Anorexia nervosa (AN) affects mainly adolescent females in developed countries including the USA, Europe and Japan. The majority of patients develop AN due to abnormal eating habits resulting from a desire to be lean or fear of becoming obese after exposure to psychiatric stress. In Japan, the prevalence of AN has been increasing rapidly;[1] according to annual

reports issued by the Ministry of Health, Labour and Welfare, the incidence of eating disorders increased 10-fold in the 20 years since 1980, and the number of AN cases in particular increased fourfold during the 5 years since buy VX-809 the mid 1990s. The prevailing explanation for this increase is the change of lifestyle in Japan including the increased variety of social circumstances.

AN is associated with a number of complications including liver injury, especially elevation of the serum alanine aminotransferase (ALT) level in more than 30% of cases.[2] Furthermore, rare cases of severe liver injury resulting in acute liver failure have been reported.[3-5] However, the precise mechanism involved in the pathogenesis of liver injury associated with AN remains unclear. Moreover, few reports have documented the clinical features of AN complicated by liver injury. Some have indicated an association with low body mass index (BMI),[6, 7] although the roles of other clinical surrogate markers are unclear. The aim of the present study was to clarify the clinical features of AN complicated by liver injury and the clinical factors ABT-888 influencing hepatic complications. In clinical settings, it is important to predict the onset of severe liver injury associated with AN, which could be potentially life-threatening, and therefore it was anticipated that the information obtained from the present study would be of value to clinicians in assessing the the risk of developing this serious complication. This retrospective observation study was conducted between January 2010 and December 2011 at the Department of Gastroenterology and Department of Neuropsychiatry, Yamagata University Hospital. During this

2-year period, a total of 37 patients were admitted under a diagnosis of AN. These patients comprised both newly referred patients and established outpatients with exacerbation. There were also first admissions and repeat admissions due to deterioration of the patients’ condition. The diagnosis of AN was made by a psychiatrist in accordance with the criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) on the basis of information obtained by interview from the patients and their families. The exclusion criteria were: (i) a history of hepatic disease, (ii) established infection with hepatitis viruses (HBV or HCV), (iii) drug abuse, (iv) excessive alcohol intake, and (v) presence of autoimmune liver disease.

This may facilitate much more active lifestyles (permitting greater levels of sports and work participation) while still maintaining a low risk of bleeding. Of course, it is not known what trough level to target. Presumably the higher the trough level targeted, the less risk of bleeding and the more active the patient

can be without the worry of bleeding but with the trade-off of higher cost and more infusions [39]. With these products, patients/families may opt to minimize the number of infusions (lengthening the interval between infusions) while still maintaining the trough level of >1%, or they may opt for more frequent dosing to achieve trough levels that are substantially higher than 1%. Ultimately, some Quizartinib patients might choose one or another or a hybrid depending on their lifestyle: lengthening the interval between infusions as much as possible may be preferred

in less active children/adults, very young patients (e.g. infants) just starting on prophylaxis, and those with poor venous access. More active patients, particularly those with good venous access, might choose to receive more frequent infusions to achieve higher trough levels. All of this leads to increased individualization of prophylaxis. Until Sotrastaurin mw now, with current concentrates, it has been recommended to infuse factor in the mornings [11]. This can be quite burdensome to families who are rushing

to get their children to school and themselves to work. With longer acting factor concentrates (particularly FIXs) there may be less to gain from morning administration. As these products can be given once every 1–2 weeks (some speculate perhaps even less frequently), there may be much to gain with respect to patient adherence if the day of the week chosen to administer the factor could be a non-work/non-school day (e.g. Sunday). Longer acting concentrates may result in patients currently treated on demand now opting to be on prophylaxis. In particular, patients with severe or moderate haemophilia B who are currently treated on demand may opt to receive one prophylactic Sclareol infusion every 2–3 weeks (18–26 infusions/year). Others who are currently not on prophylaxis may choose to be on prophylaxis during certain time periods: when travelling or during particular times of the year when they might be more physically active: e.g. summer. Currently, patients not on prophylaxis (some severe and most moderate) when they travel incur the risk of bleeding and then need medical attention. Such patients with haemophilia B may, with these products, choose to receive a dose of a longer acting factor prior to travelling, which would protect them while they are away. This might greatly relieve patient/family anxiety regarding experiencing a bleed while travelling.

55) were from emergency room and 143 (38.4%) by elective surgery. There was no difference in tolerance to early enteral feeding between both groups (p = 0.945). No difference was noted in bleeding or anastomotic leak between groups (X2 0.04).

Conclusion: Some surgical schools still continue delay the early enteral feeding until a period that’s considered from security. There was no selleck chemicals evidenced that it is recommended. It’s recommended to evaluate the early enteral feeding in the patients that initiates effective peristalsis as soon as possible. Key Word(s): 1. enteral feeding; 2. bowel restitution; 3. anastomotic leak; Presenting Author: MICHAELV. CHU Additional Authors: FELIX DOMINGO JR, EILEEN PASCUA, MARICHONA NAVAL Corresponding Author: MICHAELV. CHU Affiliations: gastroenterology Objective: Nutrition is a significant factor that affects morbidity and mortality of patients with liver cirrhosis. Screening through simple bedside tools such as Subjective Global

Assessment (SGA), aids in identifying patients at risk for malnutrition. Methods: All admitted patients with liver cirrhosis during a 6 month period were included in this study. Nutritional status was assessed within 24 hours of admission using the Nutritional Risk Assessment Form (PhilSpen). Clinical and SAR245409 supplier laboratory parameters were collected prospectively. Primary outcomes were mortality and length of hospital stay. A Cox Regression Analysis was done to identify independent Pregnenolone factors for survival and longer

hospital stay. Results: A total of 114 patients with liver cirrhosis [70% (80) male, 30% (34) female] were included in the study. Prevalence of malnutrition was 68% by SGA. Nutritional risk was significantly associated with SGA (p < 0.001), ascites (p < 0.045), presence of hepatic encephalopathy either during admission or during hospital stay (p < 0.020), discharged (p < 0.006) and mortality (p < 0.005). Using multivariate analysis, Child Pugh B and High Nutritional Risk were significantly associated with reduced survival (p < 0.011, p < 0.046 respectively). Length of hospital stay was longer for each time hepatic encephalopathy developed during confinement (hazard 2.86, p < 0.042). Moderate and High Nutritional Risk were also associated with longer hospital stay (p < 0.042, p < 0.005 respectively). Conclusion: Malnutrition is significantly associated with the development of hepatic encephalopathy, mortality and length of hospital stay among patients with liver cirrhosis. On multivariate analysis, High Nutritional Risk has been shown to be an independent factor for both survival and length of hospital stay. Key Word(s): 1. malnutrition; 2. prognosis; 3.

14 In this study, we demonstrate that the interaction between HCC and stroma plays a key role in tumor progression, and that in patients this interaction occurs in more advanced disease. We based our conclusions on the following data: (1) CAFs stimulated proliferation, migration and invasion of HCC cells; (2) HCC cells secreted LPA, which promoted transdifferentiation

of PTFs to a CAF-like myofibroblastic phenotype through the up-regulation of genes related to a contractile phenotype; (3) MK-8669 in vivo this recruitment and transdifferentiation was blocked by inhibiting LPA secretion; (4) PTFs coinjected with HCC cells accelerated tumor growth and progression, but an LPA inhibitor blocked PTF transdifferentiation Buparlisib in vitro and slowed HCC growth and progression; and (5) patients with higher LPA concentrations had larger, metastatic HCC and worse survival. Myofibroblasts have recently been implicated in HCC progression,15

but the molecular mechanisms regulating the interaction between HCC and cells and myofibroblasts are still unknown. We demonstrate for the first time that LPA is involved in the reciprocal cross-talk between HCC cells and resident fibroblasts, leading to tumor progression. In particular, HCC cells activate resident fibroblasts (PTFs), which acquire a contractile capability and express α-SMA, sustained by the up-regulation of specific contractile-related genes giving rise to a myofibroblast-like phenotype. This occurs through a paracrine mechanism, because HCC cells secrete LPA and PTFs express LPA receptors that are absent in HCC cells. LPA is implicated in different malignancies and has recently been shown

to induce HCC cell invasion by increasing the production of matrix metalloproteinase-9.12 Once PTFs have assumed a myofibroblast-like phenotype, in coculture experiments they increase the proliferation, migration, and invasion of HCC cells in vitro and promote tumoral progression in vivo. We did not investigate mediators of the back cross-talk from myofibroblasts Lck toward HCC cells, but the central role of LPA is further demonstrated by the fact that by blocking LPA with a pharmacological inhibitor or with ATX-silencing, the increased proliferation, migration and invasion of HCC cells is abrogated. In vivo, this is even more striking, because after treating animals with an LPA inhibitor, we found a down-regulation of the genes supporting the myofibroblast phenotype and a lower number of activated PTFs, whereas HCC progression decreased. LPA is seen to have a central role in orchestrating the tumor–stroma interaction. This finding is consistent with a previous work showing an alteration of the phospholipid in HCC, where ATX displays a crucial role in the inflammatory peritumoral reaction by interacting with the tumor necrosis factor α/nuclear factor κB pathway.

14 In this study, we demonstrate that the interaction between HCC and stroma plays a key role in tumor progression, and that in patients this interaction occurs in more advanced disease. We based our conclusions on the following data: (1) CAFs stimulated proliferation, migration and invasion of HCC cells; (2) HCC cells secreted LPA, which promoted transdifferentiation

of PTFs to a CAF-like myofibroblastic phenotype through the up-regulation of genes related to a contractile phenotype; (3) progestogen antagonist this recruitment and transdifferentiation was blocked by inhibiting LPA secretion; (4) PTFs coinjected with HCC cells accelerated tumor growth and progression, but an LPA inhibitor blocked PTF transdifferentiation selleck compound and slowed HCC growth and progression; and (5) patients with higher LPA concentrations had larger, metastatic HCC and worse survival. Myofibroblasts have recently been implicated in HCC progression,15

but the molecular mechanisms regulating the interaction between HCC and cells and myofibroblasts are still unknown. We demonstrate for the first time that LPA is involved in the reciprocal cross-talk between HCC cells and resident fibroblasts, leading to tumor progression. In particular, HCC cells activate resident fibroblasts (PTFs), which acquire a contractile capability and express α-SMA, sustained by the up-regulation of specific contractile-related genes giving rise to a myofibroblast-like phenotype. This occurs through a paracrine mechanism, because HCC cells secrete LPA and PTFs express LPA receptors that are absent in HCC cells. LPA is implicated in different malignancies and has recently been shown

to induce HCC cell invasion by increasing the production of matrix metalloproteinase-9.12 Once PTFs have assumed a myofibroblast-like phenotype, in coculture experiments they increase the proliferation, migration, and invasion of HCC cells in vitro and promote tumoral progression in vivo. We did not investigate mediators of the back cross-talk from myofibroblasts Selleck Cobimetinib toward HCC cells, but the central role of LPA is further demonstrated by the fact that by blocking LPA with a pharmacological inhibitor or with ATX-silencing, the increased proliferation, migration and invasion of HCC cells is abrogated. In vivo, this is even more striking, because after treating animals with an LPA inhibitor, we found a down-regulation of the genes supporting the myofibroblast phenotype and a lower number of activated PTFs, whereas HCC progression decreased. LPA is seen to have a central role in orchestrating the tumor–stroma interaction. This finding is consistent with a previous work showing an alteration of the phospholipid in HCC, where ATX displays a crucial role in the inflammatory peritumoral reaction by interacting with the tumor necrosis factor α/nuclear factor κB pathway.

Therefore, pathogens could be introduced by the procedure itself. Although bile was not obtained by ERCP in the study by Olsson et al., they reported previous ERCP as a risk factor for positive bile cultures.[6] After having shown the presence of pathogens in bile and portal tracts of patients with PSC, we investigated whether

PSC patients may manifest an increased Th17 response after pathogen stimulation. Here, we report that in patients with PSC, but not in patients with PBC, stimulation of PBMCs with heat-inactivated bacteria led to a marked induction of Th17 responses. There was no difference AZD6244 cost between patients’ own pathogens and standard pathogens, but it should be noted that nonpathogenic E. coli strains were not able to elicit an increase in IL-17A expression. Of note, and in line with the deleterious effects of Candida cholangitis on the progression of disease, stimulation of PBMCs with inactivated C. albicans led to the highest expression of IL-17A in up to 30% of CD4+ T cells (Fig. 3C). In addition, more Th17 cells were found to coexpress IFN-γ (Th1/Th17 cells) after Rapamycin ic50 stimulation with E. faecalis or C. albicans (Fig. 5). These cells may be especially relevant for the development of autoimmune diseases[30, 31] and for memory functions involved in the defense

against S. aureus and C. albicans.[28] IL-17A-expressing lymphocytes could be detected around bile ducts of patients with PSC. Whereas these cells can be found in other inflammatory liver diseases as well,[32] Lepirudin it is interesting to note that IL-17A receptors are expressed on biliary epithelial cells (BECs), and that upon stimulation with IL-17, BECs produce proinflammatory cytokines, such as IL-1β, IL-6, and IL-23.[33] These cytokines could, in turn, promote the

survival of Th17 cells. It is tempting to speculate that these cytokines could not only increase the survival of Th17 cells themselves,[34] but also stimulate fibroblasts to induce periductular fibrosis.[35, 36] Selective stimulation of the TLR-5 and −7 ligands, but not stimulation with other TLR ligands, also led to the induction of IL-17A in PSC, but not in the control groups. Further elucidation of signaling pathways involved may help to understand this aberrant response to pathogens. These results are reminiscent of data obtained in IBD patients, where the IL-23/Th17 axis has been reported to shape inflammatory response in the gut.[11] In children with IBD, an aberrant Th17 response to TLR stimulation and stimulation with Candida has been demonstrated previously.[37] Additionally, polymorphisms in genes relevant for the generation and maintenance of Th17 cells, such as the IL-23 receptor, were highly associated with IBD in GWAS.[38] Of note, in the patients reported on here, aberrant Th17 response was independent from the presence or absence of IBD, strongly suggesting that this is a feature of PSC itself and not the associated IBD.

Disseminated clostridial infection and gallbladder infection with gas-producing organisms may lead to air in the liver and biliary system. Elevation of serum aminotransferase enzymes are common and usually in the range of ∼100-500 U/L for AST/ALT.2, 7 Since the advent of antiviral drugs, the frequency of viral infection http://www.selleckchem.com/products/Methazolastone.html as a cause of acute elevation of serum ALT/AST after HCT has plummeted.23 An extreme rise in ALT is now mostly due to a noninfective cause such as zone 3 hepatocyte

necrosis in SOS, hypoxic hepatitis, drug-induced liver injury, or a hepatitic presentation of GVHD.23, 37 Acute hepatitis caused by HSV, varicella zoster virus (VZV), adenovirus, and hepatitis B virus can lead to fatal fulminant hepatic failure after HCT1 and Epstein-Barr virus (EBV)-lymphoproliferative disease can be rapidly progressive (Fig. 3B–F), whereas hepatic

infections caused by cytomegalovirus and hepatitis C virus are seldom severe.7 With routine use of prophylactic acyclovir or valacyclovir, acute hepatitis due to HSV and VZV is now rare23; human herpesvirus 6 (HHV-6) and HHV-8 reactivation causing hepatitis despite antiviral prophylaxis has been reported. When there is uncertainty about the cause of rising serum ALT levels, DNA blood tests for herpesviruses, adenovirus, and HBV should be performed. Transvenous measurement of the wedged hepatic venous pressure gradient and biopsy can exclude hepatocyte necrosis caused by SOS and may demonstrate a specific viral diagnosis.25, 26 Acyclovir should be started empirically, particularly if the patient presents with abdominal HCS assay complaints typical of VZV infection.39 Adenovirus hepatitis Phloretin should be suspected if the patient has concomitant pulmonary, renal, bladder, or intestinal

symptoms; the most effective treatment is cidofovir when given early.40 Detection of EBV DNA by polymerase chain reaction in patients receiving immune suppressive drugs has allowed pre-emptive therapy with anti-B cell therapy. Fulminant hepatitis B may develop during immune reconstitution in patients at risk, but can be prevented with prophylactic antiviral agents.1, 4 If severe hepatitis B reactivation does occur, usually because a diagnosis of HBV was not made prior to HCT,10 antiviral therapy should be initiated immediately. Fulminant hepatitis B has also been reported following premature discontinuation of prophylactic antiviral therapy in oncology patients. Anti-HBV drugs should be not be discontinued until 6 months after full immune reconstitution.1 All patients, particularly those with high pretransplant HBV DNA levels, should be monitored by HBV DNA and serum ALT tests following antiviral drug withdrawal. Chronic hepatitis C in HCT recipients usually results in asymptomatic elevation of ALT from days +60-120, coinciding with the tapering of immunosuppressive drugs.7 Severe HCV hepatitis has only rarely been reported; antiviral therapy for HCV is not indicated early after HCT.

There were no significant selleckchem differences

of TGF-β1 before and after splenectomy. The reason for the chronological changes in TGF-β1 levels after splenectomy is unknown because various factors including platelets may be involved in the production of TGF-β1. We also found a slightly higher number of TGF-β1 positive cells in non-tumor areas in the liver tissue of patients with HCC than in those without. Furthermore, the number of TGF-β1 positive cells significantly increased with the progression of liver fibrosis.[4, 21, 26, 42] In conclusion, splenectomy in cirrhotic patients with hepatitis may be able to improve liver fibrosis, cause beneficial immunological changes and lower the risk of carcinogenesis. It seems necessary to accumulate further cases to establish a convincing conclusion. This study was partially supported by a Health and Labor Sciences Research Grant from the Ministry of Health, Labor and Welfare Japan, regarding Research on Intractable Diseases, Portal Hemodynamic Abnormalities. “
“Background

and Aim:  Antituberculosis drugs, isoniazid and rifampicin, in combination, are known to develop drug-induced hepatotoxicity (DIH). A higher risk of DIH during antituberculosis treatment (ATT) has been reported in the Indian subcontinent compared to its Western counterparts. The role of genetic factors in a higher incidence of ATT hepatotoxicity in the Indian population is still unclear. The present study was aimed at investigating Glycogen branching enzyme the role of the N-acetyltransferase2 (NAT2) and cytochrome P4502E1 selleck kinase inhibitor (CYP2E1) gene polymorphisms in ATT hepatotoxicity. Methods:  The study population included 218 pulmonary tuberculosis patients who were started on ATT and followed

up for the occurrence of ATT-induced hepatitis. The genetic polymorphisms of the NAT2 and CYP2E1 genes were studied by polymerase chain reaction–restriction fragment length polymorphism. Results:  The occurrence of DIH was 18.8% (41/218). There was a higher prevalence of NAT2 slow-acetylator genotypes in DIH (70.73%) compared to non-DIH (44.63%; P < 0.05). The frequency of the NAT2*5/*7 and NAT2*6/*7 genotypes was significantly higher in DIH than non-DIH (19.51% vs 6.78%, and 19.51% vs 5.08%). No association of the CYP2E1 RsaI polymorphism could be demonstrated with DIH. However, the DraI C/D genotype of the CYP2E1 gene was mostly prevalent in DIH (85.37%), compared to non-DIH (64.41%) (P < 0.05). Slow-acetylator status and the CYP2E1 C/D or C/C genotype together showed a higher frequency in DIH (65.85%) compared to non-DIH (28.81%) (P < 0.0001). Conclusion:  The study demonstrates for the first time a possible association between the DraI polymorphism of the CYP2E1 gene and the risk of ATT hepatotoxicity.

05); Th1 cytokine expressions were decreased (P < 0.05), and Th2 cytokine levels were increased (P < 0.05). 3, 4-DAA also induced CD4+CD25+ T cells expression (5.88 ± 2.1 vs 11.03 ± 2.93, P < 0.05) in mice MLNs. Transfer of these cells into TNBS colitis mice resulted in the reduction of the disease activity index (DAI) and histological scores. In LPMCs isolated from human Crohn's disease, 3, 4-DAA had the see more same effect. It can inhibit the cell proliferation, decrease Th1 cytokine expressions (P < 0.05), and increase Th2 cytokine levels (P < 0.05). The percentage of CD4+CD25+ T cells were also increased (1.60 ± 0.14 vs 2.45 ± 0.50, P < 0.05). 1-MT treatment led to

opposite outcomes. 3, 4-DAA can alleviate the severity of colitis through inhibiting Th1 cells response, promoting Th2 cytokines expression and inducing CD4+CD25+ T cells expression. “
“Protease inhibitors Anti-infection Compound Library datasheet (PIs) have proven to be effective adjuncts to interferon/ribavirin treatment of hepatitis C virus

(HCV) infections. Little clinical or in vitro data exists, however, on their effectiveness for nontype 1 genotypes that predominate in Europe, the Middle East, Africa, and most of Asia. NS3 protease and NS4A genes from genotypes 1-6 were inserted into the JFH clone to generate replication-competent intergenotype chimeras. Susceptibility to PIs was determined by replication and infectivity assays. To study resistance development, chimeras were cultured in subinhibitory concentrations of PIs and mutations phenotypically characterized. Marked differences in susceptibility of different genotypes to danoprevir (ITMN-191) and telaprevir (VX-950) were observed. Genotypes 1, 4, and 6 showed median inhibitory concentration (IC50) values of 2-3 nM, >100-fold lower than genotypes 2/3/5 (250-750 nM). Telaprevir susceptibilities varied over a 4-fold range, with genotypes 1 and 2 being most susceptible and genotypes 4 and 5 most resistant.

Culture of genotypes 1-6 in PIs induced numerous mutations in the NS3 protease domain, highly variable between genotypes. Introduction of danoprevir and BILN 2061-induced Fossariinae mutations into the original clones by site-directed mutagenesis (n = 29) all conferred resistant phenotypes, with particularly large increases (1-2 log greater IC50 values) in the initially susceptible genotypes 1/4/6. Most introduced mutations and showed little or no effect on replicative fitness. Conclusion: Major differences were found between genotypes in their susceptibility and resistance development to PIs. However, equal sensitivities of genotypes 1, 4, and 6 to danoprevir and a broader efficacy range of telaprevir between genotypes than initially conceptualized provide strong evidence that PIs might be effectively used beyond their genotype 1 target group. (HEPATOLOGY 2011;) Infections with hepatitis C virus (HCV) are a major cause of chronic liver diseases, such as cirrhosis and hepatocellular carcinoma.

Polymorphisms in lectin pathway genes determine their functional activity. We assessed the relationship between these polymorphic genes and clinically significant bacterial infections, i.e., sepsis, pneumonia, and intra-abdominal infection, and mortality within the first year after OLT, in relation to major risk factors in two cohorts from different transplant centers. Single-nucleotide polymorphisms in the mannose-binding lectin gene (MBL2), the ficolin-2 gene (FCN2), and the MBL-associated serine protease gene (MASP2) of recipients and donors were determined. Recipients

receiving a donor liver in the principal cohort with polymorphisms in all three components i.e., MBL2 (XA/O; O/O), FCN2+6359T, and MASP2+371A, had a cumulative risk of an infection Bcl-2 inhibitor of 75% as compared to 18% with wild-type donor livers (P = 0.002), an observation confirmed in the second cohort (P = 0.04). In addition, a genetic (mis)match between donor and

recipient www.selleckchem.com/products/r428.html conferred a two-fold higher infection risk for each separate gene. Multivariate Cox analysis revealed a stepwise increase in infection risk with the lectin pathway gene profile of the donor (hazard ratio = 4.52; P = 8.1 × 10−6) and the donor-recipient (mis)match genotype (hazard ratio = 6.41; P = 1.9 × 10−7), independent from the other risk factors sex and antibiotic prophylaxis (hazard ratio > 1.7 and P < 0.02). Moreover, patients with a lectin pathway gene polymorphism and infection had a six-fold higher mortality Decitabine purchase (P = 0.9 × 10−8), of which 80% was infection-related. Conclusion: Donor and recipient gene polymorphisms in the lectin complement pathway are major determinants of the risk of clinically significant bacterial infection and mortality after OLT. (HEPATOLOGY 2010;) The occurrence of infectious complications is a major clinical problem after orthotopic liver transplantation (OLT).1 Immunosuppressive agents that prevent graft rejection interfere with the adaptive immune response and thereby increase the susceptibility to infections. These drugs do not affect, however,

the innate immune system that is crucial for the first line of immunological defense. Lectins, humoral pattern recognition molecules of the innate immune system, recognize pathogen-associated carbohydrate motifs on microorganisms and elicit activation of multiple processes of innate immunity. In order to execute the elimination of microorganisms, these lectins, such as mannose-binding lectin (MBL) and ficolins, cooperate with phagocytes and other humoral factors, including complement. Upon pathogen binding, both lectins activate the complement system via MBL-associated serine proteases (MASPs), leading to C3b-mediated opsonization of the microorganism followed by phagocytosis and the formation of a complement membrane attack complex that directly kills the pathogen.