Complement is the first line of innate immunity that recognizes and removes damaged self-material and infectious microbes. There are three pathways of complement activation - classical, lectin, and alternative. Deficiencies in complement components predispose individuals to recurrent and invasive infections. Complement plays key roles in defense against microbes through opsonization, protection against immune complexes, and priming of adaptive immunity. Therapies targeting complement may help treat infection-related diseases associated with deficiencies in complement components.

1. Complement and Infection
Complement is a central homeotic system of mammals and represents the first defense
line of innate immunity. The human complement system is the first defense line of
innate immunity aiming to maintain homeostasis by recognizing and removing
damaged or modified self-material (e.g. apoptotic and necrotic cells and their
fragments), as well as infectious foreign microbes.
Complement-related Infection
Complement activation may be initiated via one or more of three pathways: the
classical, lectin, or alternative pathways. The regulatory network of complement is
very intricate and accurate because there are a large number of zymogens, receptors
and regulators participate in the enzymatic cascade cleavages. Excessive or
insufficient activation will break the delicate balance between complement activation
and inhibition, leading to various infection-related diseases, such as recurrent
infection. There is conclusive evidence showed that septic shock, meningococcal
meningitis, primary amebic meningoencephalitis, chemotherapy-induced neutropenia
are associated with complement components.

2. When suffered from infectious diseases, individuals deficient in components are
highly predisposed to the invasion, and often evolved into recurrent infections.
Genome-wide analysis studies also point to a central role for complement in
infectious disease pathogenesis. Physiological roles of complement in infectious
diseases include:
• Defense Against Microbes
C3 is a crucial source of opsonins, which label bacteria for removal by phagocytes.
always caused In severe recurrent infections, C3 deficiency is the most common
causes, in addition, the proteins [C1, C4, mannose-binding lectin (MBL), MBL-
associated serine protease 1 (MASP1) and MASP2] referred to classical pathway or
lectin pathway are also associated with recurrent bacterial infections. Deficiencies of
alternative pathway components or the positive regulator properdin predispose to
gram-negative bacterial infections. Neisseria species, typically those causing
meningococcal meningitis or sepsis is closely related with the terminal pathway-MAC
deficiency.
• Protection Against Immune Complexes
Excessive immune complexes accumulation in capillary beds will trigger
inflammation and tissue damage, while complement will block this unhindered
aggregation. Classical pathway components C1 and fragments of C4 and C3 can mask
antigens in the immune complex and disrupt the lattice, thereby limiting growth of the
complex aggregates. When the receptors (CR1, CR3, and CR4) on phagocytic cells
bind their ligands, immune complexes will be engulfed and destroyed.
• Priming Adaptive Immunity
Microbes coated with complement activation fragments provoke markedly greater
antibody responses, for instance, C3a and C5a can enhance the activity of antigen-
presenting cells (APCs) to present antigens and stimulate T cell proliferation.
Researches revealed that CR2 on B cells can reduce the threshold for B cell receptor

3. triggering and increase the amplitude of the response through a powerful
costimulatory signal.
Fig.1 Complement during infection with a pathogen. (Merle, et al. 2015)
Complement provides numerous options for drug development as it is a proteolytic
cascade that can collaborate with antibody-mediated immune response to provide
defense against infection.
Creative Biolabs provides a series of therapeutic antibodies, inhibitors, soluble
complement regulators, as well as customized services based on the complement-
associated infection, including
• Recurrent infection
• Septic shock
• Meningococcal meningitis
• Primary amebic meningoencephalitis
• Chemotherapy-induced neutropenia

4. Our comprehensive complement platform offers a great number of complement-
related products in a rapid and cost-effective manner. If you are interested, please feel
free to contact us for more details.
Reference
1. Merle, N. S.; et al. (2015). Complement system part I–molecular mechanisms of activation and
regulation. Frontiers in immunology. 6, 262.