Complement- Properties and Nomenclature
The complement system is a vital part of the immune system that helps to eliminate infectious microorganisms and damaged cells from the body. It also enhances the functions of antibodies and phagocytes, which are other immune cells that recognize and destroy foreign invaders. The complement system consists of a complex network of proteins that circulate in the blood and tissues, and are activated by various triggers, such as bacteria, viruses, or antibody-antigen complexes.
The complement system has several important roles in immunity, such as:
- Causing the lysis (bursting) of cells that are infected or harmful to the body, such as bacteria, viruses, tumor cells, or transplanted organs.
- Generating mediators that stimulate inflammation, which is a protective response that attracts more immune cells to the site of infection or injury.
- Facilitating opsonization, which is a process that coats the surface of foreign particles with molecules that make them easier to be engulfed and eliminated by phagocytes.
- Causing immune clearance, which is a process that removes immune complexes (aggregates of antigens and antibodies) from the circulation and transports them to the spleen and liver for disposal.
The complement system is named so because it "complements" or enhances the ability of antibodies and phagocytes to clear microbes and damaged cells from the body. It is part of the innate immune system, which is the first line of defense against infections and does not change or adapt during an individual`s lifetime. However, the complement system can also be recruited and activated by antibodies generated by the adaptive immune system, which is the second line of defense that can recognize specific antigens and produce memory cells for future protection.
The complement system was discovered in the late 19th century by several scientists who observed that serum (the liquid part of blood) had antimicrobial activity that was lost when heated. They also found that this activity was restored when heated serum was mixed with fresh serum from an immunized animal. They called this heat-sensitive component "complement" and the heat-stable component "antibody". Later, it was found that complement consists of many different proteins that act in a cascade-like manner to produce various effects on target cells and molecules.
In this article, we will discuss the properties and nomenclature of the complement system, as well as its main effects on immunity.
Complement is a group of proteins that are involved in various immune responses. Complement has the following properties:
- Presence in various animals: Complement is found in the blood serum of all mammals, including humans, and in lower animals such as birds, amphibians, and fishes. This suggests that complement is an ancient and conserved system of immunity.
- Heat-labile nature: Complement proteins are sensitive to heat and can be inactivated by heating serum at 56°C for 30 minutes. This prevents complement from causing unwanted damage to the host cells and tissues.
- Synthesis by liver cells and other cell types: Complement proteins are mainly synthesized by liver cells, which secrete them into the bloodstream. However, some complement proteins can also be produced by other cell types, such as macrophages, monocytes, neutrophils, B cells, and epithelial cells. The synthesis of complement proteins can be increased when complement is activated and consumed during an immune response.
- Binding to antigen-antibody complex: Complement proteins do not bind directly to antigens or antibodies, but only to antigen-antibody complexes. This ensures that complement is activated only when there is a specific immune recognition of foreign invaders. The binding of complement to antigen-antibody complexes initiates a cascade of reactions that leads to the activation of different complement pathways.
- Contribution to acquired and innate immunity: Complement plays a role in both acquired and innate immunity. Acquired immunity refers to the specific and adaptive response of the immune system to a particular antigen, mediated by antibodies and T cells. Innate immunity refers to the general and nonspecific response of the immune system to any foreign substance, mediated by natural killer cells, phagocytes, and cytokines. Complement contributes to acquired immunity by enhancing the function of antibodies and facilitating their clearance from the circulation. Complement also contributes to innate immunity by directly killing pathogens, attracting inflammatory cells, and stimulating the release of immunoregulatory molecules.
These are some of the main properties of complement that make it an important part of the immune system. In the next section, we will discuss the main effects of complement activation on different targets.
The complement system has four main effects that contribute to the defense of the host against foreign invaders and the clearance of damaged cells and immune complexes. These effects are:
- Lysis of cells: The complement system can directly kill certain cells, such as bacteria, viruses, allografts, and tumor cells, by forming pores in their membranes. This process is mediated by the membrane attack complex (MAC), which is composed of complement proteins C5b, C6, C7, C8, and C9. The MAC disrupts the integrity of the cell membrane, leading to osmotic lysis and cell death.
- Generation of mediators: The complement system can also produce various mediators that modulate the immune response and inflammation. These mediators include anaphylatoxins (C3a, C4a, and C5a), which induce mast cell degranulation and release of histamine and other inflammatory cytokines; chemotactic factors (C5a and C3a), which attract neutrophils, monocytes, and eosinophils to the site of infection; and opsonins (C3b and C4b), which coat the surface of pathogens and enhance their phagocytosis by macrophages and neutrophils.
- Facilitation of opsonization: Opsonization is the process by which pathogens are coated with molecules that make them more recognizable and digestible by phagocytes. The complement system facilitates opsonization by attaching C3b and C4b to the surface of microbes, either directly or through antigen-antibody complexes. These molecules act as opsonins that bind to complement receptors on phagocytes, such as CR1, CR3, and CR4. This enhances the phagocytosis and destruction of the pathogens by the phagocytes.
- Immune clearance: Immune clearance is the removal of immune complexes from the circulation and their transport to the spleen and liver for disposal. Immune complexes are formed when antibodies bind to antigens, such as soluble proteins or microbial components. These complexes can activate the complement system and become coated with C3b. The C3b-coated complexes can then bind to erythrocytes via CR1 receptors and be carried to the spleen and liver. There, they are transferred to macrophages that express CR1 receptors and are degraded by lysosomal enzymes.
These are the main effects of the complement system that help protect the host from infection and injury. In addition to these effects, the complement system also interacts with other components of the immune system, such as natural killer cells, dendritic cells, B cells, and T cells, to modulate their functions and enhance the adaptive immune response.
Complement is a complex system of proteins that plays an important role in the immune response. It has various properties that make it a versatile and effective defense mechanism against pathogens and foreign cells. Complement can:
- Cause lysis of cells by forming pores in their membranes
- Generate mediators that activate and recruit immune cells, induce inflammation, and regulate immune responses
- Facilitate opsonization by coating bacteria with molecules that enhance their phagocytosis
- Cause immune clearance by removing immune complexes from the circulation and delivering them to the spleen and liver
Complement is also involved in the interaction between the innate and acquired immunity, as it can be activated by both antigen-antibody complexes and pathogen-associated molecular patterns. Complement can also modulate the adaptive immune response by influencing the activation and differentiation of B and T cells.
Complement is a vital component of the immune system that protects the host from infections and diseases. However, complement can also cause damage to the host tissues if it is activated inappropriately or excessively. Therefore, complement is regulated by various factors that prevent its overactivation and limit its effects to the target cells.
Complement is a fascinating topic that has many implications for immunology, pathology, and medicine. By understanding the properties and functions of complement, we can better appreciate its role in health and disease.
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