Complement System PDF

## 8. The complement Dr. Antonio Muñiz Buenrostro ### The Complement System The complement system is a part of the immune system that helps to fight off infection. The complement system is activated by a variety of stimuli, including the presence of pathogens, antibodies, and other immune comple...

## 8. The complement Dr. Antonio Muñiz Buenrostro ### The Complement System The complement system is a part of the immune system that helps to fight off infection. The complement system is activated by a variety of stimuli, including the presence of pathogens, antibodies, and other immune complexes. When activated, the complement system sets off a cascade of events that lead to the destruction of pathogens, the recruitment of immune cells to the site of infection and the removal of immune complexes. ### The Complement Cascade The complement cascade begins with the activation of a complement protein, C1. This protein is activated when it binds to an antigen, such as a pathogen or an antibody. This binding event leads to the formation of the C1 complex, which includes C1q, C1r and C1s. Activated C1s then activates C4 to form C4b and C2, then activates C2 to form C2a and C2b. C4b and C2a together form the C3 convertase, which converts C3 into C3a and C3b. ### The C3 Convertase The C3 convertase is an important element of the complement cascade. It is responsible for the activation of C3, resulting in the generation of C3a and C3b. C3a is an anaphylatoxin, which means that it can attract immune cells to the site of infection and promote inflammation and release of histamine. C3b is an opsonin, which means that it can coat pathogens and make them more easily recognized and destroyed by phagocytes. ### The C5 Convertase The C5 convertase is another important element of the complement cascade, forming from C3b and C4b. It is responsible for the activation of C5, resulting in the generation of C5a and C5b. C5a is another anaphylatoxin, which means that it can attract immune cells to the site of infection and promote inflammation. C5b is the first component of the membrane attack complex (MAC). ### The Membrane Attack Complex (MAC) The MAC is a pore-forming complex that can insert itself into the membrane of target cells. Once the MAC is formed, it allows fluids to leak out of the target cell, causing cell lysis. There are two main pathways for the complement cascade: the classical pathway and the alternative pathway. #### Classical Pathway The classical pathway is activated by the binding of C1 to immune complexes. These complexes are usually formed by the interaction of an antibody with an antigen. This pathway is important for fighting off infections that are mediated by antibodies. #### Alternative Pathway The alternative pathway is activated by the spontaneous activation of C3. This pathway is important for fighting off infections that are not mediated by antibodies. #### Lecture Image The lecture image shows the different stages of the complement cascade along both the classical and alternative pathways. It shows the main components of the pathway, including C1, C2, C3, C4, C5 and the MAC. It also highlights the key enzymes involved in the pathway, as well as the different steps involved in the activation of the complement system. An explanation of the different components of the pathway is given in the lecture image. These include: - C1: This protein complex initiates the classical pathway. - C2: This protein is activated by C1s and forms part of the C3 convertase. - C3: This protein is the key target of the complement cascade. Its cleavage results in the generation of C3a, which is an anaphylatoxin, and C3b, which is an opsonin. - C4: This protein is activated by C1s and forms part of the C3 convertase. - C5: This protein is activated by the C5 convertase, generating C5a, which is an anaphylatoxin, and C5b, which is the first component of the MAC. - C3 convertase: This enzyme is responsible for the cleavage of C3. It forms in either the classical or alternative pathways. - C5 convertase: This enzyme is responsible for the cleavage of C5. It forms in either the classical or alternative pathways. - MAC: This complex is formed from C5b, C6, C7, C8, and C9. It is a pore-forming complex that can insert itself into the membrane of target cells. - Factor B: This protein forms part of the C3 convertase in the alternative pathway. - Factor D: A very important protein, factor D activates factor B in the activation cascade. - Factor H: This protein regulates the activity of the alternative pathway. - Properdin (P): This protein stabilizes the C3 convertase in the alternative pathway. - MCP: This protein is one of the many regulatory proteins that bind to C3b and inactivate it. - DAF: This protein prevents the formation of the C3 convertase. - C1 Inhibitor: This protein is an inhibitor of circulating, activated C1. - CR1: This protein is an inhibitor of circulating, activated C3 convertases. - MBL: This protein aids in the activation of the lectin pathway. ### Regulation of the Complement System The complement system is a highly regulated system. There are a variety of mechanisms in place to prevent the complement system from becoming overactive and causing damage to the host. These mechanisms include: - The production of complement inhibitors, which are proteins that can inhibit the activity of complement proteins. - The presence of cell surface molecules that can bind to complement proteins and prevent them from activating. - The removal of complement proteins from the circulation. ### Diseases of the Complement System Deficiencies in the complement system can lead to a number of diseases, such as: - Recurrent infections: Deficiencies in the complement system can make individuals more susceptible to infections. - Autoimmune diseases: The complement system plays a role in clearing immune complexes, and deficiencies in the complement system can lead to the accumulation of these complexes, which can trigger an autoimmune response. ### Summary of Complement System Function - The complement system is a critical component of innate immunity. - The cascade is activated via three pathways (classical, alternative, lectin). - The complement system mediates the destruction of pathogens, the recruitment of immune cells to the site of infection and the removal of immune complexes.