Immune response Lectin Induced complement pathway
Lectin complement pathway The complement system is the major effector of the humoral branch of the immunesystem, acting to protect the host from microorganisms such as bacteria. Complement components are designated by numerals ( C1 - C9 ), by lettersymbols (e.g., Complement factor I ( Factor I )), or by trivial names. Peptidefragments formed by activation of a component are denoted by small letters , . In most cases, the smaller fragment resulting from cleavage of a component isdesignated 'a' and the larger fragment designated 'b' (e.g., Complement componentC3a, Complement component C3b; note that Complement C2 is anexception: Complement component C2a is the larger cleavage fragment) . The larger fragments bind to the target near the site of activation, and the smallerfragments diffuse from the site and can initiate localized inflammatory responses bybinding to specific receptors, such as Complement component receptor 1 ( CR1 ),Complement component receptor 2 ( CD21 ), complex of Integrin alpha M and Integrinbeta 2 ( alpha-M/beta-2 integrin ) and complex of Integrin alpha X and Integrinbeta 2 ( alpha-X/beta-2 integrin ) (the receptors for iC3b ), Complementcomponent 3a receptor 1 ( CR3aR ) and Complement component 5a receptor 1 (CR5aR ) , , . Complement fragments interact with one another to form functional complexes. Lectins such as Ficolin 3 ( H-Ficolin ), Ficolin 2 ( L-Ficolin ) andMannose-binding lectin 2 soluble ( MBL ) are proteins that recognize and bind tospecific carbohydrate targets . The lectin pathway, like the alternativepathway, does not depend on antibodies for its activation. The lectin pathway isactivated by the binding of MBL to mannose residues on glycoproteins orcarbohydrates on the surface of microorganisms , .MBL is an acute phase protein produced in inflammatory responses. Its function inthe complement pathway is similar to that of Complement component 1 q subcomponent (C1q ), which it resembles in structure . After MBL binds tothe surface of a cell or pathogen, Mannan-binding lectin serine peptidase 1 and 2 (MASP1 and MASP2 ), bind to MBL . The active complexformed by this association causes cleavage and activation of C4 and ComplementC2. The MASP1 and MASP2 proteins have structural similarity toComplement component 1 r subcomponent ( C1r ) and Complement component 1 ssubcomponent ( C1s ) and mimic their activities. C3 convertase (C2bC4b) andC5 convertase (C2aC4bC3b) are formed via assembly of Complement componentC4b, Complement component C2a and additional Complement component C3bmolecules without specific antibody binding. This mechanism represents an importantinnate defense mechanism comparable to the alternative complement pathway , , , . Smaller fragments resulting from complement cleavage, Complement component C3aand Complement component C5a, called anaphylatoxins, bind to receptorsCR3aR and CR5aR on the surface of mast cells and blood basophils. Thesecomplement components induce degranulation, with release of histamine and otherbiologically active mediators . Factor I is a major regulator of complement. As a protease it has veryrestricted specificity, cleaving only Complement component C3b or Complementcomponent C4b in the presence of a cofactor such as Complement factor H ( FactorH ). Cleavage of Complement component C3b by Factor I yieldsiC3b, a major opsonin . The classical, alternative, or lectin complement pathways lead to the production of anactive C5 convertase (C2aC4bC3b) . The terminal sequence ofcomplement activation involves Complement component C5b, C6, C7,C8, and C9, which interact sequentially to form a macromolecular structurecalled SC5b-9 membrane attack complex. This complex forms a large channel throughthe membrane of the target cell, enabling ions and small molecules to diffuse freelyacross the membrane . The latest step of complement activation is also controlled by the membrane-associatedcomplement regulatory protein CD59 that prevents the formation of the SC5b-9membrane attack complex at the terminal step of complement activation cascade , . Plasma complement regulatory protein Clusterin canalso interfere with formation of the SC5b-9 membrane attack complex pore .