The root of both “mannose” and “mannitol” is manna, which the Bible records as the food supplied to the Israelites during their journey in the region of Sinai.
Manna is from Heaven, according to the Hebrew Bible and to Jesus in the New Testament.
The mannose receptor is a C-type lectin primarily present on the surface of macrophages, immature dendritic cells and liver sinusoidal endothelial cells, but is also expressed on the surface of skin cells such as human dermal fibroblasts and keratinocytes.
A C-type lectin (CLEC) is a type of carbohydrate-binding protein domain known as a lectin.
Proteins that contain C-type lectin domains have a diverse range of functions including cell-cell adhesion, immune response to pathogens and apoptosis.
The mannose receptor recognizes terminal mannose, N-acetylglucosamine and fucose residues on glycans attached to proteins found on the surface of some microorganisms, playing a role in both the innate and adaptive immune systems.
Additional functions include clearance of glycoproteins from the circulation, including sulfated glycoprotein hormones and glycoproteins released in response to pathological events.
The mannose receptor recycles continuously between the plasma membrane and endosomal compartments in a clathrin-dependent manner.
The mannose receptor recognizes the patterns of carbohydrates that decorate the surfaces and cell walls of infectious agents, which appear to play a key role in host defense and provides a link between innate and adaptive immunity.
Mannose–binding lectin (MBL) is a serum protein of hepatic (liver) origin belonging to a family of Ca2+-dependent collagenous lectins, most of which are components of the innate immune system.
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.
Mannose-binding lectin (MBL) is a key innate immunity pattern-recognition protein, activates the lectin complement pathway.
MBL has strong biologic plausibility as an innate immunity candidate protein that could protect against influenza-related sepsis with and without bacterial co-infection.
MBL binds to microbial surface glycosylation residues and targets influenza virus via direct neutralization, by recognition of influenza hemagglutinin surface proteins on infected cells, and can also ameliorate severity by defending against bacterial pathogens. Additionally, influenza virus uses a glycan-binding entry mechanism to invade host cells, and lectins such as MBL may interfere directly with the entry of the pathogen into the cell.
Another important function of MBL is that this molecule binds senescent and apoptotic cells and enhances engulfment of whole, intact apoptotic cells, as well as cell debris by phagocytes.
The complement system can be activated through three pathways: the classical pathway, the alternative pathway, and the lectin pathway. One way that the most-recently discovered lectin pathway is activated is through mannose-binding lectin protein.
MBL binds to carbohydrates (to be specific, D-mannose and L-fucose residues) found on the surfaces of many pathogens. For example, MBL has been shown to bind to:
- yeasts such as Candida albicans
- viruses such as HIV and influenza A
- many bacteria, including Salmonella and Streptococci
- parasites like Leishmania
MBL deficiency is a risk factor for the development of infection.
Human cohort studies have described associations between MBL deficiency and susceptibility to meningococcal meningitis, human immunodeficiency virus (HIV) infection, hepatitis C virus (HCV) infection and severe bacterial and fungal infections producing sepsis.
MBL deficiency has also been associated with increased frequencies of bacterial, viral and fungal infections in both children and adults, particularly following bone marrow transplantation.
Studies of human immune cells suggest that MBL deficiency may influence proinflammatory cytokine production in monocytes, peripheral blood mononuclear cells, and neutrophils as well as neutrophil superoxide production.
Dendritic cells (DCs) are antigen-presenting cells which are central to the induction of antigen-specific immune responses. To induce antigen-specific immune responses, DCs are required to recognize and process foreign material and present antigenic peptides, costimulatory molecules and cytokines to cells of the adaptive immune system: namely to T and B lymphocytes. Recognition of foreign antigens and subsequent delivery of costimulatory and cytokine signals are regulated by interactions between pathogen and pathogen recognition receptors (PRRs) which are expressed by DCs, or present as soluble plasma pattern recognition proteins, including MBL.
MBL-D individuals display unique functional characteristics, including higher production of proinflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α.
As a pro-inflammatory cytokine, IL-6 plays an important role in the immune response. IL-6 regulates the expression of acute-phase response proteins, affects DC maturation and survival and has been reported to play a role in T-cell differentiation. In the clinical setting, high IL-6 levels are associated with poor prognosis and poor outcome in sepsis and systemic inflammatory response syndrome. Increased IL-6 produced by MDCs in MBL-D individuals may have important clinical implications and suggests a mechanism by which MBL-D individuals may suffer from a reduced ability to respond to the pathogen.
Mannose-binding lectin deficiency is a condition that affects the immune system. People with this condition have low levels (deficiency) of an immune system protein called mannose-binding lectin in their blood.
A lack of functional MBL to bind pathogens and activate the complement cascade may have important consequences for the health of an individual. Indeed, MBL deficiency has been associated with a number of important infectious, inflammatory and autoimmune disease states in humans.
People with mannose-binding lectin deficiency can develop infections of the upper respiratory tract and other body systems. Individuals 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.
Infants and young children with mannose-binding lectin deficiency seem to be more susceptible to infections than affected adults, 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.
Mannose-binding lectin plays an important role in the body’s immune response by attaching to foreign invaders such as bacteria, viruses, or yeast and turning on (activating) the complement system.
The complement system is a group of immune system proteins that work together to destroy foreign invaders (pathogens), trigger inflammation, and remove debris from cells and tissues. Mannose-binding lectin can also stimulate special immune cells to engulf and break down the attached pathogen.
With decreased levels of mannose-binding lectin, the body does not recognize and fight foreign invaders efficiently. Consequently, infections can be more common in people with this condition.
Deficiencies have been associated with susceptibility to autoimmune and infectious diseases.
MBL facilitates phagocytosis of cellular debris and may, therefore, prevent autoimmunity.
Researchers believe that a number of factors, including other genetic and environmental factors, are involved in the development of mannose-binding lectin deficiency and susceptibility to infection.
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 host. MBL recognizes carbohydrate patterns, found on the surface of a large number of pathogenic micro-organisms, including bacteria, viruses, protozoa, and fungi. Binding of MBL to a micro-organism results in activation of the lectin pathway of the complement system.
MBL in the blood is complexed with (bound to) another protein, a serine protease called MASP (MBL-associated serine protease). In order to activate the complement system when MBL binds to its target (for example, mannose on the surface of a bacterium), the MASP protein functions to cleave the blood protein C4 into C4a and C4b. The C4b fragments can then bind to the surface of the bacterium, and initiate the formation of a C3-convertase. The subsequent complement cascade catalyzed by C3-convertase results in creating a membrane attack complex, which causes lysis of the pathogen as well as altered-self in the context of apoptotic and necrotic cells.
The complement pathway plays an essential role in the innate and adaptive immune response. MASP proteins, through the function of MBL, are activated when it complexes with the pathogen recognition molecules of the lectin pathway, the mannose-binding lectin and the ficolins (FCN2). MASP proteins are also involved with coagulation factors such as thrombin, fibrinogen, factor XIII, and thromboxane.
MASP proteins function in the lectin pathway of complement, which performs a key role in innate immunity by recognizing pathogens through patterns of sugar moieties and neutralizing them.
In order to activate the complement system when MBL binds to its target (for example, mannose on the surface of a bacterium), the MASP protein functions to cleave the blood protein C4 into C4a and C4b. The C4b fragments can then bind to the surface of the bacterium, and initiate the formation of a C3-convertase.
A mannose-binding lectin deficiency leads to a complement deficiency!
Complement deficiency is an immunodeficiency of absent or suboptimal functioning of one of the complement system proteins. Because there are redundancies in the immune system, many complement disorders are never diagnosed, some studies estimated that less than 10% are identified.
MBL has been reported as influencing Toll-like receptor 2 (TLR2) and TLR6 responses.
The mannose-binding lectin (MBL) pathway of the complement cascade has an essential role in the eradication of Borrelia burgdorferi (Lyme Disease). Deficiency in the MBL pathway of the complement cascade is a risk factor for developing disseminated Ab+ LB.
Malfunctions of MBL affects up to 50% of individuals in some populations.
More than two-thirds of patients with mycoplasma infections had genotypic MBL deficiency(compared with one-third in the general population).
In summary, up to 50% of individuals in some populations are affected by mannose-binding lectin deficiency. This leads to a complement deficiency to which only 10% are identified.
In other words, up to 90% of affected individuals have a propensity towards a malfunctioning immune system through MBL-D and complement deficiency!!!
Is it any wonder society is so plagued with infectious disease and malfunctioning immune systems?
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