Answer to Question #256714 in Microbiology for Ene

Question #256714
Explain thoroughly, the complement system under the following headlines: 1. Types 2. Activation 3. Complement fixation test
Expert's answer

the complement system is part of the immune system that enhances the ability of antibodies and phagocytic cells to combat pathogens and induce a series of inflammatory responses that help to fight infection. A large number of complement proteins are proteases that are activated by proteolytic cleavage.

  • Types of the complement system- 1) Classical Pathway. 2) Lectin Pathway and 3) Alternative Pathway
  • Activation- 1) Classical Pathway- is triggered by activation of the C1-complex. The C1 complex is made up of 1 molecule of C1q, 2 molecules of C1r and 2 molecules of C1s. This happens when C1q binds with immunoglobulin M(IgM) or IgG that is complexed with the antigens. A single Pentametric immunoglobulin is enough to activate this pathway, whereas IgG needs to be at least 6 in number for pathway activation. Or the C1q can directly bind to the pathogen for activation. This leads to conformational changes in the C1q molecule, which leads to the activation of two C1r molecules. and then they cleave C1s. 2) Lectin Pathway- is activated by binding of Mannose-binding lectin(MBL) to mannose residues on the pathogen surface, which then activates or stimulates the MBL-associated serine proteases, MASP-1, and MASP-2. This then splits C4 into C4a and C4b and C2 into C2a and C2b. Later the C4b and C2b bind together to form the classical C3-convertase. This causes the activation of the lectin pathway to kill antigens. 3) Alternative Pathway- This pathway is continuously activated at a low rate due to the unprompted C3 hydrolysis caused due to the breakdown of the internal thioester bonds. C3b is generated from C3 by a C3 convertase enzyme complex but in the fluid phase, this C3b can be inactivated by factor H and Factor I. But when the internal thioester of C3 reacts with a hydroxyl or amino group of a molecule on the surface of antigen or a pathogen. The C3b that is now covalently bound to the surface is protected from factor H-mediated inactivation. The surface-bound C3b now binds factor B to form C3bB and this complex in the presence of factor D will be cleaved into Ba and Bb. Thereby, the Bb will remain associated with C3b to form C3bBb, which is the alternative pathway C3 convertase.

  • Complement fixation test- this is an immunological test used to detect the presence of either specific antigen or specific antibody in the blood serum based on the complement fixation occurrence. Very useful to diagnose infectious diseases, particularly with microbes that are not easily detected by culture methods. It is also used in rheumatic diseases. though the test is used to detect the antibodies in serum, it can also be used to identify the antigens.

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