scholarly journals Infectious diseases associated with complement deficiencies.

1991 ◽  
Vol 4 (3) ◽  
pp. 359-395 ◽  
Author(s):  
J E Figueroa ◽  
P Densen
Keyword(s):  
Infectious Diseases ◽  
Host Defense ◽  
Complement Activation ◽  
Immune Modulation ◽  
Alternative Pathway ◽  
Membrane Attack Complex ◽  
Host Cells ◽  
Microbial Pathogens ◽  
Classical Pathway ◽  
Cellular Effects

The complement system consists of both plasma and membrane proteins. The former influence the inflammatory response, immune modulation, and host defense. The latter are complement receptors, which mediate the cellular effects of complement activation, and regulatory proteins, which protect host cells from complement-mediated injury. Complement activation occurs via either the classical or the alternative pathway, which converge at the level of C3 and share a sequence of terminal components. Four aspects of the complement cascade are critical to its function and regulation: (i) activation of the classical pathway, (ii) activation of the alternative pathway, (iii) C3 convertase formation and C3 deposition, and (iv) membrane attack complex assembly and insertion. In general, mechanisms evolved by pathogenic microbes to resist the effects of complement are targeted to these four steps. Because individual complement proteins subserve unique functional activities and are activated in a sequential manner, complement deficiency states are associated with predictable defects in complement-dependent functions. These deficiency states can be grouped by which of the above four mechanisms they disrupt. They are distinguished by unique epidemiologic, clinical, and microbiologic features and are most prevalent in patients with certain rheumatologic and infectious diseases. Ethnic background and the incidence of infection are important cofactors determining this prevalence. Although complement undoubtedly plays a role in host defense against many microbial pathogens, it appears most important in protection against encapsulated bacteria, especially Neisseria meningitidis but also Streptococcus pneumoniae, Haemophilus influenzae, and, to a lesser extent, Neisseria gonorrhoeae. The availability of effective polysaccharide vaccines and antibiotics provides an immunologic and chemotherapeutic rationale for preventing and treating infection in patients with these deficiencies.

scholarly journals Infections of People with Complement Deficiencies and Patients Who Have Undergone Splenectomy

2010 ◽  
Vol 23 (4) ◽  
pp. 740-780 ◽  
Author(s):  
Sanjay Ram ◽  
Lisa A. Lewis ◽  
Peter A. Rice
Keyword(s):  
Complement Activation ◽  
Antigen Processing ◽  
Respiratory Infections ◽  
Alternative Pathway ◽  
Fluid Phase ◽  
Host Cells ◽  
Medical Attention ◽  
Classical Pathway ◽  
Complement Components ◽  
Complement Pathways

SUMMARY The complement system comprises several fluid-phase and membrane-associated proteins. Under physiological conditions, activation of the fluid-phase components of complement is maintained under tight control and complement activation occurs primarily on surfaces recognized as “nonself” in an attempt to minimize damage to bystander host cells. Membrane complement components act to limit complement activation on host cells or to facilitate uptake of antigens or microbes “tagged” with complement fragments. While this review focuses on the role of complement in infectious diseases, work over the past couple of decades has defined several important functions of complement distinct from that of combating infections. Activation of complement in the fluid phase can occur through the classical, lectin, or alternative pathway. Deficiencies of components of the classical pathway lead to the development of autoimmune disorders and predispose individuals to recurrent respiratory infections and infections caused by encapsulated organisms, including Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae. While no individual with complete mannan-binding lectin (MBL) deficiency has been identified, low MBL levels have been linked to predisposition to, or severity of, several diseases. It appears that MBL may play an important role in children, who have a relatively immature adaptive immune response. C3 is the point at which all complement pathways converge, and complete deficiency of C3 invariably leads to severe infections, including those caused by meningococci and pneumococci. Deficiencies of the alternative and terminal complement pathways result in an almost exclusive predisposition to invasive meningococcal disease. The spleen plays an important role in antigen processing and the production of antibodies. Splenic macrophages are critical in clearing opsonized encapsulated bacteria (such as pneumococci, meningococci, and Escherichia coli) and intraerythrocytic parasites such as those causing malaria and babesiosis, which explains the fulminant nature of these infections in persons with anatomic or functional asplenia. Paramount to the management of patients with complement deficiencies and asplenia is educating patients about their predisposition to infection and the importance of preventive immunizations and seeking prompt medical attention.

scholarly journals Sequence Diversity of the Trypanosoma cruzi Complement Regulatory Protein Family

2007 ◽  
Vol 76 (2) ◽  
pp. 750-758 ◽  
Author(s):  
M. Beucher ◽  
K. A. Norris
Keyword(s):  
Trypanosoma Cruzi ◽  
Complement Activation ◽  
Alternative Pathway ◽  
Regulatory Protein ◽  
Protozoan Parasite ◽  
Microbial Pathogens ◽  
Central Component ◽  
Classical Pathway ◽  
Complement Regulatory Protein ◽  
Evolutionary Pathway

ABSTRACT As a central component of innate immunity, complement activation is a critical mechanism of containment and clearance of microbial pathogens in advance of the development of acquired immunity. Several pathogens restrict complement activation through the acquisition of host proteins that regulate complement activation or through the production of their own complement regulatory molecules (M. K. Liszewski, M. K. Leung, R. Hauhart, R. M. Buller, P. Bertram, X. Wang, A. M. Rosengard, G. J. Kotwal, and J. P. Atkinson, J. Immunol. 176:3725-3734, 2006; J. Lubinski, L. Wang, D. Mastellos, A. Sahu, J. D. Lambris, and H. M. Friedman, J. Exp. Med. 190:1637-1646, 1999). The infectious stage of the protozoan parasite Trypanosoma cruzi produces a surface-anchored complement regulatory protein (CRP) that functions to inhibit alternative and classical pathway complement activation (K. A. Norris, B. Bradt, N. R. Cooper, and M. So, J. Immunol. 147:2240-2247, 1991). This study addresses the genomic complexity of the T. cruzi CRP and its relationship to the T. cruzi supergene family comprising active trans-sialidase (TS) and TS-like proteins. The TS superfamily consists of several functionally distinct subfamilies that share a characteristic sialidase domain at their amino termini. These TS families include active TS, adhesions, CRPs, and proteins of unknown functions (G. A. Cross and G. B. Takle, Annu. Rev. Microbiol. 47:385-411, 1993). A sequence comparison search of GenBank using BLASTP revealed several full-length paralogs of CRP. These proteins share significant homology at their amino termini and a strong spatial conservation of cysteine residues. Alternative pathway complement regulation was confirmed for CRP paralogs with 58% (low) and 83% (high) identity to AAB49414. CRPs are functionally similar to the microbial and mammalian proteins that regulate complement activation. Sequence alignment of mammalian complement control proteins to CRP showed that these sequences are distinct, supporting a convergent evolutionary pathway. Finally, we show that a clonal line of T. cruzi expresses multiple unique copies of CRP that are differentially recognized by patient sera.

scholarly journals Complement Activation and Formation of the Membrane Attack Complex on Serogroup B Neisseria meningitidis in the Presence or Absence of Serum Bactericidal Activity

2002 ◽  
Vol 70 (7) ◽  
pp. 3752-3758 ◽  
Author(s):  
M. Drogari-Apiranthitou ◽  
E. J. Kuijper ◽  
N. Dekker ◽  
J. Dankert
Keyword(s):  
Bactericidal Activity ◽  
Complement Activation ◽  
Alternative Pathway ◽  
Membrane Attack Complex ◽  
Fluid Phase ◽  
Normal Serum ◽  
Chimeric Antibody ◽  
Classical Pathway ◽  
Bacterial Surface ◽  
Serum Bactericidal Activity

ABSTRACT Encapsulated meningococci are complement sensitive only in the presence of bactericidal antibodies by yet-unexplored mechanisms. The objective of this study was to investigate the involvement of major bacterial surface constituents on complement activation and membrane attack complex (MAC) formation on serogroup B meningococci in the presence or absence of antibody-dependent serum bactericidal activity (SBA). The strains used were the encapsulated H44/76, five of its variants differing in capsulation and expression of the class 1 porin (PorA), and its lipopolysaccharide (LPS)-deficient isogenic mutant (LPS−) pLAK33. Two normal sera, one with high SBA (SBA+) and one with no bactericidal activity (SBA−) against H44/76 as well as an a-γ-globulinemic serum were used for sensibilization of the bacteria. C3b and iC3b deposition on H44/76, its unencapsulated variant v24, and pLAK33 was similar in SBA+ and SBA− serum, and no difference was present between the strains. MAC deposition on H44/76 was higher in SBA+ serum than in SBA− serum and the a-γ-globulinemic serum. The amounts of C3b on H44/76, v24, and pLAK33 in the a-γ-globulinemic serum were also not different, indicating immunoglobulin G (IgG)- and LPS-independent complement activation. H44/76 PorA(+) and its PorA(−) variant and the v24 PorA(+) and its PorA(−) variant incubated in SBA− serum induced comparable amounts of MAC, despite their different serum sensitivities. Complement formation on the surface of the bacteria occurred almost exclusively via the classical pathway, but the considerable amounts of Bb measured in the serum indicated alternative pathway activation in the fluid phase. We conclude that complement deposition on meningococci is, for the most part, independent of classical pathway IgG and is not influenced by the presence of PorA or LPS on the meningococcal surface. Addition of an anti-PorA chimeric antibody to the nonbactericidal normal serum, while promoting a dose-related bacterial lysis, did not influence the amounts of C3b, iC3b, and MAC formed on the bacterial surface. These findings support the hypothesis that proper MAC insertion rather than the quantity of MAC formed on the bacterial surface is of importance for efficient lysis of meningococci.

scholarly journals Complement Activation in Chromosome 13 Dementias

2002 ◽  
Vol 277 (51) ◽  
pp. 49782-49790 ◽  
Author(s):  
Agueda Rostagno ◽  
Tamas Revesz ◽  
Tammaryn Lashley ◽  
Yasushi Tomidokoro ◽  
Laura Magnotti ◽  
...  
Keyword(s):  
Complement Activation ◽  
Alternative Pathway ◽  
Membrane Attack Complex ◽  
Classical Pathway ◽  
Chromosome 13 ◽  
Chronic Inflammatory Response ◽  
General Terms ◽  
Familial Danish Dementia ◽  
Activation Products

Chromosome 13 dementias, familial British dementia (FBD) and familial Danish dementia (FDD), are associated with neurodegeneration and cerebrovascular amyloidosis, with striking neuropathological similarities to Alzheimer's disease (AD). Despite the structural differences among the amyloid subunits (ABri in FBD, ADan in FDD, and Aβ in AD), these disorders are all characterized by the presence of neurofibrillary tangles and parenchymal and vascular amyloid deposits co-localizing with markers of glial activation, suggestive of local inflammation. Proteins of the complement system and their pro-inflammatory activation products are among the inflammation markers associated with AD lesions. Immunohistochemistry of FBD and FDD brain sections demonstrated the presence of complement activation components of the classical and alternative pathways as well as the neo-epitope of the membrane attack complex. Hemolytic experiments and enzyme-linked immunosorbent assays specific for the activation products iC3b, C4d, Bb, and C5b-9 indicated that ABri and ADan are able to fully activate the complement cascade at levels comparable to those generated by Aβ1–42. ABri and ADan specifically bound C1q with high affinity and formed stable complexes in physiological conditions. Activation proceeds ∼70–75% through the classical pathway while only ∼25–30% seems to occur through the alternative pathway. The data suggest that the chronic inflammatory response generated by the amyloid peptidesin vivomight be a contributing factor for the pathogenesis of FBD and FDD and, in more general terms, to other neurodegenerative conditions.

scholarly journals Rivaroxaban Limits Complement Activation Compared to Warfarin in Antiphospholipid Syndrome Patients with Venous Thromboembolism

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2328-2328 ◽  
Author(s):  
Deepa Jayakody Arachchillage ◽  
Ian J Mackie ◽  
Maria Efthymiou ◽  
Andrew Chitolie ◽  
Beverley J Hunt ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Antiphospholipid Syndrome ◽  
Complement Activation ◽  
Research Funding ◽  
Alternative Pathway ◽  
Factor Xa ◽  
Therapeutic Modality ◽  
Classical Pathway ◽  
Activation Markers ◽  
Complement Proteins

Abstract Background Complement activation may play a role in the pathogenesis of thrombosis and other pathological processes in the antiphospholipid syndrome (APS). Since coagulation proteases, such as factor Xa, can cleave complement proteins, we investigated complement activation in thrombotic APS patients receiving rivaroxaban, a direct factor Xa inhibitor. Aims To assess markers of complement activation (C3a, C5a, terminal complement complex (SC5b-9) and Bb fragment) in patients with thrombotic APS treated with rivaroxaban or warfarin in a prospective randomised controlled trial. Methods 116 APS patients with previous venous thromboembolism, including 22 with systemic lupus erythematosus (SLE), on long-term warfarin (target INR 2.5) were studied. 59 patients remained on warfarin and 57 (11 with SLE in each group) switched to rivaroxaban (20mg daily). EDTA samples were collected at baseline (all patients on warfarin) and on day 42 (2-4 hours after the last dose of rivaroxaban in patients on rivaroxaban). 5/116 patients were excluded (samples from four patients were haemolysed and one patient withdrew from the trial after randomisation), leaving 111 (55 rivaroxaban and 56 warfarin) patients for analysis at both baseline and day 42. Samples were also collected from 55 normal controls (NC). C3a, C5a SC5b-9 and Bb fragment were assessed using ELISA assay kits (QUIDEL Corp). Results Median (95% CI) C3a, C5a, SC5b-9 and Bb fragment were 48.9 (30.1-100.2) ng/mL, 6.8 (2.2-11.8 ng/mL, 113.9 (50.5-170) ng/mL and 1.1 (0.64-1.86) µg/mL in NC, respectively. APS patients had significantly higher complement activation markers compared to NC at both time points irrespective of the anticoagulant (p<0.0001 for C3a, C5a, SC5b-9 and Bb). There were no differences in the markers between the two patient groups at baseline, or in patients remaining on warfarin at day 42 [median (95% CI) for C3a, C5a, SC5b-9 and Bb fragment levels in patient on warfarin on day 0 vs day 42 were: C3a (ng/mL) 77.2 (33.4-180.1) vs 73.6 (34.7-156), C5a (ng/mL) 10.8 (3.2-19.4) vs 10.3 (3.7-19.8), SC5b-9 (ng/mL) 203.5 (70.5-440.3) vs 214.4 (78.3-470.4) and Bb fragment (µg/mL) 1.3 (0.6-2.8) vs 1.4 (0.7-2.4)]. In 55 patients randomised to rivaroxaban, C3a, C5a and SC5b-9 decreased significantly compared with baseline values on warfarin [day 0 versus day 42: C3a (ng/mL): 82.8 (34.6-146.6) vs 64.0 (29.2-125.1), (p=0.004); C5a (ng/mL):12.0 (4.1-17.9) vs 9.0 (2.4-14.8), p=0.01; SC5b-9 (ng/mL): 201.0 (65.6-350.2) vs 171.5 (55.6-245.5), (p=0.001)]. However, Bb fragment levels were unchanged. Conclusions Complement activation occurs in APS despite anticoagulation with warfarin. Rivaroxaban decreased complement activation compared to warfarin, although levels of the markers did not normalise in the majority of patients. This action of rivaroxaban appears to occur via the classical pathway, since Bb fragment (a marker of alternative pathway activation) was unchanged. The observations in rivaroxaban-treated patients may reflect inhibition of factor Xa cleavage of complement proteins, or inhibition of its pro-inflammatory effects (and consequent complement activation). These data suggest that rivaroxaban may have an additional therapeutic modality in thrombotic APS patients by limiting complement activation. Disclosures Mackie: Volution Immuno Pharmaceuticals (Uk) Ltd: Research Funding. Cohen:Bayer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Honoraria diverted to local charity, Research Funding, Speakers Bureau.

scholarly journals Multi-organ complement deposition in COVID-19 patients

2021 ◽  
Author(s):  
Paolo Macor ◽  
Paolo Durigutto ◽  
Alessandro Mangogna ◽  
Rossana Bussani ◽  
Stefano D'Errico ◽  
...  
Keyword(s):  
Complement Activation ◽  
Alternative Pathway ◽  
Tissue Level ◽  
Spike Protein ◽  
Classical Pathway ◽  
Limited Information ◽  
Alveolar Cells ◽  
Complement Components ◽  
Alternative Pathways ◽  
Activation Products

Background: Increased levels of circulating complement activation products have been reported in COVID-19 patients, but only limited information is available on complement involvement at tissue level. The mechanisms and pathways of local complement activation remain unclear. Methods: We performed immunofluorescence analyses of autopsy specimens of lungs, kidney and liver from nine COVID-19 patients who died of acute respiratory failure. Snap-frozen samples embedded in OCT were stained with antibodies against complement components and activation products, IgG and spike protein of SARS-CoV-2. Findings: Lung deposits of C1q, C4, C3 and C5b-9 were localized in the capillaries of the interalveolar septa and on alveolar cells. IgG displayed a similar even distribution, suggesting classical pathway activation. The spike protein is a potential target of IgG, but its uneven distribution suggests that other viral and tissue molecules may be targeted by IgG. Factor B deposits were also seen in COVID-19 lungs and are consistent with activation of the alternative pathway, whereas MBL and MASP-2 were hardly detectable. Analysis of kidney and liver specimens mirrored findings observed in the lung. Complement deposits were seen on tubules and vessels of the kidney with only mild C5b-9 staining in glomeruli, and on hepatic artery and portal vein of the liver. Interpretation. Complement deposits in different organs of deceased COVID-19 patients caused by activation of the classical and alternative pathways support the multi-organ nature of the disease.

Variable Sensitivity of Oral Isolates of Eikenella Corrodens to Serum Bactericidal Activity: Role of Antibody

1988 ◽  
Vol 2 (2) ◽  
pp. 346-353 ◽  
Author(s):  
C. Chen ◽  
M.E. Wilson
Keyword(s):  
Human Serum ◽  
Host Defense ◽  
Potential Role ◽  
Reference Strain ◽  
Alternative Pathway ◽  
Immune Defense ◽  
Classical Pathway ◽  
Eikenella Corrodens ◽  
Gram Negative

Eikenella corrodens is a facultatively anaerobic Gram-negative bacterium which is among the predominant cultivable microflora of periodontal lesions characterized by loss of attachment level. In the present study, we examined the potential role of complement-mediated killing in host defense against this periodontopathic organism. Seven clinical isolates obtained from human subgingival plaque and one reference strain of E. corrodens were characterized with respect to (a) susceptibility to the bactericidal properties of pooled human serum and (b) the role of the classical and/or alternative pathway(s) of complement in effecting killing of sensitive strains. Six strains, including the reference strain, were found to be variably serum-sensitive, exhibiting 1-12.5% survival after two hr of incubation in the presence of 20% pooled human serum. The remaining two isolates were serum-resistant. Both serum-resistant and serum-sensitive strains consumed complement via the classical pathway in normal but not in hypogammaglobulinemic serum, thus ruling out an antibody-independent mechanism of classical pathway activation. Four of six serum-sensitive strains exhibited little or no loss of viability following incubation with serum depleted of the classical pathway component Clq. One strain which was resistant to killing by normal human serum was, nevertheless, highly susceptible to complement-mediated killing in the presence of rabbit immune serum. Two additional serum-sensitive strains were killed, albeit to a lesser extent, in Clq-depleted serum, indicative of a role of the alternative pathway in killing of some serum-sensitive strains. These results indicate a potential role for complement-mediated killing in host defense against Gram-negative periodontal bacteria such as E. corrodens. However, the ultimate contribution of this immune defense mechanism may be defined, at least in part, by the presence of a humoral response to key bacterial membrane constituents.

scholarly journals Complement-dependent Clearance of Apoptotic Cells by Human Macrophages

1998 ◽  
Vol 188 (12) ◽  
pp. 2313-2320 ◽  
Author(s):  
Dror Mevorach ◽  
John O. Mascarenhas ◽  
Debra Gershov ◽  
Keith B. Elkon
Keyword(s):  
Cell Surface ◽  
Complement Activation ◽  
Apoptotic Cell ◽  
Alternative Pathway ◽  
Systemic Circulation ◽  
Classical Pathway ◽  
Apoptotic Cells ◽  
Complement Components ◽  
Serum Factors ◽  
Systemic Autoimmunity

Apoptotic cells are rapidly engulfed by phagocytes, but the receptors and ligands responsible for this phenomenon are incompletely characterized. Previously described receptors on blood- derived macrophages have been characterized in the absence of serum and show a relatively low uptake of apoptotic cells. Addition of serum to the phagocytosis assays increased the uptake of apoptotic cells by more than threefold. The serum factors responsible for enhanced uptake were identified as complement components that required activation of both the classical pathway and alternative pathway amplification loop. Exposure of phosphatidylserine on the apoptotic cell surface was partially responsible for complement activation and resulted in coating the apoptotic cell surface with C3bi. In the presence of serum, the macrophage receptors for C3bi, CR3 (CD11b/CD18) and CR4 (CD11c/CD18), were significantly more efficient in the uptake of apoptotic cells compared with previously described receptors implicated in clearance. Complement activation is likely to be required for efficient uptake of apoptotic cells within the systemic circulation, and early component deficiencies could predispose to systemic autoimmunity by enhanced exposure to and/or aberrant deposition of apoptotic cells.

Complement activation and white cell sequestration in postischemic skeletal muscle

1990 ◽  
Vol 259 (2) ◽  
pp. H525-H531
Author(s):  
B. B. Rubin ◽  
A. Smith ◽  
S. Liauw ◽  
D. Isenman ◽  
A. D. Romaschin ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Complement Activation ◽  
Alternative Pathway ◽  
Ischemia Reperfusion ◽  
White Blood Cells ◽  
Classical Pathway ◽  
Myeloperoxidase Activity ◽  
Factor B ◽  
Complement Proteins ◽  
Muscle Ischemia

After skeletal muscle ischemia, tissue damage is augmented during reperfusion. White blood cells (WBCs) and complement proteins may participate in the reperfusion injury. The purpose of this study was to define the kinetics of classical and alternative pathway complement activation and WBC sequestration by postischemic skeletal muscle during the first 48 h of reperfusion in vivo. The isolated canine gracilis muscle model was used. Systemic levels of the complement proteins factor B (alternative pathway) and C4 (classical pathway) were quantitated by hemolytic assay. WBC sequestration was measured by gracilis arterial-venous WBC differences and tissue myeloperoxidase activity. Reperfusion was associated with an 18% decrease in systemic factor B levels but no consistent change in systemic C4 levels. WBCs were sequestered during the first 4 h of reperfusion, and tissue myeloperoxidase activity was elevated 97-fold after 48 h of reperfusion. These results suggest that skeletal muscle ischemia-reperfusion stimulates 1) activation of the alternative but not the classical complement pathway and 2) an immediate and prolonged sequestration of WBCs.

scholarly journals Ectromelia Virus Inhibitor of Complement Enzymes Protects Intracellular Mature Virus and Infected Cells from Mouse Complement

2010 ◽  
Vol 84 (18) ◽  
pp. 9128-9139 ◽  
Author(s):  
Elizabeth A. Moulton ◽  
Paula Bertram ◽  
Nanhai Chen ◽  
R. Mark L. Buller ◽  
John P. Atkinson
Keyword(s):  
Immune Response ◽  
Complement Activation ◽  
Catalytic Domain ◽  
High Titer ◽  
Alternative Pathway ◽  
Classical Pathway ◽  
Ectromelia Virus ◽  
Virus Inhibitor ◽  
Infected Cells

ABSTRACT Poxviruses produce complement regulatory proteins to subvert the host's immune response. Similar to the human pathogen variola virus, ectromelia virus has a limited host range and provides a mouse model where the virus and the host's immune response have coevolved. We previously demonstrated that multiple components (C3, C4, and factor B) of the classical and alternative pathways are required to survive ectromelia virus infection. Complement's role in the innate and adaptive immune responses likely drove the evolution of a virus-encoded virulence factor that regulates complement activation. In this study, we characterized the ectromelia virus inhibitor of complement enzymes (EMICE). Recombinant EMICE regulated complement activation on the surface of CHO cells, and it protected complement-sensitive intracellular mature virions (IMV) from neutralization in vitro. It accomplished this by serving as a cofactor for the inactivation of C3b and C4b and by dissociating the catalytic domain of the classical pathway C3 convertase. Infected murine cells initiated synthesis of EMICE within 4 to 6 h postinoculation. The levels were sufficient in the supernatant to protect the IMV, upon release, from complement-mediated neutralization. EMICE on the surface of infected murine cells also reduced complement activation by the alternative pathway. In contrast, classical pathway activation by high-titer antibody overwhelmed EMICE's regulatory capacity. These results suggest that EMICE's role is early during infection when it counteracts the innate immune response. In summary, ectromelia virus produced EMICE within a few hours of an infection, and EMICE in turn decreased complement activation on IMV and infected cells.

Sign in / Sign up

Export Citation Format

Share Document