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Inherited Defects in Immune Defenses Leading to Pulmonary Disease
Published in Stephen D. Litwin, Genetic Determinants of Pulmonary Disease, 2020
Among the complement components, C3 plays the most clearly demonstrable role in resistance to infection. It is involved in both classical and alternate pathways and its absence leads to defects in opsonization and phagocytosis of bacteria, in Chemotaxis, and in complement-mediated lysis. Patients with C3 deficiency of different etiologies all show repeated episodes of infections. Bacterial invaders are usually high-grade infectious pyogens [43]. In this respect such individuals mimic hypogammaglobulinemic individuals despite normal Ig values.
The Acute Phase Complement Proteins
Published in Andrzej Mackiewicz, Irving Kushner, Heinz Baumann, Acute Phase Proteins, 2020
The C3 protein is a principle source of biologically active cleavage products that mediate inflammation, solubilize and clear immune complexes, and further propogate the complement cascade, resulting in assembly of the terminal complement protein complex (the membrane attack complex, MAC) and cytolysis via the generation of discrete membrane channels. The complement effector proteins are controlled by an elaborate network of regulatory proteins, some of which also serve as cell-surface receptors for complement activation products. A detailed account of the complement effector and regulatory genes and gene products is beyond the scope of this chapter. The reader should consult relatively recent reviews.9-11
Paracoccidioidomycosis
Published in Rebecca A. Cox, Immunology of the Fungal Diseases, 2020
Beatriz Jimenez-Finkel, Angela Restrepo-Moreno
The effect of immune sera and complement on the viability of the fungus has also been investigated.42,43 It was found that hyperimmune mouse sera and sera from patients with paracoccidioidomycosis were able to kill P. brasiliensis yeast cells in the presence of complement from mice, guinea pigs, or rabbits. Sera from C5-deficient mice were, on the other hand, inactive. Concerning complement levels in patients, it has been shown that total hemolytic complement and the C7 component are both within normal ranges. However, C3 levels appeared elevated in one study44 and decreased in another.45 On these bases, the role of complement in the pathogenesis of paracoccidioidomycosis is still unclear.
The effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on ischemic stroke and the possible underlying mechanisms
Published in International Journal of Neuroscience, 2023
Yuxia Song, Hongyang Fan, XiaoJia Tang, Yuhan Luo, Peipei Liu, Yingzhu Chen
In addition, the adaptive immunity of the patient also plays an important role in antiviral activity. Depletion of CD4+ T cells is associated with reduced recruitment of lymphocytes in the lungs and reduced production of neutralizing antibodies and cytokines, leading to strong immune-mediated interstitial pneumonia and delayed viral clearance from the lungs [17]. T helper cells produce pro-inflammatory cytokines through the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) signaling pathway [18]. Interleukin (IL)-17 recruits monocytes and neutrophils to sites of infection and activates downstream cytokine and chemokine cascades producing IL-1, IL-6, IL-8, IL-21, tumor necrosis factor (TNF)-β, and monocyte chemoattractant protein-1 (MCP-1) [19]. C3a and C5a have strong pro-inflammatory effects, which can stimulate the recruitment of inflammatory cells and the activation of neutrophils [7]. The key to the pathogenesis of COVID-19 is related to the reduction of innate immune response-related antiviral effects and the increase in the production of inflammatory cytokines. The increase of inflammatory cytokines is related to a more serious prognosis [20].
Clinical features of children with anti-CFH autoantibody-associated hemolytic uremic syndrome: a report of 8 cases
Published in Renal Failure, 2022
Qian Li, Xinxin Kong, Minle Tian, Jing Wang, Zhenle Yang, Lichun Yu, Suwen Liu, Cong Wang, Xiaoyuan Wang, Shuzhen Sun
In this study, all 8 patients presented with severe hemolytic anemia, thrombocytopenia, acute kidney injury, hematuria and gross proteinuria. Extrarenal symptoms such as pancreatitis, pulmonary hemorrhage, gastrointestinal hemorrhage, and hypertension encephalopathy were also observed in these patients. Serum positivity for anti-CFH Ab was present in these 8 children, and 6 patients showed reduced serum CFH levels. Reduced serum C3 levels were shown in 8 patients. Aditi Sinha reported complement C3 levels lower than 70 mg/dl in 62.0% of aHUS children [17]. These results suggest abnormalities of the alternative complement pathway in the pathogenesis of anti-CFH Ab-associated HUS. CFH is a central regulator of the alternative pathway C3 convertase, both in the fluid phase and on cell surfaces. Nozal and Lopez-Trascasa reported that anti-CFH antibodies in aHUS can recognize the C-terminus end of factor H, prevent factor H from binding to endothelial cells, and help in the regulation of the alternative pathway [18].
The role of the alternative pathway in paroxysmal nocturnal hemoglobinuria and emerging treatments
Published in Expert Review of Clinical Pharmacology, 2022
Jong Wook Lee, Robert A. Brodsky, Jun-Ichi Nishimura, Austin G. Kulasekararaj
There are several areas for future research over the next 5 years. As already mentioned, further study on the long-term efficacy and safety of C3 inhibition is warranted. Factor B and D inhibitors should be evaluated as monotherapies or add-on therapy, including their long-term efficacy and safety as well as their effects on fatigue and HRQOL. Studies in special populations (e.g. pregnant women) are needed to fully understand the effects of these inhibitors. Finally, patients could benefit from the development of drugs with additional routes of administration (oral, subcutaneous). Ultimately, sustained and complete suppression of terminal complement is the goal of treatment, as morbidity and mortality in PNH are linked to IVH. The availability of both proximal and terminal complement inhibitors may aid clinicians in achieving this goal and provide a broad spectrum of options to select a strategy that best fits the situation of each patient while maintaining effectiveness and safety.