41. Immune Reactions Employing the Complementary System

Immune Reactions Employing the Complementary System

• Introduction and Overview
• The complement system is a series of proteins that work with antibodies to enhance the immune response.
• It is a primary effector system for both innate and adaptive immunity.
• It is a group of plasma proteins (complement proteins C1-C9) present in plasma as inactive forms.
• These proteins are activated by microbes and promote inflammation and destruction of the microbes.
• The complement system is a biochemical cascade of proteins in the bloodstream.
• It is a non-specific defence system against pathogens, but can also be directed toward specific targets by antibodies.
• It is a big part of the humoral immune system. Humoral immunity is mediated by macromolecules in extracellular fluids (humours), including complement proteins.
• The complement system is an important humoral factor in nonspecific immune defences.
• Activation Pathways
• The complement system is activated through three main pathway :
• CLASSICAL, ALTERNATIVE, AND LECTIN
• All three pathways converge by acting on the key complement protein C3, thus activating it.
• Details of Activation Pathways
• The Classical pathway is initiated when antibodies (IgG or IgM) bind to an antigen on the surface of a pathogen.
• The C1 complex binds to the antigen-antibody complex. This leads to the activation of C4, C2, and other complement proteins, forming C3 convertase.
• Pentameric IgM represents a particularly efficient C activator.
• It is a component of acquired immunity and is involved in adaptive immunity as it depends on antibodies.
• The Alternative pathway can be activated by the surface of pathogens, such as bacteria, fungi, or viruses, without needing antibodies.
• It is activated directly via the action of products derived from microorganisms, endotoxins, polysaccharides, or aggregated IgA.
• It is a component of innate immunity.
• This pathway involves factors B and D. C3b produced in this pathway acts as C3 convertase.
• The Lectin pathway uses mannose-binding ligand (MBL- plasma protein) that binds to mannose on microbes.
• It is a component of innate immunity.
• Key Steps in Complement Activation
• All three pathways converge by acting on the key complement protein C3, thus activating it.
• All three pathways activate protease C3-convertase, cleaving C3 into C3a and C3b.
• C3b in turn activates factors B and D (Alternative pathway).
• In the Classical pathway, C4b2a forms the C3 convertase. C3b can also enhance the alternative C3 convertase (C3bBb).
• Both pathways lead to the formation of C5 convertase (C4b2a3b or C3bBb3b).
• C5 convertase splits C5 into C5a and C5b.
• Major Functions and Outcomes