The Mannan-binding lectin pathway (also known simply as the Lectin Pathway) is similar in structure to the classical complement pathway

Classical complement pathway

The Classical pathway of activation of the complement system is a group of blood proteins that mediate the specific antibody response. The main activators of the Classical Pathway are antigen-antibody complexes.-Initiation:...

, in that, after activation, it proceeds through the action of C4 and C2 to produce activated complement proteins further down the cascade. In contrast to the classical complement pathway

Classical complement pathway

The Classical pathway of activation of the complement system is a group of blood proteins that mediate the specific antibody response. The main activators of the Classical Pathway are antigen-antibody complexes.-Initiation:...

, it is not antibody-dependent.

In this pathway, mannose-binding lectin binds to mannose

Mannose

Mannose is a sugar monomer of the aldohexose series of carbohydrates. Mannose is a C-2 epimer of glucose. It is not part of human metabolism, but is a component of microbial cell walls, and is therefore a target of the immune system and also of antibiotics....

, glucose

Glucose

Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...

 or other sugars with 3- and 4-OH groups placed in the equatorial plane, in terminal positions on carbohydrate or glycoprotein components of microorganisms including bacteria such as Salmonella

Salmonella

Salmonella is a genus of rod-shaped, Gram-negative, non-spore-forming, predominantly motile enterobacteria with diameters around 0.7 to 1.5 µm, lengths from 2 to 5 µm, and flagella which grade in all directions . They are chemoorganotrophs, obtaining their energy from oxidation and reduction...

, Listeria, and Neisseria

Neisseria

The Neisseria is a large genus of commensal bacteria that colonize the mucosal surfaces of many animals. Of the 11 species that colonize humans, only two are pathogens. N. meningitidis and N. gonorrhoeae often cause asymptomatic infections, a commensal-like behavior...

strains. Fungal pathogens such as Candida albicans

Candida albicans

Candida albicans is a diploid fungus that grows both as yeast and filamentous cells and a causal agent of opportunistic oral and genital infections in humans. Systemic fungal infections including those by C...

and Cryptococcus neoformans

Cryptococcus neoformans

Cryptococcus neoformans is an encapsulated yeast that can live in both plants and animals. Its teleomorph is Filobasidiella neoformans, a filamentous fungus belonging to the class Tremellomycetes. It is often found in pigeon excrement....

as well as some viruses such as HIV-1 and Respiratory syncytial virus (RSV) are bound by MBL.

Mannan-binding lectin

Mannan-binding lectin

Mannose-binding lectin , also named mannose- or mannan-binding protein , is an important factor in innate immunity.-Function:MBL belongs to the class of collectins in the C-type lectin superfamily, whose function appears to be pattern recognition in the first line of defense in the pre-immune...

 (MBL, also called mannose-binding lectin) is a protein

Protein

Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

 belonging to the collectin

Collectin

Collectins are soluble pattern recognition receptors belonging to the superfamily of collagen containing C-type lectins.Eight collectins have been identified including mannan-binding lectin , surfactant protein A , surfactant protein D , collectin liver 1 , collectin placenta 1 , conglutinin,...

 family that is produced by the liver

Liver

The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...

 and can initiate the complement cascade by binding to pathogen

Pathogen

A pathogen gignomai "I give birth to") or infectious agent — colloquially, a germ — is a microbe or microorganism such as a virus, bacterium, prion, or fungus that causes disease in its animal or plant host...

 surfaces.

MBL

MBL is a 6- to 18-headed molecule that forms a complex with MASP-1 (Mannan-binding lectin-Associated Serine Protease), MASP-2 and MASP-3, two protease

Protease

A protease is any enzyme that conducts proteolysis, that is, begins protein catabolism by hydrolysis of the peptide bonds that link amino acids together in the polypeptide chain forming the protein....

 zymogen

Zymogen

A zymogen is an inactive enzyme precursor. A zymogen requires a biochemical change for it to become an active enzyme. The biochemical change usually occurs in a lysosome where a specific part of the precursor enzyme is cleaved in order to activate it...

s. The MASPs are very similar to C1r and C1s molecules of the classical complement pathway, respectively, and are thought to have a common evolutionary ancestor. When the carbohydrate-recognising heads of MBL bind to specifically arranged mannose residues on the surface of a pathogen, MASP-1 and MASP-2 are activated to cleave complement components C4

Complement component 4

Complement component 4 is a protein involved in the complement system.It is cleaved into proteins 4a and 4b.* C4a is an anaphylatoxin.* C4b forms part of C3-convertase, in conjunction with 2a:* C4b can bind CR1....

 and C2

Complement component 2

Complement C2 is a protein that in humans is encoded by the C2 gene. The protein encoded by this gene is part of the classical pathway of complement system.-Further reading:...

 into C4a, C4b, C2a, and C2b. In addition, two smaller MBL-associated proteins (MAps) are found in complex with MBL. MBL-associated protein of 19 kDa (MAp19) and MBL-associated protein of 44 kDa (Map44

Map44

Mannose-binding lectin-associated protein of 44 kDa is a protein arising from the human MASP1 gene. MASP-1, MASP-3 and MAp44 are alternative splice products of the MASP1 gene. MAp44 has been suggested to act as a competitive inhibitor of lectin pathway activation, by displacing MASP-2 from MBL,...

). MASP-1, MASP-3 and MAp44 are alternative splice products of the MASP1 gene, while MASP-2 and MAp19 are alternative splice products of the MASP-2 gene. MAp44

Map44

Mannose-binding lectin-associated protein of 44 kDa is a protein arising from the human MASP1 gene. MASP-1, MASP-3 and MAp44 are alternative splice products of the MASP1 gene. MAp44 has been suggested to act as a competitive inhibitor of lectin pathway activation, by displacing MASP-2 from MBL,...

 has been suggested to act as a competitive inhibitor of lectin pathway activation, by displacing MASP-2 from MBL, hence preventing cleavage of C4 and C2

C3 convertase

C4b and C2a combine on the surface of the pathogen to form C3 convertase (C4b and C2a), while C4a and C2a act as chemoattractants.

C3 convertase is, in classical terms, C4b2a.

Clinical significance

It has been found that people deficient in MBL experience a substantial increase in infections during the early years of childhood.

External links

• http://pathmicro.med.sc.edu/ghaffar/complement.htm