Mucosal immunity is specialized to prevent responses to harmless substances while mounting responses to pathogens. The mucosal immune system includes gut-associated lymphoid tissue (GALT) such as Peyer's patches. GALT uses innate mechanisms like mucus and defensins and adaptive responses including IgA and T cells to prevent microbial invasion while tolerating commensal bacteria. Dendritic cells sample antigens and induce regulatory or effector T cell responses depending on the antigen. Secretory IgA transported across the epithelium provides frontline protection for mucosal surfaces.

1. Mucosal immunity
( Regional immunity )

2. How mucosal immunity is very specialized
than systemic immune system?
By two Challenges (functions )
• Active immune response to pathogenic organisms.
• Regulatory functions : that serve to prevent
responses to nonpathogenic microbes (commensal
bacteria, microbiota ) and foreign substances (ex.
Food molecules )

3. regional immune system

5. GALT
Cells and functions
• General immunity Function?
•  prevents microbial invasion, underlying
connective tissue
•  mediate immune responses to organisms
that do invade through the epithelium
•  prevent impair barrier by inflammatory
response

6. GALT components

7. Peyer’s patches,
• Found mainly in the distal ileum,
• Peyer’s patches have the structure of lymphoid
follicles,
• with germinal centers containing B lymphocytes,
follicular helper T cells, follicular dendritic cells,
and macrophages.
• Its unencapsulated but organized secondary
lymphoid tissues just under the epithelial barrier.

8. 1. Innate immune protection
Mechanisms :
1. Secrete mucus, Glycocalyx.
2. produce α-defensins, , β-defensins
3. produce C-type lectins
4. Activate Innate lymphoid cells
5. produce proteins that form tight junctions
which block the movement of microbes
between the cells into the lamina propria

9. • 1. Mucins ;
1. a single layer,
2. its function prevents microbes from contacting with small
intestine epithelial cells
• Most in intestinal layer is composed of MUC2,
• Glycolipids with mucins form  Glycocalyx
• 2. Glycocalyx;
1. glycolipids is coated the apical surface of gastrointestinal
epithelial cells
2. It Function prevent microbial contact
1. Mucus

10. • Increases in mucins production
• By
1. cytokines (IL-1, IL-4, IL-6, IL-9, IL-13, tumor
necrosis factor [TNF], and type I interferons)
2. neutrophil products (such as elastase),
3. and microbial adhesive proteins.

11. 2. α-defensins
• Defensins are peptides produced by intestinal epithelial
cells that exert lethal toxic effects on microbes
• causing loss of integrity of their outer phospholipid
membranes of microbes
• including human defensin 5 (HD5) and HD6
• produced by Paneth cells response to IL-1 or invasive
bacteria.
• neutrophil granules are rich in α defensins
• In the colon, β-defensins are epithelial cells in the large
intestinal crypts,
• which likely contribute to their antimicrobial functions in
the setting of infections of the bowel wall.

12. Paneth cells and epithelial cells C-type lectins = (REGIII)
• Paneth cells and other epithelial cells of the
intestine also secrete C-type lectins called
regenerating islet-derived proteins (REGIII),
• Function which block bacterial colonization
of the epithelial surface.
secrete
3. C-type lectins = (REGIII)

13. TLRs
• Toll-like receptors (TLRs)
• NOD like receptors (NLRs)
• Its recognize PAMPs molecules of Ag
• On or in intestinal epithelial cells and lymphoid cells (as DCs)
• Ligation with Ag can:
1. increase strength of tight junctions
2. Give signal to increases intestinal epithelial motility and
proliferation.
3. Give signal to secretion of defensins, REGIII lectins, and IgA,
• but also limit inflammatory responses to commensal
bacteria.

14. TLRs
• TLR2 ( peptidoglycan or lipopeptides)
• TLR4 (LPS)
• TLR5 (flagellin)
• TLR6 (lipopeptides)
• TLR7 (ssRNA)
• TLR9 (CpG DNA)

15. TLRs
Out lecture

17. 2. Adaptive immune response
• 1. sampling Ag by APCs (DCs, Macrophages..)
or across through M-cells
• 2. Differ if it pathogenic or nonpathogenic Ag
by TLRs
Regulation
(tolerance )
4. Class switching Produce IgA
5. Pass IgA to lumen
6. Lymphocyte Homing to blood
3. Presenting to B, naïve T cells

18. M cell
•induction of response (Ag Uptake)
Take up antigen by endocytosis and phagocytosis across the M cell do vesicles ,
there where are handed to DC
1. M cells :

19. 2. Dendritic cells
• Capture antigen from lumen
• 1. Presentation of antigen to
mesenteric lymph nodes
• 2. or present Ag to T-cells
• An essential link between
innate and adaptive immunity
A. extend dendritic processes, so as Macrophages
B. sample antigens that derived from lumina through the epithelial barrier.
Sampling Ag
Some dendritic cells
•induction of response (Ag Uptake)

20. 2.A pathogen Dc  Effector T cell
• Dendritic cells
• 1. Antigen-sampling DCs extend dendritic processes
between intestinal epithelial cells into the lumen to
sample antigens
• 2. and then migrate to mesenteric lymph nodes,
• 3. where they initiate activation and differentiation
of pro inflammatory effector T cells.
• 4 . These DCs express the CD11b+ integrin chain and
the CX3CR1 chemokine receptor

21. 2. B nonpathogenic Ag Dc  Treg
• Other Dendritic cells
• 1. present in the lamina propria, which
express the integrin CD103,
• 2. present antigen to naïve T cells and induce
there differentiation of regulatory T cells, in
part by secreting TG F-B and retinoic acid (RA)
• The regulatory function of these DCs
depends on factors secreted by intestinal
epithelial cells

22. FIGURE 13-4 DCs in the intestinal mucosa. 2012

24. Regulation of Immunity in the Gastrointestinal
Tract by Regulatory T Cells and Cytokines
• Both retinoic acid and TGF-β promote FoxP3
expression and inhibit the generation of Th1 and
Th2 cells
• Treg produce immunosuppressive cytokine IL-10.
• Several cytokines, including TGF-β, IL-10, and IL-2,
play crucial roles in maintaining homeostasis

25. No immune responses to commensal bacteria
Tolerance
Lack danger signal
(no inflammation)

26. Oral Tolerance
• Oral Tolerance : a mechanism for prevention
harmful immune responses to harmless antigen
such as food
• Induction of anergy of Ag-specific T cells
• Clonal deletion of antigen-specific T cells
• Producing immunosuppressive cytokines ( IL-4,
IL-10, TGF-B)

27. 4. In T-dependent IgA class switching
• dendritic cells capture bacterial antigens
• delivered by M cells and migrate to the interfollicular
zone, where they present antigen to naive CD4+ T cells.
• The activated T cells differentiate into helper T cells
• B cell class switching to IgA is stimulated through T cell
CD40L binding to B cell CD40, together with the action
of TGF-β.

28. In T-dependent IgA class switching

29. • T-independent IgA class switching involves
dendritic cell activation of IgM+ B cells, including B-
1 cells.
• TLR ligand–activated dendritic cells secrete
cytokines that induce IgA class switching, including
BAFF, APRIL, and TGF-β.

30. • It is Isotypes (A1 and A2) are tissue-specific
• J-chain( joining chain)
• Secretory component (five domains)
Secretory IgA
Critical features of Secretory IgA
•They are resistance against common intestinal proteases
.
• can not interact with compliment or cells in and cause
inflammation Secretory Component
(five domains)
J chain
organization of mucosal immune system

31. Transported IgA across epithelial cell
• IgA produced by plasma cells in lamina
propria
• Produced as dimer covalently held together
by J chain
• Transported by poly-Ig receptor
• Complex is endocytosed into epithelial cell
and transported to luminal surface
• Poly-ig receptor is cleaved Secretory
component

32. Transport of the sIgA across the mucosal
epithelium into lumen

33. T cell Mediated immunity
• CD8+ Predominant
• Lamina propria T cells are mostly CD4+
• 10 % are γδ T cells
• Th17 : its presence dependent on colonization of
certain bacteria
(play a special role in maintaining mucosal epithelial
barrier function because of the actions of the two
signature cytokines they produce, IL-17 and IL-22)
• Th2 : mucus secretion and smooth muscle contraction
• Treg : promoted by CD103+ DC to

34. • Transforming growth factor beta = TGF-β
• Thymic stromal lymphopoietin (TSLP) is a
protein belonging to the cytokine family. It is
known to play an important role in the
maturation of T cell populations