Mucosal Immune System

Jajah Fachiroh, Rina Susilowati

Deparment of Histology and Cell Biology

Faculty of Medicine Universitas Gadjah Mada
jajahfachiroh@yahoo.com

Basic Course on immunology

Yogyakarta, 23-25 April 2012

1. Introduction

2. Anatomic feature
3. Effector mechanism
4. Immunoregulatory environment

CONTENTS

Introduction
The importance of mucosal immunity

Mucosal surface exposed continuously to large amount of pathogens

Enormous area to be protected

Mucosal infections are one of the biggest health problems

Mucosa-associated Lymphoid Tissue

(MALT)

NALT
Waldeyers
ring
BALT
GALT
Lymphoid
tissue of
urogenital
tract

Primary lymphoid
organs
Secondary lymphoid
organs
6

Anatomic feature
Emphasizes on GALT

Epithelium provides host direct protection from luminal microbes

(a) microvillar extension

(b) epithelial-cell tight
junctions

(c) apically attached and

secreted mucins that form a
glycocalyx
(d) production of various
antimicrobial peptides
(e) M (microfold) cells overlie
Peyer's patches (f) to promote
uptake and transport of
luminal contents to
professional APC

(g).dendritic cell (DC) can also

extend dendrites between the
tight junctions of intestinal
epithelial cells to sample
luminal contents
David Artis, 2008 Nature Reviews Immunology 8, 411-420

Anatomic feature of mucosal immune system

In the gut, Mucosa-associated Lymphoid Tissue is located in

anatomically defines compartments

Peyers patches

Johannes Conrad Peyer

(16531712), a Swiss anatomist
9

Anatomic feature of mucosal immune system

Inductive site

MALT

Effector site

Lamina propria

Anatomic feature of mucosal immune system

GALT

Jejenum

Ileum

11

Anatomic feature of mucosal immune system

Substances & microorganism

taken up by M cells

12

The organization of the mucosal immune system

GALT

13

The organization of the mucosal immune system: dendritic cells

Effector mechanism
Immune response in GALT

Homing receptor determines the effector site

Lamina propria

Homing receptor determines effector site

The circulation of lymphocytes within the mucosal immune system is controlled

by tissue-specific adhesion molecules and chemokine receptors

Homing receptor determines effector site

Iwasaki, Annu. Rev. Immunol. 2007. 25:381418

Molecular control of
intestine specific
homing of
lymphocytes

Homing receptor determines effector site

The mucosal immune system contains large numbers of effector lymphocytes even in
the absence of disease

Efector cells in GALT : Intra epithelial lymphocytes

Intraepithelial lymphocytes
(IEL) type a & b

Epithelial cells
T cells
B cells

20

Efector cells in GALT : Intra epithelial lymphocytes

Intraepithelial lymphocytes type a (classical CD8 CTL;
heterodimer) recognize virus infected epithelial cells

21

Efector cells in GALT : Intra epithelial lymphocytes

Intraepithelial lymphocytes type b (non classical CD8
homodimer) recognize stress epithelial cells

effector cells in GALT : Dimeric IgA

IgA of the mucosal tissue
dimer linked by a J chain
IgA1:IgA2 = 3:2

IgA of the blood

Monomer
IgA1:IgA2 = 10:1

J-chains bind polymeric

immunoglobulin receptors
expressed by immature epithelial
cells at the base of intestinal crypts

effector cells in GALT : pentameric IgM may replace dimeric IgA

Brandtzeg & Johansen 2005.

Immunological Reviews 206: 3263

effector cells in GALT : secretion of dimeric IgA

Transcytosis of
IgA antibody
across epithelia
is mediated by
the poly-Ig
receptor
Once dimeric
IgA reaches
lumen, mucin
will bind
Secretory
component and
retains IgA

Secretory IgA has several functions in epithelial surfaces

Immunoregulatory mechanism
Commensalism

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
Compete the pathogens
Inhibit pro-inflammatory
signals

Musketeers Course October 2009

(Preidis & Versalovic , 2009)

29

Commensal bacteria prevent inflammatory responses

in the intestine (i.e. NFkB)

Comensal microorganisms induce production of

secretory IgA disable their penetration into the cell

31

Mucosal Dendritic cells regulate the induction of tolerance and immunity

The mucosal immune system must maintain a balance between protective

immunity and mucosal tolerance to a large number of different antigens

Immunoregulatory mechanism
Oral tolerance

The mucosal response to infection and regulation of mucosal immune responses

Oral Tolerance

Entry of nonpathogenic antigens

e.g. food proteins

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

Same theory offered to explain

oral tolerance
( as explained in comensalism)

Celiac disease: a breakdown of

oral tolerance

SUMMARY

THANK YOU

The mucosal response to infection and regulation of mucosal immune responses

Shigella flexneri infects intestinal epithelial cells triggering

activation of the NFkB pathway

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