Rural/estatística & dados numéricos , Anemia/epidemiologia , Estudos de Casos e Controles , Pré-Escolar , Feminino , Hospitalização , Humanos , Lactente , Modelos Logísticos , Masculino , Moçambique/epidemiologia , Análise Multivariada , Fatores de Risco
5.
Br J Haematol ; 164(6): 877-87, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24386973

RESUMO

There are no large-scale ex vivo studies addressing the contribution of Plasmodium falciparum in the bone marrow to anaemia. The presence of malaria parasites and haemozoin were studied in bone marrows from 290 anaemic children attending a rural hospital in Mozambique. Peripheral blood infections were determined by microscopy and polymerase chain reactions. Bone marrow parasitaemia, haemozoin and dyserythropoiesis were microscopically assessed. Forty-two percent (123/290) of children had parasites in the bone marrow and 49% (111/226) had haemozoin, overlapping with parasitaemia in 83% (92/111) of cases. Sexual and mature asexual parasites were highly prevalent (62% gametocytes, 71% trophozoites, 23% schizonts) suggesting their sequestration in this tissue. Sixteen percent (19/120) of children without peripheral infection had haemozoin in the bone marrow. Haemozoin in the bone marrow was independently associated with decreased Hb concentration (P = 0·005) and was more common in dyserythropoietic bone marrows (P = 0·010). The results of this ex vivo study suggest that haemozoin in the bone marrow has a role in the pathogenesis of malarial-anaemia through ineffective erythropoiesis. This finding may have clinical implications for the development of drugs targeted to prevent and treat malarial-anaemia.


Assuntos
Anemia/parasitologia , Medula Óssea/parasitologia , Hemeproteínas/metabolismo , Malária Falciparum/patologia , Plasmodium falciparum/crescimento & desenvolvimento , Adulto , Anemia/sangue , Estudos de Casos e Controles , Feminino , Humanos , Malária Falciparum/sangue , Masculino , Plasmodium falciparum/metabolismo , Adulto Jovem
6.
Blood ; 123(7): 959-66, 2014 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-24335496

RESUMO

Plasmodium falciparum immature gametocytes are not observed in peripheral blood. However, gametocyte stages in organs such as bone marrow have never been assessed by molecular techniques, which are more sensitive than optical microscopy. We quantified P falciparum sexual stages in bone marrow (n = 174) and peripheral blood (n = 70) of Mozambican anemic children by quantitative polymerase chain reaction targeting transcripts specific for early (PF14_0748; PHISTa), intermediate (PF13_0247; Pfs48/45), and mature (PF10_0303; Pfs25) gametocytes. Among children positive for the P falciparum housekeeping gene (PF08_0085; ubiquitin-conjugating enzyme gene) in bone marrow (n = 136) and peripheral blood (n = 25), prevalence of immature gametocytes was higher in bone marrow than peripheral blood (early: 95% vs 20%, P < .001; intermediate: 80% vs 16%; P < .001), as were transcript levels (P < .001 for both stages). In contrast, mature gametocytes were more prevalent (100% vs 51%, P < .001) and abundant (P < .001) in peripheral blood than in the bone marrow. Severe anemia (3.57, 95% confidence interval 1.49-8.53) and dyserythropoiesis (6.21, 95% confidence interval 2.24-17.25) were independently associated with a higher prevalence of mature gametocytes in bone marrow. Our results highlight the high prevalence and abundance of early sexual stages in bone marrow, as well as the relationship between hematological disturbances and gametocyte development in this tissue.


Assuntos
Medula Óssea/parasitologia , Malária Falciparum/diagnóstico , Técnicas de Diagnóstico Molecular , Plasmodium falciparum/isolamento & purificação , Adolescente , Adulto , Anemia/genética , Anemia/parasitologia , Animais , Medula Óssea/patologia , Criança , DNA de Protozoário/análise , Feminino , Humanos , Estágios do Ciclo de Vida/genética , Malária Falciparum/genética , Malária Falciparum/parasitologia , Masculino , Plasmodium falciparum/genética , Plasmodium falciparum/crescimento & desenvolvimento , Reação em Cadeia da Polimerase , Adulto Jovem
7.
Sci Transl Med ; 4(135): 135ra64, 2012 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-22623740

RESUMO

Case fatality rates for severe malaria remain high even in the best clinical settings because antimalarial drugs act against the parasite without alleviating life-threatening inflammation. We assessed the potential for host-directed therapy of severe malaria of a new class of anti-inflammatory drugs, the innate defense regulator (IDR) peptides, based on host defense peptides. The Plasmodium berghei ANKA model of experimental cerebral malaria was adapted to use as a preclinical screen by combining late-stage intervention in established infections with advanced bioinformatic analysis of early transcriptional changes in co-regulated gene sets. Coadministration of IDR-1018 with standard first-line antimalarials increased survival of infected mice while down-regulating key inflammatory networks associated with fatality. Thus, IDR peptides provided host-directed adjunctive therapy for severe disease in combination with antimalarial treatment.


Assuntos
Antimaláricos/uso terapêutico , Peptídeos Catiônicos Antimicrobianos/uso terapêutico , Malária/tratamento farmacológico , Animais , Células Cultivadas , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Plasmodium berghei/efeitos dos fármacos , Plasmodium berghei/patogenicidade
8.
FASEB J ; 24(12): 4701-10, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20686109

RESUMO

Megakaryocytes, which mature from hematopoietic progenitors in the bone marrow, further differentiate by reorganizing their cytoplasm into long proplatelet extensions that release platelets into the circulation. The molecular mechanisms underlying this highly dynamic cytoplasmic and cytoskeletal remodeling process are only poorly understood. Here we report that sphingosine 1-phosphate receptor 4 (S1P(4)) is specifically up-regulated during the development of human megakaryocytes from progenitor cells and is expressed in mature murine megakaryocytes. Megakaryocytes generated from S1P(4)-deficient murine bone marrow showed atypical and reduced formation of proplatelets in vitro. The recovery of platelet numbers after experimental thrombocytopenia was significantly delayed in S1p4(-/-) mice. Remarkably, overexpression and stimulation of S1P(4) in human erythroleukemia HEL cells promoted endomitosis, formation of cytoplasmic extensions, and subsequent release of platelet-like particles. These observations indicate that S1P(4) is involved in shaping the terminal differentiation of megakaryocytes.


Assuntos
Plaquetas/citologia , Diferenciação Celular/fisiologia , Megacariócitos/citologia , Megacariócitos/metabolismo , Receptores de Lisoesfingolipídeo/metabolismo , Animais , Southern Blotting , Western Blotting , Células da Medula Óssea/citologia , Diferenciação Celular/genética , Linhagem Celular , Células Cultivadas , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microscopia Eletrônica de Transmissão , Glicoproteína IIb da Membrana de Plaquetas/metabolismo , Receptores de Lisoesfingolipídeo/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Trombocitopenia/genética , Trombocitopenia/metabolismo , Trombocitopenia/patologia , Trombopoetina/sangue
9.
Nucleic Acids Res ; 38(7): 2168-76, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20056656

RESUMO

A fundamental question in microarray analysis is the estimation of the number of expressed probes in different RNA samples. Negative control probes available in the latest microarray platforms, such as Illumina whole genome expression BeadChips, provide a unique opportunity to estimate the number of expressed probes without setting a threshold. A novel algorithm was proposed in this study to estimate the number of expressed probes in an RNA sample by utilizing these negative controls to measure background noise. The performance of the algorithm was demonstrated by comparing different generations of Illumina BeadChips, comparing the set of probes targeting well-characterized RefSeq NM transcripts with other probes on the array and comparing pure samples with heterogenous samples. Furthermore, hematopoietic stem cells were found to have a larger transcriptome than progenitor cells. Aire knockout medullary thymic epithelial cells were shown to have significantly less expressed probes than matched wild-type cells.


Assuntos
Algoritmos , Perfilação da Expressão Gênica/métodos , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Sondas de Oligonucleotídeos/análise , Animais , Células-Tronco Hematopoéticas/metabolismo , Camundongos , RNA Mensageiro/análise , Células-Tronco/metabolismo , Timo/metabolismo , Fatores de Transcrição/genética , Proteína AIRE
10.
J Leukoc Biol ; 87(4): 671-82, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20028772

RESUMO

T and B lymphocytes recirculate among blood, lymph, and extralymphoid tissues to ensure immune surveillance and the establishment of self-tolerance. The underlying mechanisms regulating homeostatic lymphocyte recirculation through body cavities are not fully understood. Here, we demonstrate that the homeostatic chemokine receptor CCR7 regulates homeostatic recirculation of lymphocytes through body cavities. CCR7 deficiency results in massive accumulation of CD4(+) and CD8(+) T cells and B-2 B cells in the peritoneal and pleural cavities. The increase in B-2 B and T lymphocytes is not associated with an altered maturation and/or activation status of these cells. Mechanistically, an increase in peritoneal lymphocyte numbers is caused by impaired egress of CCR7-deficient lymphocytes from body cavities. These results establish that CCR7 plays a crucial role in lymphocyte exit from the PerC.


Assuntos
Linfócitos B/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Movimento Celular/imunologia , Cavidade Peritoneal , Receptores CCR7/imunologia , Animais , Homeostase/fisiologia , Vigilância Imunológica/fisiologia , Camundongos , Camundongos Knockout , Receptores CCR7/genética , Tolerância a Antígenos Próprios/fisiologia
11.
J Leukoc Biol ; 85(3): 409-17, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19074554

RESUMO

Thymus-independent type 2 (TI-2) antigens are repetitive antigens capable of eliciting antibody responses without T cell help. They are important in the immune response against encapsulated bacteria and as a rapid first line of defense against pathogens. TI-2 antigens induce strong proliferation in extrafollicular foci. However, any germinal centers forming in response to TI-2 antigens involute synchronously 5 days after immunization. This is thought to be caused by the lack of T cell help. Surprisingly, immunization of mice deficient for the homeostatic chemokine receptor CCR7 with TI-2 antigens resulted not only in the expected, vigorous extrafollicular plasma cell response but also in persisting splenic germinal centers. This was observed for two different TI-2 antigens, heat-killed Streptococcus pneumoniae and (4-hydroxy-3-nitrophenyl)acetyl-Ficoll (NP-Ficoll). Germinal centers induced by TI-2 and thymus-dependent (TD) antigens were located in the periarteriolar area of the white pulp in CCR7 knockout mice, corresponding to the T zone of wild-type (WT) mice. The TI-2-induced germinal centers contained peripheral rings of follicular dendritic cells and unusually for TI-2-induced germinal centers, T cells. The licensing responsible for their atypical persistence did not endow TI-2-induced germinal centers with the full range of characteristics of classic germinal centers induced by TD antigens. Thus, class-switching, affinity maturation, and memory B cell generation were not increased in CCR7-deficient mice. It seems unlikely that a defect in regulatory T cell (Treg) location was responsible for the atypical persistence of TI-2-induced germinal centers, as Tregs were comparably distributed in germinal centers of CCR7-deficient and WT mice.


Assuntos
Antígenos T-Independentes/farmacologia , Centro Germinativo/imunologia , Receptores CCR7/deficiência , Animais , Antígenos de Bactérias/farmacologia , Linfócitos B , Centro Germinativo/patologia , Memória Imunológica , Contagem de Linfócitos , Camundongos , Linfócitos T Reguladores
12.
J Leukoc Biol ; 76(3): 709-18, 2004 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-15197239

RESUMO

CXC chemokine receptor (CXCR)5 and CC chemokine receptor (CCR)7 are the major chemokine receptors required for B cell homing and microenvironmental localization during antigen-independent and -dependent B cell differentiation. Here, we show markedly decreased B-1 B cell numbers in the peritoneal cavity of CXCR5-/- and CXCR5-/-CCR7-/- double-deficient mice paralleled by reduced antigen-induced phosphorylcholine-specific immunoglobulin (Ig)M responses after intraperitoneal (i.p.) administration of streptococcal antigen. CCR7-/- mice also revealed a partial reduction in peritoneal B-1 cell numbers combined with a reduced humoral response to i.p. injected bacterial antigen. However, opposite roles of CXCR5 and CCR7 were observed when the frequency of peritoneal B-2 cells was analyzed. CXCR5-/- mice almost completely lacked B-2 cells, whereas CCR7 deficiency engendered an increase in peritoneal B-2 cells. In addition, CCR7-/- mice had enhanced, splenic IgM+ plasma cell responses, whereas the extrafollicular B cell response of the CXCR5-/- mice was not significantly altered compared with wild-type controls. Thus, the two chemokine receptors exert divergent forces at multiple levels of the innate immune response. CXCR5 plays a dominant role in peritoneal B-1 B cell homing and body cavity immunity, but both chemokine receptors are needed for a proportional peritoneal B-2 cell homing and balanced development of an early splenic B cell response.


Assuntos
Subpopulações de Linfócitos B/imunologia , Infecções Bacterianas/imunologia , Quimiotaxia de Leucócito/imunologia , Imunidade Inata/imunologia , Receptores de Quimiocinas/imunologia , Receptores de Citocinas/imunologia , Animais , Antígenos de Bactérias/efeitos dos fármacos , Antígenos de Bactérias/imunologia , Subpopulações de Linfócitos B/fisiologia , Diferenciação Celular/genética , Diferenciação Celular/imunologia , Divisão Celular/genética , Divisão Celular/imunologia , Células Cultivadas , Quimiotaxia de Leucócito/genética , Imunidade Inata/genética , Imunoglobulina M/imunologia , Imunoglobulina M/metabolismo , Camundongos , Camundongos Knockout , Plasmócitos/citologia , Plasmócitos/imunologia , Receptores CCR7 , Receptores CXCR5 , Receptores de Quimiocinas/deficiência , Receptores de Quimiocinas/genética , Receptores de Citocinas/deficiência , Receptores de Citocinas/genética , Baço/citologia , Baço/imunologia
13.
J Immunol ; 171(1): 317-24, 2003 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-12817013

RESUMO

B cells and Abs play a key role in controlling the erythrocytic stage of malaria. However, little is known about the way the humoral response develops during infection. We show that Plasmodium chabaudi chabaudi causes major, but temporary changes in the distribution of leukocytes in the spleen. Despite these changes, an ordered response to infection develops, which includes vigorous extrafollicular growth of plasmablasts and germinal center formation. Early in the response, the lymphocytes in the T zone and follicles become widely spaced, and the edges of these compartments blur. This effect is maximal around the peak of parasitemia. Germinal centers are apparent by day 8, peak at day 20, and persist through day 60. Extrafollicular foci of plasmablasts are visible from day 4 and initiate a very strong plasma cell response. Initially, the plasma cells have a conventional red pulp distribution, but by day 10 they are unconventionally sited in the periarteriolar region of the white pulp. In this region they form clusters occupying part of the area normally filled by T cells. B cells are absent from the marginal zone for at least 30 days after the peak of infection, although flow cytometry shows their continued presence in the spleen throughout infection. Relatively normal splenic architecture is regained by day 60 of infection. These results show that the changes in splenic cell distribution are linked to the presence of parasites and do not seem to interfere with the development of the humoral response.


Assuntos
Subpopulações de Linfócitos B/imunologia , Subpopulações de Linfócitos B/patologia , Malária/imunologia , Malária/patologia , Plasmodium chabaudi/imunologia , Baço/imunologia , Baço/patologia , Animais , Apoptose/imunologia , Subpopulações de Linfócitos B/parasitologia , Diferenciação Celular/imunologia , Progressão da Doença , Feminino , Centro Germinativo/imunologia , Centro Germinativo/parasitologia , Centro Germinativo/patologia , Contagem de Linfócitos , Malária/parasitologia , Camundongos , Camundongos Endogâmicos C57BL , Baço/parasitologia , Esplenopatias/imunologia , Esplenopatias/parasitologia , Esplenopatias/patologia , Fatores de Tempo
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