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Complement System

Written/Edited by Julian Pampel BSc

The complement system is part of the innate immune system and plays an important role in the host defense, inflammation, tissue regeneration and other physiological processes. Complement activation results in opsonization of pathogens and their removal by phagocytes. It also causes chemotactic attraction of phagocytes and macrophages. Furthermore, the complement system forms the terminal attack complex (MAC), a membrane channel causing osmotic lysis of the respective pathogen. While complement is not adaptable it does complement the adaptive immune system and it is also involved in B and T cell response regulation.

Activation of Complement System

Activation of complement unfolds along three different complement activation pathways depending on the nature of the pathogen: The classical pathway, the lectin pathway, and the alternative pathway. All three converge into the common terminal pathway that leads to the formation of the MAC. In addition, anaphylatoxins C3a and C5a elicit a plethora of physiological responses that range from chemoattraction to apoptosis. The complement system consists of more than 30 proteins that are either present as soluble proteins in the blood or as membrane-associated proteins. Most exist as inactive zymogens that are then sequentially cleaved and activated. The central component in all three pathways is component C3, the most abundant complement protein found in the blood. Its activation induces the formation of the activation products C3a, C3b, and C5a and ultimately the MAC. In addition to these three established pathways, it has been shown that factors such as kallikrein, plasmin, thrombin, and factor XIIa activate the complement system independently of the C3 protein.

Role of Complement System in Disease

Innate immune mechanisms including the complement system are the first line of a higher organism’s defense against infective agents coming from the external environment. Impairment of these basic mechanisms can cause a diverse spectrum of diseases. The reasons for the complement system malfunctioning may be different. They are often the result of mutations in genes encoding the complement cascade proteins or regulatory proteins.

Deficiencies of the C3 and other complement components, contribute to the emergence of recurrent bacterial, viral and fungal infections. MBL also plays a major protective role in the early stages of infection and in the control of inflammation. Its deficit is one of the most common reasons for human immunodeficiency, observed in microbial infections as well as in autoimmune diseases such as rheumatoid arthritis. On the other hand, the excessive activation of complement proteins is often discovered to be the reason for many diseases. These include e.g. autoimmune diseases, Alzheimer's syndrome, schizophrenia, atypical hemolytic-uremic syndrome, angioedema, macular degeneration, and Crohn's disease.

Complement is responsible for immune inflammatory response in adipose tissues which has been implicated in the development of obesity and can lead to tissue inflammation and eventually insulin resistance. Lack of regulation of the classical complement pathway through the deficiency in C1-inhibitor results in episodic angioedema. C1-inhibitor defiency can be hereditary or acquired, resulting in hereditary or acquired angioedema. Addtionally, deficiency in the C1q protein of the classical complement pathway can lead to development of systemic lupus erythematosus.

Immunotherapies have been developed to detect and destroy cells infected by the HIV virus via classical complement activation utilizing synthetic peptides that target conserved regions in HIV specific proteins and induce an antibody specific immune response through IgG antibodies.

In COVID-19, the SARS-CoV-2 nucleocapsid protein triggers activation of the lectin pathway of the complement system through interaction with mannose binding lectin (MBL)-associated serine protease (MASP)2. Released soluble N protein dimers interact with MASP-2, further accelerating MASP-2 activation and activation of the complement system. The positive feedback through cell lysis and release of N-protein leads to elevation of pro-inflammatory cytokines, characterized as cytokine storm.

N-protein neutralization is a promising avenue for a COVID-19 therapy, as well as the targeted inhibition of MASP-2. Suppressive effects could also be observed with anti-C5a antibody treatment.


References:

  1. Reis, Mastellos, Hajishengallis, Lambris: "New insights into the immune functions of complement." in: Nature reviews. Immunology, Vol. 19, Issue 8, pp. 503-516, (2020) (PubMed).
  2. Vandendriessche, Cambier, Proost, Marques: "Complement Receptors and Their Role in Leukocyte Recruitment and Phagocytosis." in: Frontiers in cell and developmental biology, Vol. 9, pp. 624025, (2021) (PubMed).
  • (3) Xaria X Li, et al. : "The Complement Receptor C5aR2: A" Powerful Modulator of Innate and Adaptive Immunity" in: J Immunol, (2019
  • (4) Gao T, et al. : "Highly pathogenic coronavirus N protein aggravates lung injury by MASP-2-mediated complement over-activation." in: medRxiv, (2020)
  • (4) Risitano AM, et al. : “Complement as a target in COVID-19?” in: Nature Reviews Immunology 65(12): 1337-45, (2020)

Complement System Related Proteins

Product
Source
Cat. No.
Validations
Quantity
Delivery
Source Escherichia coli (E. coli)
Cat. No. ABIN3091778
Validations
  • collections(1)
Quantity 1 mg
Delivery 30 to 35 Days
Source Escherichia coli (E. coli)
Cat. No. ABIN4371968
Validations
Quantity 50 μg
Delivery 4 Days
Source Insect Cells
Cat. No. ABIN3091707
Validations
  • collections(1)
Quantity 1 mg
Delivery 50 Days
Source Insect Cells
Cat. No. ABIN3077730
Validations
  • collections(1)
Quantity 1 mg
Delivery 70 Days
Source Insect Cells
Cat. No. ABIN3078028
Validations
  • collections(1)
Quantity 1 mg
Delivery 50 Days
Source Insect Cells
Cat. No. ABIN3091807
Validations
  • collections(1)
Quantity 1 mg
Delivery 70 Days
Source Insect Cells
Cat. No. ABIN3077789
Validations
  • collections(1)
Quantity 1 mg
Delivery 50 Days
Source Insect Cells
Cat. No. ABIN3090455
Validations
  • collections(1)
Quantity 1 mg
Delivery 50 Days
Source Insect Cells
Cat. No. ABIN3125981
Validations
  • collections(1)
Quantity 1 mg
Delivery 50 Days
Source Insect Cells
Cat. No. ABIN3090385
Validations
  • collections(1)
Quantity 1 mg
Delivery 50 Days
Source Human
Cat. No. ABIN4888419
Validations
Quantity 100 μg
Delivery 9 to 11 Days

Complement System Related Antibodies

Product
Reactivity
Clonality
Application
Cat. No.
Quantity
Reactivity Human
Clonality Polyclonal
Application IHC (p), WB
Cat. No. ABIN657704
Quantity 400 μL
Reactivity Human, Rat
Clonality Polyclonal
Application IHC (p), WB
Cat. No. ABIN2855659
Quantity 100 μL
Reactivity Human
Clonality Monoclonal
Application Coat, ELISA, IHC, StM
Cat. No. ABIN6940808
Quantity 100 μg
Reactivity Human, Mouse
Clonality Polyclonal
Application ELISA, IF (cc), IF (p), IHC (p), WB
Cat. No. ABIN727875
Quantity 100 μL
Reactivity Human
Clonality Polyclonal
Application FACS, IF, IHC (p), WB
Cat. No. ABIN390924
Quantity 400 μL
Reactivity Human
Clonality Polyclonal
Application ELISA, IHC (p), WB
Cat. No. ABIN3181728
Quantity 100 μL
Reactivity Human
Clonality Polyclonal
Application ICC, IF, IHC (p), WB
Cat. No. ABIN2856109
Quantity 100 μL
Reactivity Human
Clonality Polyclonal
Application ID, ELISA, WB
Cat. No. ABIN285285
Quantity 500 μL
Reactivity Human
Clonality Monoclonal
Application IF, IHC, StM
Cat. No. ABIN6940809
Quantity 100 μg

Complement System Related ELISA Kits

Product
Sample Type
Analytical Method
Cat. No.
Validations
Quantity
Sample Type Plasma, Serum
Analytical Method Quantitative Sandwich ELISA
Cat. No. ABIN6574234
Validations
  • (1)
  • collections(5)
Quantity 96 tests
Sample Type Cell Culture Cells, Cerebrospinal Fluid, Milk, Plasma, Saliva, Serum, Urine
Analytical Method Quantitative Sandwich ELISA
Cat. No. ABIN5564590
Validations
  • collections(1)
Quantity 96 tests
Sample Type Cell Culture Supernatant, Cell Lysate, Plasma, Serum, Tissue Homogenate
Analytical Method Quantitative Sandwich ELISA
Cat. No. ABIN6954999
Validations
  • collections(1)
Quantity 96 tests
Sample Type Plasma, Serum
Analytical Method Quantitative Sandwich ELISA
Cat. No. ABIN6955010
Validations
  • (4)
  • collections(1)
Quantity 96 tests
Sample Type Plasma, Serum, Tissue Homogenate
Analytical Method Quantitative Sandwich ELISA
Cat. No. ABIN6966018
Validations
  • collections(1)
Quantity 96 tests
Sample Type Cell Culture Supernatant, Cell Lysate, Plasma, Serum, Tissue Homogenate
Analytical Method Quantitative Sandwich ELISA
Cat. No. ABIN6955023
Validations
  • (1)
  • collections(1)
Quantity 96 tests
Sample Type Cell Culture Supernatant, Plasma, Serum
Analytical Method Quantitative Sandwich ELISA
Cat. No. ABIN6962118
Validations
  • collections(1)
Quantity 96 tests
Sample Type Plasma, Serum
Analytical Method Quantitative Sandwich ELISA
Cat. No. ABIN6730898
Validations
  • (5)
  • collections(4)
Quantity 96 tests
Sample Type Cell Culture Supernatant, Cell Lysate, Plasma, Serum, Tissue Homogenate
Analytical Method Quantitative Sandwich ELISA
Cat. No. ABIN6955038
Validations
  • (5)
  • collections(1)
Quantity 96 tests
Sample Type Plasma, Serum
Analytical Method Quantitative Sandwich ELISA
Cat. No. ABIN6955046
Validations
  • (6)
  • collections(1)
Quantity 96 tests

Classical Pathway

Lectin Pathway

Alternative Pathway

Terminal Pathway

Regulators

Extrinsic Pathway

Complement Receptors

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