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Innate Immunity
Innate Immunity
Epithelial barriers
Soluble molecules
Pattern-recognition receptors:
TLRs, NLRs, scavenger Rs,
C-type lectin Rs
Macrophages
Neutrophils
Mannose-Binding Lectin (MBL)
• Circulating in blood C-type lectin, contains multiple CRDs
(carbohydrate recognition domain);
• Member of collectin family of proteins, which contain both
collagen-like and lectin (sugar-binding) domains. Other
members of the family: surfactant proteins A and D in lung;
• Binds to glycans displayed on the surfaces of
microorganisms (particular orientation of certain sugar
residues and their spacing are important);
• Can initiate the lectin pathway of complement activation;
• Once formed, the MBL-pathogen complex is bound by
phagocytes;
• Recognizes cryptic self-antigens, that are exposed by celldeath or reperfusion injury, or are modified by disease states.
Control of MBL Production
Further Reading: Teillet et al. The Journal of Immunology, 2005, 174: 2870-2877
MBL Structure and Its Selective Binding to
Carbohydrates
MBL Interactions with Microorganisms
MBL Interactions with Altered Self
• MBL binds to apoptotic and necrotic cells.
• Binds to stressed or damaged cells (after
ischemia reperfusion injury).
• Binds to some transformed human tumor cell
lines, that have abberant glycosylation patterns
(colon adenocarcinoma, colorectal carcinoma).
• Binds galactose isoforms on antibodies in
rheumatoid joints, polymeric IgA, and certain
glycoforms of IgM.
MBL and Complement Activation
MBL and Phagocytosis
Phagocytosis without opsonization
Opsonin-mediated Phagocytosis
Other Receptors for Inflammatory
Signaling
MBL and Phagosome-dependent
TLR Signaling
Physiological Role of MBL
• Early effect in mammals during lag period, that is
required to develop an antibody response against
infectious agents.
• MBL alone can account for susceptibility to infection.
• There’s no evolutionary advantage, nor disadvantage to
different MBL alleles.
• MBL can act as a disease modifier in the context of other
defects in innate immunity.
• Key role in containing and preventing the systemic
spread of the bacterial infection.
• MBL contributes to the pool of genes that together
comprise to the “innate immune haplotype”, that
ultimately defines the immunological fitness of the host.
Summary
• MBL is a pattern-recognition molecule that contains CRD
for glycan interaction and is capable of activating
complement via lectin pathway.
• MBL is able to recognize carbohydrate structures from
both infectious agents and altered self.
• MBL mediates defense against microbes via
phagocytosis or extracellular complement mediated
effector functions.
• MBL acts as a TLR2/6 co-receptor within the cell in
directing intracellular signaling.
• Molecules such as MBL coordinate internalization, ligand
delivery and ligation of pattern recognition receptors,
which ultimately define the response of the phagocytic
cell to the ingested organism.