The Immune System and its Function
Istvan Berczi in Pituitary Function and Immunity, 2019
In addition to the selfsustained killing of certain target cells, such as cells of animals or gram-negative bacteria, certain cleavage products (C3a, C5a) exert important biological activities that include mediator release from basophilic leukocytes and mast cells (anaphylatoxins), release of hydrolytic enzymes from neutrophils, chemotactic, and phagocytosis-stimulating effects on neutrophils, eosinophils, and monocytes. These factors are capable of producing muscle contraction by acting directly on smooth muscle cells. All these effects are mediated by specific membrane receptors of the reacting cells. Recent investigations revealed that many of the complement components are produced by monocyte-macrophages, and that lymphocytes and mononuclear phagocytes are also capable of activating complement while expressing membrane receptors for the bioactive fragments. This provides for yet another amplification system of local immune reactivity, utilizing complement components that play a role in lymphocyte stimulation and the activation of mononuclear phagocytes.50 Indeed, evidence is increasing that complement fragments are involved in the regulation of immune responses.51,52 Moreover, the complement system bridges immune mediated reactions with the coagulation cascade, as well as with inflammatory reactions.53
Herpes Simplex Virus Vaccines and the Viral Strategies Used to Evade Host Immunity
Marie Studahl, Paola Cinque, Tomas Bergström in Herpes Simplex Viruses, 2017
Activation of complement occurs by one of three mechanisms: the classical, lectin, or alternative complement pathways (Fig. 1). The classical complement pathway is initiated upon the binding of antibody to the surface of pathogens or in an antibody-independent manner when C1q, the first component of the complement cascade, binds directly to targets. These targets include bacterial lipopolysaccharide, nucleic acids, polyanionic compounds, myelin, and some viruses. The lectin complement pathway recognizes mannose and N-acetyl glucosamine residues on bacteria, while the alternative complement pathway recognizes foreign surfaces. Together, these three pathways are able to recognize and activate the complement system against a diverse range of microbial pathogens.
The complement system in health and disease
Gabriel Virella in Medical Immunology, 2019
The complement system consists of approximately 30 serum and membrane-bound proteins that are found in the circulation and in tissues, most of which exist in a nonactive state. Upon activation, these complement components are rapidly converted to their active form, unleashing a potent sequential cascade leading to the formation of multiprotein membrane-spanning complexes and membrane receptor engagement of bioactive complement fragments, both of which exert substantial biological effects. Activation of the complement cascade occurs via three main activation pathways: classical, alternative, and lectin (Figure 9.1). Although the pathways of activation differ in how they are initiated, all of them generate complexes that result in the cleavage of the most abundant complement protein, C3, and as such, all pathways converge at this point.
Altered levels of complement components associated with non-immediate drug hypersensitivity reactions
Published in Journal of Immunotoxicology, 2020
Feng Wang, Liping Huang, Junfeng Yu, Dandan Zang, Liangping Ye, Qixing Zhu
In general, the complement cascade is a part of innate immunity and a key system for immune surveillance and homeostasis (Ricklin et al. 2010). The complement cascade is mostly comprised of inherent complement components, regulators, and receptors. There are three pathways for complement activation, that is, the classical, alternative, and mannose-binding lectin (MBL) pathways. All pathways lead to cleavage of C3 and formation of the membrane attack complex (C5b-9) to lyse cells (Niebuhr et al. 2012). During this process, anaphylatoxins C3a, C4a, and C5a are produced that act chemotactins for granulocytes, macrophages, and mast cells (Giraud et al. 2017; Nissila et al. 2017; Yuan et al. 2017). In normal physiological states, complement activation is tightly limited to protect host cells; this is mediated via complement factors like positive regulatory Factor B and negative regulatory Factor H (Riihila et al. 2014).
Complement inhibition as a therapeutic strategy in retinal disorders
Published in Expert Opinion on Biological Therapy, 2019
Enoch Kassa, Thomas A. Ciulla, Rehan M. Hussain, Pravin U. Dugel
The complement cascade forms a key part of the innate immune system. Normally, the complement cascade detects and acts upon infectious bacteria and cellular debris. It can be activated via an antibody-dependent pathway (the ‘classical pathway’), an antibody-independent pathway (the ‘alternate pathway’), or on binding to specific sugars on the surface of microorganisms (the ‘lectin’ pathway). Complement factor 3 (C3) is central to these complement system pathways. Activation of C3 ultimately leads to cleavage of C5 to form key terminal fragments (C5a and C5b) regardless of which pathway (classical, alternate or lectin) induced their generation. C5b is involved in the formation of membrane attack complex (MAC: C5b-9), which causes disruption of cell membranes (Figure 1) [3].
Isolation, characterisation and complement fixation activity of acidic polysaccharides from Argemone mexicana used as antimalarials in Mali
Published in Pharmaceutical Biology, 2022
Adama Dénou, Adiaratou Togola, Kari Tvete Inngjerdingen, Nastaran Moussavi, Frode Rise, Yuan Feng Zou, Dalen G. Dafam, Elijah I. Nep, Abubakar Ahmed, Taiwo E. Alemika, Drissa Diallo, Rokia Sanogo, Berit Smestad Paulsen
The complement system plays an important role in the immune defense, such as primary defense against bacterial invasions and viral infections. Complement fixating activity by polysaccharides from plants has previously been shown as an indicator of effects on the immune system (Michaelsen et al. 2000; Inngjerdingen et al. 2013; Zou et al. 2014). Recently, scientists established the effect of the complement system on parasites including Plasmodium falciparum (Kurtovic et al. 2020). The acidic polysaccharides (HMAmA1, and HMAmA2) fractionated from 100 °C water extract of A. mexicana aerial parts were tested in vitro on the complement system. Data revealed that both polymers showed complement fixation activity. The acidic polysaccharide HMAmA1 exhibited the highest activity with an ICH50 value of 5 µg/mL while the positive control BPII had an ICH50 value of 15.9 µg/mL (Table 5). These values are about three times higher compared to the positive control (BPII) (Figure 2). This fact could partly be due to their molecular weights which were not determined in this study. Previous work has shown that acidic polysaccharides with high molecular weights exhibited the most potent activities (Zou et al. 2015). In addition, these same authors found that pectin with low molecular weight and a highly branched structure can have a high complement fixation activity (Zou et al. 2015). On the other hand, RG-I and arabinogalactans could also play an important role in the complement fixation activity (Togola et al. 2008).
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