The lectin pathway or lectin complement pathway is a type of
cascade reaction in the
complement system
The complement system, also known as complement cascade, is a part of the immune system that enhances (complements) the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism, promote inflammation, and at ...
, similar in structure to the
classical complement pathway
The classical complement pathway is one of three pathways which activate the complement system, which is part of the immune system. The classical complement pathway is initiated by antigen-antibody complexes with the antibody isotypes IgG and ...
,
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
The classical complement pathway is one of three pathways which activate the complement system, which is part of the immune system. The classical complement pathway is initiated by antigen-antibody complexes with the antibody isotypes IgG and ...
, the
lectin pathway does not recognize an antibody bound to its target. The lectin pathway starts with
mannose-binding lectin (MBL) or
ficolin
Ficolins are pattern recognition receptors that bind to acetyl groups present in the carbohydrates of bacterial surfaces and mediate activation of the lectin pathway of the complement cascade.
Structure
Ficolins (Fi+Col+Lin) are a group of olig ...
binding to certain sugars.
In this pathway, mannose-binding lectin binds to
mannose
Mannose is a sugar monomer of the aldohexose series of carbohydrates. It is a C-2 epimer of glucose. Mannose is important in human metabolism, especially in the glycosylation of certain proteins. Several congenital disorders of glycosylation ...
,
glucose
Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, using ...
, 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'' is a genus of rod-shaped (bacillus) Gram-negative bacteria of the family Enterobacteriaceae. The two species of ''Salmonella'' are ''Salmonella enterica'' and ''Salmonella bongori''. ''S. enterica'' is the type species and is fur ...
'', ''
Listeria
''Listeria'' is a genus of bacteria that acts as an intracellular parasite in mammals. Until 1992, 17 species were known, each containing two subspecies. By 2020, 21 species had been identified. The genus is named in honour of the British pio ...
'', and ''
Neisseria
''Neisseria'' is a large genus of 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''.
''Neisseria'' species are Gram-negativ ...
'' strains. Fungal pathogens such as ''
Candida albicans
''Candida albicans'' is an opportunistic pathogenic yeast that is a common member of the human gut flora. It can also survive outside the human body. It is detected in the gastrointestinal tract and mouth in 40–60% of healthy adults. It is us ...
'' and ''
Cryptococcus neoformans
''Cryptococcus neoformans'' is an encapsulated yeast belonging to the class Tremellomycetes and an obligate aerobe that can live in both plants and animals. Its teleomorph is a filamentous fungus, formerly referred to ''Filobasidiella neoforman ...
'' as well as some viruses such as
HIV-1
The subtypes of HIV include two major types, HIV type 1 (HIV-1) and HIV type 2 (HIV-2). HIV-1 is related to viruses found in chimpanzees and gorillas living in western Africa, while HIV-2 viruses are related to viruses found in the sooty mangabey ...
and
Respiratory syncytial virus
Respiratory syncytial virus (RSV), also called human respiratory syncytial virus (hRSV) and human orthopneumovirus, is a common, contagious virus that causes infections of the respiratory tract. It is a negative-sense, single-stranded RNA virus. ...
(RSV) are bound by MBL.
Mannan-binding lectin, also called mannose-binding protein, is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
belonging to the
collectin Collectins (collagen-containing C-type lectins) are a part of the innate immune system. They form a family of collagenous Ca2+-dependent defense lectins, which are found in animals. Collectins are soluble pattern recognition receptors (PRRs). Their ...
family that is produced by the
liver
The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...
and can initiate the
complement cascade
The complement system, also known as complement cascade, is a part of the immune system that enhances (complements) the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism, promote inflammation, and ...
by binding to
pathogen
In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a germ ...
surfaces.
MBL
MBL forms oligomers of subunits, which are trimers (such that 6- and 18-subunit oligomers correspond to a dimer and a hexamer, respectively). Multimers of MBL form a complex with
MASP1 (Mannose-binding lectin-Associated Serine Protease),
MASP2 and
MASP3, that are
protease
A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalyzes (increases reaction rate or "speeds up") proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the ...
zymogen
In biochemistry, a zymogen (), also called a proenzyme (), is an inactive precursor of an enzyme. A zymogen requires a biochemical change (such as a hydrolysis reaction revealing the active site, or changing the configuration to reveal the activ ...
s. The MASPs are very similar to C1r and C1s molecules of the classical complement pathway, respectively. 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 and
C2 into C4a, C4b, C2a, and C2b. In f, 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). 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 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 tends to bind to bacterial cell membranes. If it is not then inactivated, it will combine with C2a to form the classical
C3 convertase (C4bC2a) on the surface of the pathogen, as opposed to the alternative C3 convertase (C3bBb) involved in the alternative pathway. C4a and C2b act as potent
cytokine
Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...
s, with C4a causing degranulation of mast cells and basophils and C2b acting to increase vascular permeability. Historically, the larger fragment of C2 was called C2a but some publications now refer to it as C2b in keeping with the convention of assigning 'b' to the larger fragment.
Clinical significance
Mannose-binding Lectin deficiency - These individuals are prone to recurrent infections, including infections of the upper respiratory tract and other body systems. People with this condition may also contract more serious infections such as pneumonia and meningitis. Depending on the type of infection, the symptoms caused by the infections vary in frequency and severity.
Although the clinical significance of MBL-Deficiency is debated.
Infants and young children with mannose-binding lectin deficiency seem to be more susceptible to infections, but adults can also develop recurrent infections. In addition, affected individuals undergoing chemotherapy or taking drugs that suppress the immune system are especially prone to infections.
[ ]
See also
*
Classical complement pathway
The classical complement pathway is one of three pathways which activate the complement system, which is part of the immune system. The classical complement pathway is initiated by antigen-antibody complexes with the antibody isotypes IgG and ...
*
Alternative complement pathway
The alternative pathway is a type of cascade reaction of the complement system and is a component of the innate immune system, a natural defense against infections.
The alternative pathway is one of three complement pathways that opsonize an ...
*
Mannan-binding lectin
Mannose-binding lectin (MBL), also called mannan-binding lectin or mannan-binding protein (MBP), is a lectin that is instrumental in innate immunity as an opsonin and via the lectin pathway.
Structure
MBL has an oligomeric structure (400-700 kDa) ...
References
External links
* https://ghr.nlm.nih.gov/condition/mannose-binding-lectin-deficiency#diagnosis
*
{{Use dmy dates, date=April 2017
Complement system