8.2 Complement functions in immunity
2 min read•july 25, 2024
The complement system is a powerful ally in our immune defense. It coats pathogens, making them easier for immune cells to spot and destroy. This process, called , kicks off a chain reaction that ramps up our body's response to invaders.
But complement doesn't stop there. It can punch holes in some bad guys, causing them to burst. It also helps clean up immune complexes and dead cells, preventing potential harm. Plus, it acts as a bridge between different parts of our immune system, making everything work better together.
Complement System in Immunity
Complement in opsonization and phagocytosis
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- Opsonization process coats pathogens with complement proteins enhancing recognition ( and primary opsonins)
- Enhanced occurs when phagocytes recognize opsonized pathogens via (, , )
- Increased efficiency of pathogen clearance accelerates immune response
- Amplification of immune response recruits more phagocytes to infection site creating positive feedback loop
Complement-mediated cell lysis
- formation process begins when C5 convertase cleaves C5 into and initiating assembly
- Sequential binding of , , , and proteins forms transmembrane pore (10-16 nm diameter)
- Lysis mechanism disrupts cell membrane integrity causing osmotic imbalance leading to cell death
- Target cells include gram-negative bacteria, enveloped viruses, and parasites (malaria)
Complement for immune complex clearance
- C1q binds to antibody-antigen complexes activating classical pathway
- Enhanced solubilization and removal by phagocytes prevents tissue damage
- Apoptotic cell clearance initiated by C1q recognition of altered cell surface molecules
- (MBL) binds to apoptotic cells promoting opsonization
- Prevention of autoimmunity through rapid removal of potentially harmful cellular debris
- Maintenance of tissue homeostasis by efficient clearance of dead cells
Complement as immune system link
- Enhancement of B cell responses via complement receptors (/) lowers activation threshold
- T cell modulation through complement receptors regulates differentiation and function
- Antigen presentation improved by by antigen-presenting cells
- Cytokine production stimulated by C3a and C5a as (histamine release)
- Memory response augmentation involves complement in germinal center reactions
- Enhanced antibody production and affinity maturation strengthen adaptive immunity
Key Terms to Review (23)
Anaphylatoxins: Anaphylatoxins are small peptide fragments that are generated during the complement activation process, specifically from the cleavage of complement proteins C3 and C5. They play a crucial role in promoting inflammation and recruiting immune cells to sites of infection or injury, amplifying the immune response.
Autoimmunity prevention: Autoimmunity prevention refers to the mechanisms and strategies that the immune system employs to avoid mistakenly attacking the body's own cells and tissues. This is crucial for maintaining self-tolerance, which ensures that the immune system can distinguish between foreign pathogens and self-antigens. Effective autoimmunity prevention mechanisms are essential for overall health, as failures in these processes can lead to autoimmune diseases, where the immune system becomes harmful rather than protective.
C3b: c3b is a crucial component of the complement system, which plays a significant role in immune responses by enhancing the ability of antibodies and phagocytic cells to clear pathogens from an organism. It is formed when the complement protein C3 is cleaved during the activation of the complement pathway, leading to opsonization of pathogens, making them easier for immune cells to identify and eliminate. c3b also participates in the formation of the membrane attack complex, contributing to cell lysis.
C4b: c4b is a fragment of the complement protein C4, which plays a crucial role in the immune response by facilitating the opsonization of pathogens and enhancing inflammation. It is part of the classical complement pathway, generated when C4 is cleaved by the enzyme C1, leading to the activation of downstream components that help target and eliminate foreign invaders.
C5a: C5a is a potent anaphylatoxin and a key pro-inflammatory peptide generated during the complement activation process, specifically from the cleavage of the complement protein C5. It plays a significant role in immune response by attracting immune cells to sites of infection or injury and promoting inflammation, thus connecting it directly to the various functions of complement in immunity.
C5b: c5b is a complement component that plays a crucial role in the immune response, particularly in the formation of the membrane attack complex (MAC). It is generated when the complement protein C5 is cleaved by the C5 convertase, leading to the assembly of various complement proteins that help to lyse pathogens and facilitate inflammation. This action is essential for the opsonization of pathogens and enhances phagocytosis, making it a key player in the body’s defense mechanisms.
C6: C6 is a component of the complement system, a crucial part of the immune response that helps the body identify and eliminate pathogens. It plays an essential role in the formation of the membrane attack complex (MAC), which creates pores in the membranes of target cells, leading to their destruction. This action contributes to both innate and adaptive immunity, enhancing the overall defense against infections.
C7: C7, or complement component 7, is a protein that plays a crucial role in the complement system, which is part of the immune response. It acts as an intermediary in the formation of the membrane attack complex (MAC), helping to lyse pathogens such as bacteria and infected cells. Understanding C7's function is essential for grasping how the complement system contributes to innate immunity and enhances the ability of antibodies and phagocytic cells to clear pathogens from an organism.
C8: C8, also known as complement component 8, is a protein that plays a crucial role in the immune response, particularly in the complement system which helps to eliminate pathogens. It is involved in forming the membrane attack complex (MAC) that punctures the membranes of target cells, contributing to cell lysis and promoting inflammation and opsonization. Understanding C8 is essential for comprehending how the immune system targets and destroys invaders like bacteria and viruses.
C9: C9, or complement component 9, is a crucial protein in the complement system, which is a part of the immune response that enhances the ability of antibodies and phagocytic cells to clear pathogens. This component plays a vital role in the formation of the membrane attack complex (MAC), which disrupts the integrity of bacterial cell membranes, leading to cell lysis. The action of C9 is essential for effective immune defense against infections, particularly by Gram-negative bacteria.
CD21: CD21, also known as complement receptor 2 (CR2), is a protein expressed on the surface of B cells and follicular dendritic cells that plays a vital role in the immune response by binding to complement components and facilitating B cell activation and differentiation. It acts as a bridge between the adaptive and innate immune systems, enhancing the ability of B cells to respond to antigens that are opsonized with complement proteins.
CD35: CD35, also known as complement receptor 1 (CR1), is a protein found on the surface of various immune cells that plays a vital role in the immune response by facilitating the clearance of immune complexes and pathogens. It acts by binding to complement proteins, specifically C3b and C4b, enhancing phagocytosis and promoting opsonization, which is essential for effective immunity.
Complement receptors: Complement receptors are specialized proteins found on the surface of immune cells that bind to complement proteins, facilitating various immune responses. These receptors play a crucial role in linking the complement system to cellular activities, enhancing the ability of immune cells to recognize and eliminate pathogens effectively. By interacting with complement components, these receptors help modulate inflammation and activate immune responses, connecting them to complement activation pathways and overall immune functions.
Complement-mediated uptake: Complement-mediated uptake refers to the process by which immune cells recognize and engulf pathogens or apoptotic cells that have been tagged by complement proteins. This tagging enhances the ability of immune cells, such as macrophages and neutrophils, to identify and eliminate these targets effectively. The complement system plays a crucial role in the immune response, facilitating both opsonization and the enhancement of phagocytosis.
CR1: CR1, or complement receptor 1, is a membrane-bound protein that plays a significant role in the immune system by binding to complement component C3b and aiding in the clearance of immune complexes and pathogens. This receptor is primarily expressed on the surface of immune cells like macrophages and B cells, enhancing their ability to recognize and eliminate opsonized targets through phagocytosis. The functionality of CR1 is vital for maintaining immune homeostasis and preventing excessive inflammation.
CR3: CR3, or complement receptor 3, is a type of protein found on the surface of immune cells that plays a key role in the immune response by recognizing and binding to complement-coated pathogens. This receptor is particularly important for phagocytosis, the process by which immune cells engulf and destroy foreign invaders, including bacteria and dead cells. By interacting with the complement system, CR3 enhances the ability of immune cells to identify and eliminate threats in the body.
Cr4: cr4 is a complement receptor that plays a crucial role in the immune system, specifically in the recognition and clearance of pathogens. It is primarily found on macrophages and neutrophils, helping these immune cells bind to complement-coated pathogens, enhancing phagocytosis and facilitating the immune response. This receptor is vital for mediating various immunological functions, including opsonization and cell signaling.
Immune complex clearance: Immune complex clearance refers to the process by which the immune system removes immune complexes, which are formed when antibodies bind to antigens. This mechanism is crucial for maintaining homeostasis and preventing tissue damage, as the accumulation of these complexes can lead to inflammation and autoimmune diseases. The complement system plays a vital role in this process, facilitating the recognition, opsonization, and subsequent removal of immune complexes by phagocytic cells.
Lytic mechanism: The lytic mechanism refers to a process by which certain immune components, particularly the complement system, cause the destruction of pathogens, such as bacteria and viruses, through the formation of pores in their membranes. This leads to cell lysis, or the breaking apart of the pathogen, ultimately resulting in its death. This mechanism is essential in the immune response, helping to eliminate infectious agents from the body.
Mac: MAC, or Membrane Attack Complex, is a crucial component of the immune system's complement pathway that forms pores in the membranes of target cells, leading to cell lysis and death. By integrating the immune response, MAC plays a significant role in protecting the body against pathogens, particularly bacteria. Its formation is a key event in the complement cascade, illustrating how the immune system can directly destroy invaders.
Mannose-binding lectin: Mannose-binding lectin (MBL) is a protein that plays a crucial role in the innate immune system by recognizing and binding to specific sugar patterns found on the surface of pathogens. This binding activates the complement system, enhancing opsonization and promoting phagocytosis, which is essential for clearing infections.
Opsonization: Opsonization is the process by which pathogens are marked for destruction by immune cells, making them more recognizable to phagocytes. This enhances the efficiency of the immune response by promoting the binding of these pathogens to immune cells, facilitating their ingestion and elimination. Opsonization connects to various immune mechanisms, including innate immunity, antibody function, antigen-antibody interactions, and complement activation pathways.
Phagocytosis: Phagocytosis is the process by which certain cells, known as phagocytes, engulf and digest foreign particles, pathogens, or cellular debris. This crucial mechanism is a key component of the innate immune response, aiding in the clearance of infections and the maintenance of tissue homeostasis. Phagocytosis connects to various aspects of immune function, including the role of immune cells in recognizing threats, the activation of signaling pathways, and interactions with other immune components, such as the complement system.