Download Complement receptors

Manifestation of Novel Social Challenges of the
European Union
in the Teaching Material of
Medical Biotechnology Master’s Programmes
at the University of Pécs and at the University
of Debrecen
Identification number: TÁMOP-4.1.2-08/1/A-2009-0011
Manifestation of Novel Social Challenges of the
European Union
in the Teaching Material of
Medical Biotechnology Master’s Programmes
at the University of Pécs and at the University
of Debrecen
Identification number: TÁMOP-4.1.2-08/1/A-2009-0011
Tímea Berki and Ferenc Boldizsár
Signal transduction
COMPLEMENT
RECEPTORS
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Basic functions of the
complement
• Opsonization: enhancing phagocytosis
of antigens
• Chemotaxis: attracting macrophages and
neutrophils
• Lysis: rupturing membranes of foreign
cells
• Clumping of antigen-bearing agents
• Altering the molecular structure of
viruses
• Transport of immuncomplexes by RBCs
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Opsonins
•
•
Acute phase proteins like mannosebinding lectin (MBL), C-reactive
protein (CRP)
C3b, C4b complement factors
•
Surfactant proteins in the alveoli
SP-A and SP-D
•
The antibody molecule IgG can
function as an opsonin
Secreted Pattern
Recognition Receptors
(PRRs)
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• Complement receptors, collectins
• Pentraxin proteins such as serum amyloid and
C-reactive protein
• Lipid transferases
• Peptidoglycan recognition proteins (PGRs)
and the LRR, XA21D are all secreted proteins
• One very important collectin is mannanbinding lectin (MBL), a major PRR of the
innate immune system that binds to a wide
range of bacteria, viruses, fungi and
protozoa. MBL predominantly recognizes
certain sugar groups on the surface of
microorganisms but also binds phospholipids,
Role of complement
receptors
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• Complement receptors are responsible for
detecting pathogens by mechanisms not
mediated by antibodies
• Complement activity is not antigen
sensitive, but can be triggered by specific
antigens
• Therefore complement (a group of proteins
in the serum that help achieve phagocytosis
and lysis of antigens) is also part of the
innate humoral immune system
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Complement receptors
CR #
Name
Cluster of
differentiation (CD)
CR1
-
CD35
CR2
-
CD21
CR3
Macrophage-1 antigen or „integrin alphaMbeta2”
CD11b+CD18
CR4
Integrin alphaXbeta2 or „p150,95”
CD11c+CD18
-
C3a receptor
-
-
C5a receptor
CD88
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Complement receptors
APC
T cell
CR1
Antigen recognition
and uptake
CR1
Inhibits cell proliferation
Expressed on <15%
CR2
CR3
CR2
CR3
CR4
Unknown
Expressed on <5%
CR4
Pathogen recognition
and/or clearance
Modulation of TH1/TH2
commitment
Antigen recognition
and uptake
Cytokine modulation
and APC maturation
CRIg
SIGNR1
C3aR
Cytokine modulation
Expressed on activation
C5aR
C5aR
T-cell trafficking
Upregulated by activation
C1qR
C1qRP
CD46
CD46
C3aR
CD55
CD55
CD59
CD59
Cytokine modulation
Activation/proliferation,
cytokine modulation and
lineage commitment
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CR1
Erythrocyte complement receptor 1 (CR1,
CD35):
• Also known as C3b/C4b receptor and immune
adherence receptor
• It is found on erythrocytes, leukocytes,
glomerular podocytes, and splenic follicular
dendritic cells
• The Knops blood group system is a system of
antigens located on this protein. The
protein mediates cellular binding to
particles and immune complexes that have
activated complement
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Role of CR1
• CR1 serves as the main system for processing
and clearance of complement opsonized immune
complexes
• It has been shown that CR1 can act as a
negative regulator of the complement
cascade,
• It mediates immune adherence and
phagocytosis and inhibits both the classic
and alternative pathways
• The number of CR1 molecules decreases with
aging of erythrocytes (100-1000/cell) in
normal individuals and is also decreased in
pathological conditions such as SLE, HIV
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CR2
Complement component receptor 2 (CR2, CD21):
• Also known as, 3d /Epstein Barr virus receptor
• CR2 on mature B cells form a complex with two other
membrane proteins, CD19 and CD81(=TAPA-1). The CR2CD19-CD81 complex is often called the B cell coreceptor complex, because CR2 binds to antigens
through attached C3d (or iC3b or C3dg) when the
membrane IgM binds to the antigen. This results in
the B cell having greatly enhanced response to the
antigen.
• Complement receptor 2 has been shown to interact with
CD19.
• Epstein Barr Virus (EBV) binds to B cells at CR2
during infection of these cells. Yefenof et al.
(1976) found complete overlapping of EBV receptors
and C3 receptors on human B cells.
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C5aR
C5a receptor : also known as complement
component 5a receptor 1 (C5AR1) or CD88
is a G protein-coupled receptor for C5a
Overview of complement
receptor (CR) and Toll-like
receptor signaling
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Bacteria
Viruses
C3b
C5
iC3b
C1q
C5a
CR3
TLR
PI3K
Erk1/2
IRF-1,
IRF-8
Nucleus
C5aR
gC1qR
CD46
TLR4-induced IL-12 inhibited
by posttranscriptional mechanism
IL-12p35
IL-12/IL-23p40
IL-23p19
IL-27p28
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Toll-like receptors-pattern
recognition
Peptidoglycan (G+)
Lipoprotein
Lipoarabinomannan (Mycobacteria)
LPS (Leptospira)
LPS (Porphyromonas)
GPI (Trypanosoma cruzi)
Yymosan (Yeast)
dsRNA
TLR1
TLR2
TLR2
TLR6
Lipoteichoic acids (G+)
RVS F protein
Unmethylated
LPS (G-)
Flagellin CpG DNA
TLR3
CD14
MD-2 TLR4
TLR5
TLR9
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Toll-like receptors (TLRs)
• They are single, membrane-spanning, noncatalytic receptors that recognize
structurally conserved molecules derived
from microbes
• They receive their name from their
similarity to the protein coded by the Toll
gene identified in Drosophila in 1985 by
Christiane Nüsslein-Volhard. The gene in
question, when mutated, makes the Drosophila
flies look unusual, or 'weird'. The
researchers were so surprised that they
spontaneously shouted out in German "Das ist
ja toll!" which translates as "That´s wild!"
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TLR types
LPS
LBP
TLR2
TLR4
MD2
CD14
dsRNA
MyD88
MyD88
TLR9
TLR7
TLR3
RIG-1
JAK2
MDA-5
IPS1
PI3K
IKKe
mTOR
MyD88
PKA
TRIF
TAK1
MKKs
PKR
p50
lkB
p65
p38
JNK
TBK1