The Immune System and its Function
Istvan Berczi in Pituitary Function and Immunity, 2019
Regulatory T cells (helper and suppressor) appear to have receptors for the Fc portion of various classes and subclasses of immunoglobulin. Although the function of these receptors has not been fully elucidated, it seems certain that they are involved in immunoregulation. Apparently, some T cells have receptors for complement components as well, especially for C3. The function of complement receptors is largely unknown. A peculiar receptor that is present on most human T cells is the one recognizing sheep erythrocytes (Sheep Red Blood Cells (SRBC), E receptor). Human T cells bind SRBC under proper conditions, which leads to “rosette” formation. This reaction is widely used for the routine discrimination and even for the separation of human T cells from other mononuclear cell types. T cells from other species also bind foreign erythrocytes: marmoset and pig T cells bind to SRBC, guinea pig T cells to rabbit erythrocytes, cat T cells to rodent, dog T cells to human and guinea pig, and rat T cells to guinea pig erythrocytes.
Pathogenic role of antigen-antibody complexes
Gabriel Virella in Medical Immunology, 2019
The ability to interact with complement receptors may also be an important determinant of pathogenicity. C1q, C3b, C3bi, C3c, and C3d readily associate with IC. This allows IC to bind to cells expressing the corresponding complement receptors. As mentioned previously, the binding of IC to CR1 expressed on the surface membrane of red cells facilitates their clearance for the circulation. In patients with SLE and other IC diseases, the number of CR1 on the surface of red cells is decreased, and this contributes to decreased IC clearance. This decreased CR1 expression has been claimed to be genetically determined in SLE. However, it is possible that the decrease may not be numerical, but functional. In other words, in patients with high concentrations of circulating IC, CR1 may be saturated, and this may result in the blocking of receptors by the IC, impairing IC clearance.
Complement-Mediated Lipopolysaccharide Release
Helmut Brade, Steven M. Opal, Stefanie N. Vogel, David C. Morrison in Endotoxin in Health and Disease, 2020
Some facultative intracellular pathogens not only evade complement-mediated killing but have also evolved the capacity to utilize complement receptors to gain entry into host cells. The intracellular fate of some opsonized intracellular bacterial pathogens, such as salmonellae, may be dependent on the complement receptor engaged by the organism. CR1 (CD35)-mediated binding and internalization of Salmonella is associated with intracellular survival, while CR3 (CD11b/CD 18)-mediated binding leads to bacteriolysis (75). The mechanism for the differential fates of CR1-bound versus CR3-bound bacteria is not known. However, earlier studies suggested that bacteria-phagocyte receptor interactions influence the granule constituents ultimately found in the neutrophil phagosome. When S. typhimurium were coated with IgG or C3b, radioiodinated azurophilic granule proteins were abundant in the phagosome, as were labeled FcR and C3b receptor molecules. In contrast, phagosomes containing Salmonella internalized by IgG-FcR interactions contained specific granule proteins, while bacteria opsonized with C3b failed to trigger the release of specific granule proteins into the phagosome (76).
Role of Mac-1 integrin in generation of extracellular vesicles with antibacterial capacity from neutrophilic granulocytes
Published in Journal of Extracellular Vesicles, 2020
Ákos M. Lőrincz, Balázs Bartos, Dávid Szombath, Viktória Szeifert, Csaba I. Timár, Lilla Turiák, László Drahos, Ágnes Kittel, Dániel S. Veres, Ferenc Kolonics, Attila Mócsai, Erzsébet Ligeti
To test the involvement of the two opsonin receptor types separately and independently from phagocytosis, we used relevant adhesive surfaces. Participation of Fc receptors in EV formation was investigated on immune complex surface but we did not observe significant increase of EV generation as compared to the control where Fc receptors are not activated (Figure 2(b)). In parallel experiments, we verified that neutrophils adherent to the immune complex surface were able to produce superoxide (Figure S3o), indicating that activation of the Fc receptors did take place and the lack of EV production increase was not the result of missing cell activation. Next we examined the potential role of complement receptors. On neutrophils the dominant complement receptors are CR3 and CR4, which belong to the family of β2 integrins and can be specifically activated by the complement fragment C3bi [44]. As shown in Figure 2(c), adding human PMN on a C3bi surface resulted in a significant increase in the number of detectable EVs. Thus, activation of the complement receptors is effective in EV biogenesis also in the absence of phagocytosis.
Autoimmune disorders associated with common variable immunodeficiency: prediction, diagnosis, and treatment
Published in Expert Review of Clinical Immunology, 2022
Niloufar Yazdanpanah, Nima Rezaei
Complement receptor type 2 (CR2, also known as CD21) is expressed on different immune cells. On B cells, CD21 contributes to the formation of a complex with CD19 and CD81. The complex acts as a coreceptor for the B cell receptor (BCR), which decreases the threshold of B cell activation upon stimulation [43,44]. B cells express CD21 based on their maturation stage; circulating naïve B cells and memory B cells express higher levels of CD21 compared to plasma cells [45]. A genetic defect of CD21 is associated with hypogammaglobulinemia [46]. Current data underpins that CD21low B cells derive from either memory B cells or plasma cells following chronic stimulation with extrinsic antigens [47]. CD21low B cells have shown weak proliferation through BCR signaling and demonstrated a shorter half-life compared with CD21+ B cells. Furthermore, despite representing an activated phenotype, CD21low B cells express inhibitory receptors. On the other hand, expansion of CD21low B cells was reported in autoreactive clones of immune cells [48–50]. Rakhmanov et al. described CD21low B cells as pre-activated polyclonal cells, which represent an attenuated function and are mainly localized in peripheral tissues [51]. Following provocation via CD40L, IL-2, and IL-10, CD21low B cells release higher levels of IgM in comparison with naïve B cells; high IgM level is proposed to be linked with the development of autoimmune conditions in CVID patients [14,52,53].
Pathogenesis guided therapeutic management of COVID-19: an immunological perspective
Published in International Reviews of Immunology, 2021
Ashutosh Kumar, Pranav Prasoon, Prakash S. Sekhawat, Vikas Pareek, Muneeb A. Faiq, Chiman Kumari, Ravi K. Narayan, Maheswari Kulandhasamy, Kamla Kant
Role of ‘complement system’ in mediation of innate immune response against the invading pathogens including viruses is important to mention [13]. Complements present a system of proteolytic cascade activated through PRRs. Invading pathogen gets opsonized, perforations are created in its structure through the enzymes released by the membrane attack complex (MAC), and is consequently destroyed [13]. Complements also act as a bridge between innate and adaptive immune response and induce the later for the cytotoxic action and formation of the antibodies [13]. Lymphocytes express complement receptors (CRs) which get activated through complement components. Thus, complement system presents an efficient way of pathogen clearance, however as it works through proteolysis, its damaging effect on host tissue is a strong limit [14]. There complement inhibitors are employed to keep in check over-activation of this system and maintain the homeostasis, however some pathogens, especially viruses, as a trick form unique structural proteins which over-activate complement mediated response to cause greater damage of the host tissue which will favor their dissemination [14].
Related Knowledge Centers
- Adaptive Immune System
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- Phagocytosis
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- Complement System