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Musketeers Course October 2008 1 The Mucosal Immune System The organization of The organization of the mucosal immune the mucosal immune system system The mucosal response The mucosal response to infections and to infections and regulation of regulation of mucosal immune mucosal immune responses responses
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Musketeers Course October 20081 The Mucosal Immune System The organization of the mucosal immune systemThe organization of the mucosal immune system The.

Jan 16, 2016

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Page 1: Musketeers Course October 20081 The Mucosal Immune System The organization of the mucosal immune systemThe organization of the mucosal immune system The.

Musketeers Course October 2008

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The Mucosal Immune System

The Mucosal Immune System

• The organization of the The organization of the mucosal immune mucosal immune systemsystem

• The mucosal response The mucosal response to infections and to infections and regulation of mucosal regulation of mucosal immune responsesimmune responses

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The mucosal response to infection and regulation of mucosal The mucosal response to infection and regulation of mucosal immune responsesimmune responses

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The mucosal response to infection and regulation of mucosal The mucosal response to infection and regulation of mucosal immune responsesimmune responses

Many enteric pathogens need to exploit host mechanisms as part of their invasive strategies

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Shigella flexneri Shigella flexneri infects intestinal epithelial cells infects intestinal epithelial cells triggering activation of the NFkB pathwaytriggering activation of the NFkB pathway

The mucosal response to infection and regulation of mucosal The mucosal response to infection and regulation of mucosal immune responsesimmune responses

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The mucosal response to infection and regulation of mucosal The mucosal response to infection and regulation of mucosal immune responsesimmune responses

NOD: nucleotide binding oligomerization domain

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The mucosal response to infection and regulation of mucosal The mucosal response to infection and regulation of mucosal immune responsesimmune responses

Intestinal pathogensBacteriaVirusesParasites

induce inflammation

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Entry of nonpathogenic antigens Entry of nonpathogenic antigens e.g. food proteinse.g. food proteins

Mucosal ToleranceMucosal Tolerance

The mucosal response to infection and regulation of mucosal The mucosal response to infection and regulation of mucosal immune responsesimmune responses

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The concept of mucosal tolerance. Prolonged

mucosally administered antigens induce both systemic

and mucosal unresponsivenessto the same Ag when

challenged in the presence of adjuvant.

The mucosal response to infection and regulation of mucosal The mucosal response to infection and regulation of mucosal immune responsesimmune responses

2 weeks later

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The mucosal response to infection and regulation of mucosal The mucosal response to infection and regulation of mucosal immune responsesimmune responses

Proposed dose-dependent

mechanisms of oral tolerance.

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The healthy intestine contains large quantities of bacteria but does not generate productive immunity against them

The mucosal response to infection and regulation of mucosal The mucosal response to infection and regulation of mucosal immune responsesimmune responses

Metabolism of dietary constituents

Degrading toxins

Produce vitamin K & short chain fatty acids

Maintaining epithelium

Compete the pathogens

Inhibit pro-inflammatory signals

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Clostridium difficileClostridium difficile infection after treatment by infection after treatment by antibioticsantibiotics

The mucosal response to infection and regulation of mucosal The mucosal response to infection and regulation of mucosal immune responsesimmune responses

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The mucosal response to infection and regulation of mucosal The mucosal response to infection and regulation of mucosal immune responsesimmune responses

Mucosal DC regulate the induction of tolerance and immunity

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Commensal bacteria can prevent inflammatory responsesCommensal bacteria can prevent inflammatory responsesin the intestinein the intestine

The mucosal response to infection and regulation of mucosal The mucosal response to infection and regulation of mucosal immune responsesimmune responses

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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.

The mucosal response to infection and regulation of mucosal The mucosal response to infection and regulation of mucosal immune responsesimmune responses

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The mucosal response to infection and regulation of mucosal The mucosal response to infection and regulation of mucosal immune responsesimmune responses

The mucosal immune system must maintain a balance between The mucosal immune system must maintain a balance between protective immunity and mucosal tolerance to a large number of protective immunity and mucosal tolerance to a large number of different antigensdifferent antigens

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Celiac disease a breakdown of Celiac disease a breakdown of oral toleranceoral tolerance

The mucosal response to infection and regulation of mucosal The mucosal response to infection and regulation of mucosal immune responsesimmune responses

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The mucosal response to infection and regulation of mucosal The mucosal response to infection and regulation of mucosal immune responsesimmune responses

Parasites

Most helminths can induce both protective (Th2) and pathological (Th1) immune responses

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The mucosal response to infection and regulation of mucosal The mucosal response to infection and regulation of mucosal immune responsesimmune responses

Giardia lambliaGiardia lamblia

• Production of antibodies

• Infiltration of mucosa by effector cells

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The mucosal response to infection and regulation of mucosal The mucosal response to infection and regulation of mucosal immune responsesimmune responses

Cryptosporidium parvum & T. gondiiCryptosporidium parvum & T. gondii

• Intracellular pathogens• Require CD4Th1 and CD8 T cells to

clear them

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The mucosal response to infection and regulation of mucosal The mucosal response to infection and regulation of mucosal immune responsesimmune responses

Chronic infections of intestinal helminthsChronic 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

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The mucosal response to infection and regulation of mucosal The mucosal response to infection and regulation of mucosal immune responsesimmune responses

Protective and pathological responses to intestinal helminthsProtective and pathological responses to intestinal helminths

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The mucosal response to infection and regulation of mucosal The mucosal response to infection and regulation of mucosal immune responsesimmune responses

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