Infection of C57BL/6 mice with lymphocytic choriomeningitis virus (LCMV) strain Armstrong (Arm) induces an acute infection with rapid virus clearance by CD8(+) T cells independently of CD4(+) T... Show moreInfection of C57BL/6 mice with lymphocytic choriomeningitis virus (LCMV) strain Armstrong (Arm) induces an acute infection with rapid virus clearance by CD8(+) T cells independently of CD4(+) T cell help. Residual viral antigen may, however, persist for a prolonged time. Here, we demonstrate that mice that had been transiently depleted of CD4(+) T cells during acute LCMV Arm infection generated high levels of virus-specific IgG antibodies (Ab) after viral clearance. Robust induction of LCMV-specific IgG after transient CD4(+) T cell depletion was dependent on Fc gamma receptors but not on the complement receptors CD21/CD35. In contrast to the potent production of LCMV-specific IgG, the generation of LCMV-specific isotype-switched memory B cells after transient CD4(+) T cell depletion was considerably reduced. Moreover, mice depleted of CD4(+) T cells during acute infection were strongly impaired in generating a secondary LCMV-specific B cell response upon LCMV rechallenge. In conclusion, our data indicate that LCMV antigen depots after viral clearance were capable of inducing high levels of virus-specific IgG. They failed, however, to induce robust virus-specific B cell memory revealing a previously unappreciated dichotomy of specific Ab production and memory cell formation after priming with residual antigen. Show less
Clostridium difficile is a spore-forming bacterium, the toxin-producing strains of which cause colitis. Risk factors are antibiotics, advanced age and severe comorbidity. C. difficile infection ... Show moreClostridium difficile is a spore-forming bacterium, the toxin-producing strains of which cause colitis. Risk factors are antibiotics, advanced age and severe comorbidity. C. difficile infection (CDI) has been regarded as mostly a hospital-acquired infection. Preventing relapses is considered the biggest challenge in CDI management. In this thesis, we show that CDI occurs in Dutch general practices, often in patients without contact with hospitals. Also, we show that the emerging virulent strain PCR ribotype 027 has not become dominant in European hospitals, but community-associated type 078 has become highly prevalent. Furthermore, we found that cystic fibrosis outpatients are frequently colonized with C. difficile, though mostly with nonpathogenic strains. Thus, acquisition of C. difficile in the community appears more important than previously thought. Next, we show that renal failure at the time of diagnosis predicts relapses. In addition, patients who fail to develop antibodies against C. difficile toxins have a higher chance of relapse. We describe an experimental product derived from the milk of cows vaccinated against C. difficile and its toxins, which might prevent relapses. The last part of the thesis consists of the European guideline for CDI treatment and its recent update Show less
Velzen, A.S. van; Peters, M.; Bom, J.G. van der; Fijnvandraat, K. 2014
