Immunity to Microbes: Lessons from Primary Immunodeficiencies

Impaired Opsonization with C3b and Phagocytosis ofStreptococcus pneumoniaein Sera from Subjects with Defects in the Classical Complement Pathway

“…Data obtained with human serum by using magnesium dichloride-EGTA chelation to inhibit classical pathway activity also suggest that the classical pathway has an important role in C3b opsonization and the phagocytosis of S. pneumoniae (17,19,35). Clinical data on complement-deficient subjects support these experimental data, with deficiencies affecting the classical pathway particularly associated with S. pneumoniae infections (10,28). Of 40 subjects with a homozygous deficiency of the classical pathway component C2 described in a recent report, 13 had had documented invasive S. pneumoniae infections (meningitis or septicemia) and 18 had had pneumonia (28), probably due to S. pneumoniae in many cases (32).…”

“…Complement factor interactions with S. pneumoniae were assessed using flow cytometry assays as described previously (7,48). Briefly, C3b-iC3b deposition was investigated by incubating 10 6 CFU of S. pneumoniae in 10 l of human serum (diluted to 20 or 50% in phosphate-buffered saline [PBS]) for 30 min with or without supplementation with purified C1q, C2, or bovine serum albumin (BSA) and then incubating the bacteria with a fluorescein isothiocyanate (FITC)-conjugated polyclonal goat anti-human C3 Ab (ICN) and characterizing the S. pneumoniae cells by using a FACSCalibur flow cytometer (BD Biosciences) with gating based on the analysis of at least 25,000 bacteria as described previously (7). The very large differences in results for control and C2 Ϫ/Ϫ sera were compared using the to S. pneumoniae in human serum used a flow cytometry method similar to that of the C3b deposition assays, with polyclonal sheep anti-human C4BP Ab (Abcam) and a FITC-conjugated donkey anti-goat IgG secondary Ab (Serotec) (both at a 1/300 dilution) (48).…”

The Effects of PspC on Complement-Mediated Immunity to Streptococcus pneumoniae Vary with Strain Background and Capsular Serotype

“…One important component of host immunity to S. pneumoniae is the complement system, a series of approximately 30 serum and cell surface proteins organized into three enzyme cascades termed the classical, alternative, and mannan binding lectin (MBL) pathways (44). Infection experiments using complement-deficient mice have demonstrated that both the classical and alternative pathways are important for immunity to S. pneumoniae (2,11,15,23,43), and the high incidence of S. pneumoniae infections in patients with complement deficiencies confirms the relevance of complement for preventing disease in humans (3,21). Both pathways lead to the formation of a C3 convertase that cleaves the central complement component C3, resulting in deposition of C3b on the surface of the pathogen that is further processed to iC3b.…”

Race between Retroviral Spread and CD4+T-Cell Response Determines the Outcome of Acute Friend Virus Infection

“…The importance of the CD4 ϩ T-cell response in controlling multiple pathogens is illustrated in primary (8) or acquired CD4 ϩ T-cell immunodeficiency, such as during human immunodeficiency virus (HIV) infection (18,47). Although the contribution of CD4 ϩ T cells to the control of viral infection is mediated largely through the provision of T-cell help to cytotoxic T cells and B cells, CD4 ϩ T cells have also been shown to exert antiviral activity, independently of other arms of adaptive immunity.…”