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Complement System

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Complement System and Its Pathways

The complement system is also termed the complement cascade. It is basically a very important part of the immune system that complements or enhances the abilities of the phagocytic cells and the antibodies to clear the damaged cells and microbes from an organism. Other functions of the complement system are to promote inflammation and attack the cell membrane of the pathogens.


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The complement system is a very important component of the innate immune system that an organism has. It is not adaptable and hence doesn’t go through any changes during the lifetime of an individual. However certain actions of the antibodies present in the immune system can result in the positive action of this particular system. Students can learn about different pathways of the complement system and also about the difference between classical and alternative pathways from this article. 

An Overview of the Complement System 

There are numerous small proteins included in the complement system. These proteins are properly synthesized by the liver and these tend to circulate in the bloodstream as certain precursors that are inactive. In case any trigger results in the stimulation of the proteases, these proteins will release the cytokines and will initiate a cascade of other cleavages. With the activation of the complement system, the phagocytes will be stimulated and will clear the damaged and foreign material. About 50 different proteins as well as the fragments of the proteins create the complement system. Some of the proteins are the cell membrane receptors and the serum proteins. 

There are three different biochemical pathways included in the activation of the complement system. These pathways are known as the classical complement pathway, the lectin pathway, and the alternative pathway. 

Overview Oof the Complement Activation Pathways 

The glycoproteins as well as the proteins that are responsible for the constitution of the complement system are properly synthesized using the hepatocytes. Also, the tissue macrophages, the epithelial cells, as well as the blood monocytes are also responsible for the production of these proteins. The three different pathways that are used for the activation of the complement system tend to generate the homologous versions of the protease known as C3-convertase.


What is the Classical Pathway of Complement System? 

The triggering of the classical pathway takes place when the C1-complex is activated. This particular complex is made with a single molecule of C1q, two molecules of C1r, along with two other molecules of C1qr2s2 or C1s. The triggering action takes place with the binding of C1q with the IgG or IgM and it is complexed with the antigens. Even a single pentametric IgM is capable of initiating the classical pathway of the complement system and about 6 IgGs are required for the same results. The action also takes place when the C1q molecule tends to bind directly with the pathogen surface. The binding action results in certain conformational changes in the molecule of C1q. Due to this, the 2 molecules of C1r are also activated. 

What is the Alternative Pathway of Complement System? 

When it comes to the alternative pathway, it is basically activated at a significantly low level. It is completely different from the classical pathway. The spontaneous hydrolysis of the C3 molecule results in the activation of this particular pathway. The hydrolysis occurs as a result of the breaking down of the internal thioester bond. Unlike other pathways, the alternative pathway doesn’t really rely on the antibodies that bind themselves to the pathogen. The C3 molecule results in the creation of C3b and it is due to the action of the convertase enzyme complex that is formed in the fluid phase. However, due to factor I and factor H being present, the C3b is mostly inactive. Also, the C3b-type C3 which is produced due to the spontaneous cleavage of the internal thioester is also inactive.


What is the Lectin Pathway of Complement System? 

The lectin complement pathway is another pathway that remains homologous to the classical pathway of complement. However, this nature is only seen in the case of opsonin which is a lectin that binds the mannose (MBL). Some other examples include the ficolins. This particular pathway is properly activated when the MBL is bound to mannose residues that are found on the surface of the pathogens. This results in the activation of the serine proteases that are associated with the MBL. Some common examples of such proteases include MASP-1 as well as MASP-2. The activation results in the splitting of C4 into C4a and C4b. Also, the C2 molecule is split into C2a and C2b. Then the binding of C2b and C4b takes place in order to create the classical convertase C3 which is seen in the classical pathway. 

The complement system can be defined as the system that regulates inside the blood as well as the tissue fluids of an organism. This system is responsible for the enhancement of the capabilities that certain antibodies tend to have in order to fight the pathogens by binding the proteins to their surfaces. Hence, it can be considered as one of the immune-boosting systems in organisms.

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FAQs on Complement System

1. What is the regulation of the complement system?

The complement system can effectively damage the host tissues. Hence, the regulation of this particular system must be taken into consideration. There are certain proteins that tend to regulate the entire complement system and these are known as the complement control proteins. The number of complement control proteins that are found in the blood plasma is significantly higher than the number of complement proteins. These control proteins tend to prevent the cells from being targeted by the proteins of the complement. One of the main examples of such proteins is CD59. It is also known as protectin. This particular protein impedes C9 polymerization during the entire process of development of the membrane attack complex.

2. What is the role of the complement system in disease?

The complement tends to have a very important role in the defense process and inflammation process against certain bacterial infections. The activation of the complement system can also take place during certain reactions related to incompatible blood transfusion. Also, it can be activated with any damage to the immune system in the case of any autoimmune diseases. Certain deficiencies in the components of the complement system can result in different diseases. For example, the deficiency of factors B and C3 can result in certain bacterial infections that are severe. Also, in the case of C1-inhibitor deficiency, there can be a case of Hereditary angioedema.

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