Download MUKOSA-SISTEM-IMMUN-BAKTERI-VIRUS-CACING

The Mucosal
Immune System
• The organization of the
mucosal immune system
• The mucosal response to
infections and regulation of
mucosal immune
responses
Musketeers Course October 2008
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The mucosal response to infection and regulation of mucosal immune responses
Musketeers Course October 2008
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The mucosal response to infection and regulation of mucosal immune responses
Many enteric pathogens need to exploit host
mechanisms as part of their invasive strategies
Musketeers Course October 2008
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The mucosal response to infection and regulation of mucosal immune responses
Shigella flexneri infects intestinal epithelial cells triggering
activation of the NFkB pathway
Musketeers Course October 2008
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The mucosal response to infection and regulation of mucosal immune responses
NOD: nucleotide binding oligomerization domain
Musketeers Course October 2008
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The mucosal response to infection and regulation of mucosal immune responses
Intestinal pathogens
Bacteria
Viruses
Parasites
induce inflammation
Musketeers Course October 2008
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The mucosal response to infection and regulation of mucosal immune responses
Mucosal Tolerance
Entry of nonpathogenic antigens
e.g. food proteins
Musketeers Course October 2008
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The mucosal response to infection and regulation of mucosal immune responses
The concept of mucosal tolerance.
Prolonged mucosally administered
antigens induce both systemic and
mucosal unresponsiveness
to the same Ag when challenged in
the presence of adjuvant.
2 weeks later
Musketeers Course October 2008
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The mucosal response to infection and regulation of mucosal immune responses
Proposed dosedependent
mechanisms of
oral tolerance.
Musketeers Course October 2008
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The mucosal response to infection and regulation of mucosal immune responses
The healthy intestine contains large quantities of bacteria but does
not generate productive immunity against them
Metabolism of dietary
constituents
Degrading toxins
Produce vitamin K & short
chain fatty acids
Maintaining epithelium
Compete the pathogens
Inhibit pro-inflammatory
signals
Musketeers Course October 2008
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The mucosal response to infection and regulation of mucosal immune responses
Clostridium difficile infection after treatment by antibiotics
Musketeers Course October 2008
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The mucosal response to infection and regulation of mucosal immune responses
Mucosal DC regulate
the induction of
tolerance and
immunity
Musketeers Course October 2008
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The mucosal response to infection and regulation of mucosal immune responses
Commensal bacteria can prevent inflammatory responses
in the intestine
Musketeers Course October 2008
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The mucosal response to infection and regulation of mucosal immune responses
Commensal bacteria
 recognize by epithelial
cells
EC secretion of cytokines
inhibit the expression of
pro-inflammatory cytokines
by DC and macrophage
 DC & macrophages
secrete signals for the
expansion and/or survival
of T cells with regulatory
capacities, including
regulatory T cells, T
regulatory type 1 (TR1)
cells, T helper 2 (TH2) cells
and TH3 cells.
Musketeers Course October 2008
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The mucosal response to infection and regulation of mucosal immune responses
The mucosal immune system must maintain a balance between protective
immunity and mucosal tolerance to a large number of different antigens
Musketeers Course October 2008
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The mucosal response to infection and regulation of mucosal immune responses
Celiac disease a breakdown of
oral tolerance
Musketeers Course October 2008
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The mucosal response to infection and regulation of mucosal immune responses
Parasites
Most helminths can
induce both
protective (Th2)
and pathological
(Th1) immune
responses
Musketeers Course October 2008
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The mucosal response to infection and regulation of mucosal immune responses
Giardia lamblia
•
•
Production of antibodies
Infiltration of mucosa by
effector cells
Musketeers Course October 2008
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The mucosal response to infection and regulation of mucosal immune responses
Cryptosporidium parvum & T. gondii
•
•
Intracellular pathogens
Require CD4Th1 and CD8 T cells to clear them
Musketeers Course October 2008
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The mucosal response to infection and regulation of mucosal immune responses
Chronic infections of intestinal helminths
• Production of mediators that
dampen the innate immune
responses
• Expression of decoy receptors of
cytokines and chemokines
• Downregulation of IL-12 by DC
 encourage generation of IL-10
producing Treg
Musketeers Course October 2008
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The mucosal response to infection and regulation of mucosal immune responses
Protective and pathological responses to intestinal helminths
Musketeers Course October 2008
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The mucosal response to infection and regulation of mucosal immune responses
Musketeers Course October 2008
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