Beruflich Dokumente
Kultur Dokumente
18 July 2018
Chronic Periodontitis
Polymicrobial
Synergy and
Dysbiosis
2. Complement system
6. Anti-microbial peptides
Text book: Janeway’s Immunobiology (Kenneth Murphy, Paul Travers and Mark Walport, Garland Science)
3
Evolution of the Immune System
• No immunological memory
encounter with the pathogen for the second time doesnt lead to a faster respons
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Overview of Innate Immunity
• Consists of:
▪ Physical barriers (e.g. mucins, saliva, tears, cells)
▪ Chemical barriers (e.g. anti-microbial peptides, enzymes, pH)
▪ Complement proteins provide immediate protection against infection
• 2nd objective: Contain and kill pathogens that get into tissues
even if it gets in, you dont want it to get in the circulation which can lead to systemic
infection
• 3rd objective: Trigger the adaptive immune response
Try bring in B and T cells to try kill the pathogen
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Complement Proteins
this is the reasoin why the innate immune system can respond
so quickly, theses proteins are already in the circulation ready to
respond
Complement System
• Trigger inflammation
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Complement System
Lectin = a carbohydrate-
binding protein.
C3 convertase is an enzyme
which acts on inactive protiens
and activates it and initiate
complement fragments
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Complement System
Inflammatory
response
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Complement System
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Key cells of the innate immune system
Key Cells of the Innate Immune System
• Keratinocytes (specialised epithelial cells): these are the first cells that are going
to come in contact with the pathogen
▪ E.g. Oral cavity, skin, etc.
• Mucosal epithelial cells: the cells play a barrier function
▪ Orogastrointestinal tract, respiratory tract, urogenital tract
these are innate immune system
cells
• Neutrophils
• Macrophages
• Dendritic cells
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Keratinocytes and Mucosal Epithelial Cells
in chronic periodontitis, the cells release factors which break
down the tight junctions and can gain entry
• Form a physical barrier (e.g. via
tight junctions) to prevent
microbial entry
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Keratinocytes and Mucosal Epithelial Cells
there is a
breakdown of
the barrier
though which
the pathogens
can enter the
body, leading to
a robust
inflammatory
response. with a
certain level of
inflammation,
there is tissue
damage. if there
is chronic
inflammation,
there is chronic
in homeostasis, there is breakdown of
very little inflammation the tissue and
so ensure that bacteria chronic tissue
are kept out of the body destruction
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Macrophages
• Arise from blood monocytes that have migrated into the underlying tissue
In the bone marrow, macrophages go to the site of infection and they become a macrophage.
• Highly phagocytic
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Macrophages
cricual role in
gingival health
and plays a role
in the bacteria
that colonise the
root of the tooth
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Macrophages
• Highly phagocytic
• Release various cytokines (e.g. IL-1b, TNF, IL-6, and IL-12), and
chemokines (e.g. CXCL8, CCL2)
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Adaptive immune response is
activated by these DCs. DCs
Dendritic Cells present the antigen to adaptive
immune cells
• Arise from myeloid and lymphoid
progenitor cells
Christiane Nusslein-Volhard
(1995 Nobel Prize
in Physiology or Medicine)
Jules Hoffmann
(2011 Nobel Prize
in Physiology or Medicine) Lemaitre B et al., Cell (1996) 86: 973-873
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Pattern Recognition Receptors (PRRs)
• Alternative names:
▪ MAMP = Microbe Associated Molecular Pattern
▪ DAMP = Danger Associated Molecular Pattern
LPS
TLR4 recognises
gram negative
bacteria as it
recognises LPS
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Pattern Recognition Receptors (PRRs)
• Alternative names:
▪ MAMP = Microbe Associated Molecular Pattern
▪ DAMP = Danger Associated Molecular Pattern
• Main families:
▪ Toll-like receptors (TLRs)
▪ NOD-like receptors (NLRs)
▪ RIG-I-like receptors (RLRs)
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Toll-Like Receptors (TLRs)
remember
what
these
recognise
• Inflammasome = multi-protein
complex consisting of a NLR
(e.g. NLRP3), ASC (an adaptor
protein), and Caspase-1 (a
protease) It is made as an inactive
version, the pro-IL-1B
needs to be cleaved into
• Activated Caspase-1 cleaves IL-1B to be activated IL-1b
pro-IL-1b to generate mature A highly potent inflammatory cytokine.
IL-1b, which is then released
Koizumi Y, Cellular Microbiology (2012) 14:149-54 35
Signalling by Pattern Recognition Receptors
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Immunology Lecture Series
Lecture 12: Innate Immune Response in Periodontitis (9:00 am, 15 Aug 2018)
Lecture 13: Adaptive Immune Response in Periodontitis (12:00 pm, 17 Aug 2018)
Lecture 4: Immune Subversion by Bacterial Pathogens in Periodontitis (9:00 am, 10 Sep 2018)