How Does the Complement System Protect the Body?
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.
FAQs on Complement System in Biology: Pathways and Functions
1. What is the complement system in immunology?
The complement system is a crucial part of the innate immune system. It consists of a large network of over 30 proteins, mainly produced by the liver, that circulate in the blood in an inactive state. When activated by pathogens or antibodies, these proteins work in a cascade-like manner to "complement" the action of antibodies and phagocytic cells, helping to clear microbes and damaged cells, promote inflammation, and attack the pathogen's cell membrane.
2. What are the main functions of the complement system?
The complement system performs several critical functions to protect the body from infection. The four primary functions are:
Opsonization: Complement proteins, particularly C3b, coat the surface of pathogens. This process marks the pathogens for enhanced phagocytosis by cells like macrophages and neutrophils.
Inflammation: Certain complement fragments, such as C3a and C5a, act as chemoattractants. They recruit phagocytes to the site of infection and trigger inflammation by causing mast cells to release histamine.
Cell Lysis: The terminal components of the complement cascade form a structure called the Membrane Attack Complex (MAC). This complex creates pores in the membrane of pathogens like bacteria, leading to cell lysis and death.
Clearance of Immune Complexes: The complement system helps in clearing immune complexes (antigen-antibody complexes) from the circulation, preventing them from depositing in tissues and causing damage.
3. What are the three main activation pathways of the complement system?
The complement system can be activated through three distinct pathways, all of which converge at the cleavage of the C3 protein:
Classical Pathway: This pathway is typically activated by antibodies (IgG or IgM) that have bound to an antigen on a pathogen's surface. It forms a part of the adaptive immune response.
Alternative Pathway: This pathway is part of the innate immune response and can be activated spontaneously by the direct binding of the C3 protein to microbial surfaces, without the need for antibodies.
Lectin Pathway: This pathway is also part of the innate immune response. It is initiated when mannose-binding lectin (MBL), a protein in the blood, binds to mannose residues on the surface of pathogens like bacteria and fungi.
4. What is the significance of C3 protein in the complement cascade?
The C3 protein is the most abundant and central component of the complement system. Its significance lies in its role as the converging point for all three activation pathways. When activated, C3 is cleaved into two fragments:
C3a: A small fragment that promotes inflammation.
C3b: A large fragment that is the key player in opsonization (tagging pathogens for destruction) and is essential for the amplification of the complement cascade, leading to the formation of the Membrane Attack Complex (MAC).
Without functional C3, most effector functions of the complement system are severely impaired.
5. How does the complement system differentiate between host cells and pathogens to avoid self-damage?
The complement system has sophisticated regulatory mechanisms to prevent it from attacking the body's own cells. Host cells express various membrane-bound complement control proteins that are not present on microbial surfaces. For example, proteins like CD59 (protectin) prevent the formation of the Membrane Attack Complex (MAC) on host cells. Another protein, Decay-Accelerating Factor (DAF), disrupts the C3 convertases that form on the host cell surface. These regulatory proteins ensure that the powerful destructive effects of the complement system are directed specifically against foreign invaders.
6. What is the difference between the classical and alternative pathways of complement activation?
The main difference between the classical and alternative pathways lies in their activation trigger. The classical pathway is part of the adaptive immune response and is primarily activated by antigen-antibody complexes. In contrast, the alternative pathway is a component of the innate immune system and can be activated spontaneously and directly on microbial surfaces, even without antibodies, serving as a first-line defence. While their triggers differ, both pathways converge on the cleavage of C3 to activate downstream effector functions.
7. What is the Membrane Attack Complex (MAC) and how does it destroy pathogens?
The Membrane Attack Complex (MAC) is the final product of the complement cascade, formed by proteins C5b, C6, C7, C8, and multiple C9 molecules. This complex inserts itself into the membrane of a pathogen. The C9 molecules form a channel or pore, which disrupts the membrane's integrity. This leads to an uncontrolled influx of water and ions, causing the cell to swell and burst (lysis), thereby killing the pathogen.
8. What happens if there is a deficiency in the complement system?
A deficiency in complement proteins can lead to significant health issues. The consequences depend on the affected protein:
Deficiencies in early components (C1, C4, C2) are often linked to autoimmune diseases like lupus due to impaired clearance of immune complexes.
A deficiency in the central protein C3 is very serious, leading to recurrent and severe bacterial infections because key immune functions are compromised.
Deficiencies in the terminal MAC components (C5-C9) increase susceptibility to infections by certain bacteria, particularly Neisseria species.
