Effects of the Immune System

Oral Defense Mechanism

-

mucosa
system • Beneficial:
Nuntana Aroonrerk

• Protection from Invaders

• Elimination of Altered Self -
cancer
-
• Detrimental:

Assoc.Prof. Dr. Nuntana Aroonrerk • Inflammation

• Damage to self (hypersensitivity or autoimmunity)

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Oral Mucosal
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Relationships with the host
 Host defense in the mouth:
immunity
 Epithelial cells:
 Barrier function;
-
non
-
specific
 Innate immunity - sensors (Toll-like receptors);
(C -

modo eprheiion

fracas
 Inflammatory mediators, antimicrobial peptides; II defend
: C
-

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- -

 Salivary antimicrobial factors;

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specify
 Mucosal antibodies (secretory IgA);

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Ag eserine DI
process
 Lysozyme: non
specific
Fluid phase

Irm
Pg

 Serous subsystem
Cleaves b-1,4 linkage between

(
N-acetylglucosamine and N-acetylmuramic acid in
peptidoglycan of cell wall

 o
Nonspecific factors (lactoferrin, lysozyme and g
Lactoferrin (LF): Iron binding protein-sequester (กักเก็บ) free
 -

iron, so remove essential substrate required for bacterial growth.

peroxidase) -

Antibacterial action: LF bind to specific receptors or LPS on cell

 Nonviscosity small peptide, ‘histatins’ surface or bacterial wall of microbes, then the oxidized iron part of
LF oxidizes bacteria via formation of peroxides. This affects the
 Antigen-specific secretory IgA membrane permeability & results in the cell breakdown (lysis)
Antiviral activity: its diversion of virus particles from the target cells.
Many viruses tend to bind to the lipoproteins of the cell membranes
 Mucous subsystem and then penetrate into the cell. LF binds to the same lipoproteins
 Contain glycoprotein, ‘mucin’ (viscosity) thereby repelling the virus particles.

• Peroxidase (lactoperoxidase)
Catalyzes the reducion of H2O2 to water antioxidant

specific
Non
Histatin {HUH
W N

 antimicrobial & antifungal proteins , & play a role in wound-

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Defensins (D)
closure.  Defensin: small cysteine-rich cationic proteins,
including vertebrate and invertebrate animals, plants,and fungi.
 Found in serous fluid secreted by Ebner's glands, salivary glands
 Host defense peptides, either direct antimicrobial
viral bacteria fungal
at the back of the tongue, & produced by Acinus cells.

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activity, immune signalling activities, or both. D are variously active
 Offer some early defense against incoming microbes.
against bacteria, fungi and many enveloped and nonenveloped viruses.
 3 major histatins: 1, 3, & 5 (contains 38, 32, and 24 amino acids).
 Typically 18-45 amino acids in length with disulphide bonds.
Histatin 2 is a degradation product of histatin 1, & all other a rein
#
 In animals, D are produced by cells of the innate immune
histatins are degradation products of histatin 3
- system & epithelial cells, whereas in plants, fungi D are produced by a
 Antifungal report: such as C. glabrata, C. krusei, Saccharomyces wide variety of tissues. An organism usually produces many different
cerevisiae, & Cryptococcus neoformans defensins, some of which are stored inside the cells (e.g.
 Histatin's anti-fungal Action: by the release of the fungal's in neutrophil granulocytes to kill phagocytosed bacteria), and
intracellular component through the disruption of the fungus
-
others are secreted into the extracellular medium.
plasma membrane. They also work against yeast, by binding to  For those that directly kill microbes, their mechanism of action
-
the potassium transporter and facilitating in the loss of azole- varies from disruption of the microbial cell membrane to
resistant species.[12] metabolic disruption.
 ::
Salivary Proteins Mucin
÷ ::
'
:
:::

 Statherin – potent inhibitor of calcium phosphate

precipitation 
go.me
• Salivary mucins - 2 genetic types, MUC5B and MUC7
mostly MUC5B mucins, anchored to epithelial oral cells.

 Defensin –antibacterial, antifungal, antivial • physiochemical properties of mucins depend on glycosylation &
 Mucin- aggregate oral flora bacteria and prevent dental
caries
molecular weight wutdo A
-
ng acquired
i am

• MUC5B-role in forming adsorbed salivary film & resulting in low

=
 Calprotectin- act as calcium sensors and potent zinz
-
binder, also play role in tooth repair
friction response form disulfide bridging, hydrophobic forces and
interactions with proline-rich proteins (PRPs) and other lower
molecular weight salivary proteins (e.g. sIgA, lysozyme, histatins)

⇐
 This pellicle is involved in protection of oral mucosa against
abrasion, pathogenic microorganisms or chemical xenobiotics.

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Sessile components Sessile components

①
Epithelium

 Desquamative mechanism fans
soon ugh as
Fibroblast & connective tissue -


Physical barrier
participate in mucosal defense by providing


 =
Lysosomal leucocytes
cytokines and response to signals from
 -
Connective tissue
 Langerhans cells, Interepithelial lymph, Dermal
⇐
mobile phase cells
dendrocytes, Mast cells
-

 Peripheral DC: can process and present Ag and

take Ag to present to T cells in the lymph node
 Mast cells can recruit cells from mobile phase
 Emffins goo Bacteria
whine
assorted

§
io¥%
.

(A) In biofilm, bacterial metabolism of sucrose causes a decrease in the local pH, leading to
C demineralization of the tooth structure.
(B) Presence of mucins in sucrose-supplemented growth medium decreases S. mutans
attachment & biofilm formation on tooth surface by maintaining S. mutans in the
planktonic state. -
-

9 10

emphasises
Mobile phase
- C
Extraoral lymph node
armature:Ygm
Lymph capillaries larger
 Consist: neutrophils, monocytes, oral mucosa, gingivae lymphatics Other sites
T cells, B cells, NK cells pulp of teeth
- -

Lymph vessels

⇐
submandibular, submental
upper deep cervical,
retropharyngeal

Lymph nodes
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Ms wise 9
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lymphocyte
afro lymph MY
T cell ,

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mucosa

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Intra-oral lymph tissues
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 Not fully understood
 4 Types of lymphoid aggregations in mouth
 Tonsils in oral cavity C
 Salivary gland lymphoid tissue
 Gingival lymphoid tissue
Scattered submucosa lymphoid cells

C Tonsils
 Palatine tonsils
 Lingual tonsils
 Pharyngeal tonsils or
adenoid

pogey
penetrate
Ag from do
0907 Lingual tonsils whimsy
so

Palatine tonsils Towards egmpmcoim "

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Structure and role like palatine tonsils q -


 1 pair between oral cavity & pharynx
 Classical structure of lymphoid follicles  2 sides of lyngual
 B cells and perifollicular T cells
Pharyngeal tonsils or Adenoids

←Ag penetrates through covering epithelium (no efferent
lymphatics)
-
-

 Under pharynx, at nasopharynx

 Believed to guard the entry into the digestive and
respiratory tracts
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's

d.pro
present
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process Salivary gland lymphoid tissue

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M-cells  Lymphoid tissues nearby salivary gland or distributed
(microfold cells) within acini of salivary gland
E
Found in the
epithelium of  Found lymphocytes and plasma cells in a small clumps
dinged

!
palatine tonsil
crypt

=
in
Tons  Mainly with synthesis of secretory IgA
responsible for
luminal - antigen
uptake  Protect infection in salivary/salivary gland/adhesion of
microbes to mucosa/teeth
- also entry portal -
of pathogens one
ethane and 28

Gingival lymphoid tissue

 In gingival : found plasma cells,

lymphocytes, macrophages & PMN

 Important in immunological response to

dental plaque

25
 bacteria
di:&:&'s
Scattered submucosal lymphoid cells Saliva
=
 Found scattered in submucosal 

Mechanical cleansing
lysozyme


Leucocytes
Secretory IgA
 Defense mechanism -  Peroxidase  Buffering effect
If the anti-adhesion mechanism at mucosa is not  Lactoferrin  Ca and PO4 ion/Fluoride
effected, these cells were stimulated & proliferation
to protect the infection
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Detail

Antibody in Saliva

 IgA- most abundant in saliva

 IgA- monomer (found in blood)
- dimer found in the secretion
(J chain/secretory component)
call “Secretory IgA” (Fig 2- Sheet)

Secretory Immunoglobulin A (sIgA)

 IgA

 2 subclasses in humans
 co
IgA1- monomeric, predominant IgA in serum
 ~ 80-90% of total IgA -
in serum
 ~ 50-74% of total IgA in secretion

C
 IgA1 - degraded by IgA1 proteinase
-

 IgA2- polymeric, predominantly found in external 't

secretions. serum
 J-chain- required for formation of polymeric IgA
way,
= Loss of 13 aa in hinge region reduces susceptibility of
IgA2 to proteolytic cleavage.

hningeregismasieip:L:
 IgA2 is the evolution of IgA1

IgG: IgA Secretory IgA

§ §
'd
grounds  Mucosal secretions of IgA reaches adult
levels early (1 month to 2 years)
 Polymeric Ig receptor (pIgR) is
expressed on the basolateral surface of
epithelial cells and facilitates transport of
Ig. A
 Transport of IgA Through Epithelial Cells Specific protection - Secretory IgA system

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EET
 SIgA reduce microbial adhesion to enamel epithelium

:*
sit
* mum
 Protects the mucosa of penetration of antigens
 Immune complex - C’ activation

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Opsonization
upIgp


idk  Neutralization e.g. anti-virus, anti-toxin

god O 
-
Inflammation

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Gingival crevicular fluid

Books80k¥ ago leak so.
00am Gingival crevicular fluid
,

-
Serum like flow through junctional epithelium of gingiva
 T
Serum like secretion
 nonspecific
leucocytes: neutrophil (>80%), majority
 Flow rate 0.3 ul/teeth/hr

 Inflammation higher volume, higher area but flow rate

not higher Jonas annoy macrophage,

B cell, some T cells
-

 Healthy: pH C6.90 fo -


-
f
Periodontitis/gingivitis: pH 7.25-7.75 wenn  immunoglobulin
-

 Found Ig, complement…c’ fixation both alt and class pw  complement

 o
Most : IgG
enzyme ; lysozyme, protease, collagenase
imbueEos east on Eau 

→Minor : IgM, IgA
so
a
etc.
gas
Seram
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Pattern recognition receptor (PRRs) ligands
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 PRRs (on host cells) recognize conserved molecular structures
known as pathogen- or damage-associated molecular patterns
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Odours
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(PAMPs and DAMPs), PAMP found in microbes. DAMP
damage molecule occurs in host.
coarsens microbe now
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RBC
-

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 These PAMP motifs are specific to the microbes (“non-self”). room v
,

replicate
- -

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.

 One of the best characterized PAMP - LPS, a specific C

component of the gram –ve bacteria which is recognized by
Toll-like receptor TLR4
&
Greisen * recruiter
g 094
lymphdenmark

PAMPs examples
5

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 Glycans
 Lipoglycans such as lipopolysaccharide, gram- bact outer

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-

membrane
-

 Peptidoglycans such as bacterial muramyl dipeptide

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-

 b-1, 3-glucans from the cell wall of various fungi species

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 Proteins
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 bacteria flagellin

-
⇐
 Nucleic acids (RNA or DNA)
 Microbial nucleic acids
 µCMHC
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epithelium Gcp Tap

res kpif atorqqrueia indonhu

Mucosal Immune Regulation
 Mucosal Immune Regulation
 Several levels of mucosal immune regulation exist, via a #

complex interplay between innate/adaptive immunity  Mucosal cytokines: mucosal ‘accessory’ cells (DC,
 Nature of the antigen: PAMPs ligate PPRs on innate
mast cells, eosinophils, macrophages, NK cells,a-γδT-cells) release
preformed mediators and cytokines on antigen stimulation, priming
APC, upregulating MHC and co-stimulatory molecule
the micro-envoironment for a particular adaptive response shape
expression .hu
Tinier
*  Replicating rather than inactive microbes: more
 Such mediators can include suppressor cytokines such as IL-10
and TGFβ (e.g. Peyer’s patch DC make IL-10 but little IL-12,
assist- likely to induce productive immune responses
-

leading to Th2-type responses)→ Ab

paid

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- -

 Soluble antigens are handled differently by  DC antigen presentation and micro-environemtnal cytokines
released by rapid-response cells profoundly impact the immune
- -

tolerance pathways, which may explain the failure

Ast response shape (Th1-type cell-mediated immunity, Th2-type

.hn/-pr.gsoiling
rameelldead
of clinical oral/nasal immunisation using soluble
-

I:&:p:&
antibody-mediated immunity, or Treg-mediated tolerance) and
antigens outcomes
 APC: immature DC or non-professional APC (e.g.  IL-12 and IFNγ from activated macrophages can break
epithelia) lack co-stimulatory molecules, which may

Thingy .to?mofY
tolerance
lead to T-cell anergy or apoptosis
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fgtsoanomoorrroo stimulatory
sodas 918 notepaper

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DC in Mucosal Tolerance
oddDharma
..
-
 DC antigen presentation regulates tolerance through: deletion of
autoreactive T-cells, induction of anergy by immature DC (expressing low Esses
levels of co-stimulatory molecules), and induction and expansion of Treg -
opinion
 Humans have 2 major DC populations: CD11chi (myeloid DC or ‘mDC’) and
w
CD11clo (lymphoid/plasmacytoid DC or ‘pDC’)
 Activated DC influence the shape of the Th response, with Treg induced by
IL-10-producing subsets **a
f
-
 Steady-state (sampling of commensal bacteria or alternatively to self antigens or to proteins
intestinal DC may be conditioned by epithelial factors to
found in food products)
promote Treg, which promote IgA-secretory B-cell in the mesenteric lymph
nodes, also contributing to immunoglobulin-mediated immune exclusion
(ยับยังการทํางานของ B cells) (Figure 1A)
Jodo
 During epithelial invasion by replicating pathogens, on the other hand, PRR
activation enhances pro-inflammatory cytokine production and phagocyte
recruitment (incoming naïve DC are not conditioned, and encountering
pathogenic antigens thus leads to pro-inflammatory Th1 and Th17 responses) C
Cavani
Ewing:p
(Figure 1B) C
nwndrissoguronoailh "
.me woodgrain
's
inflamakm
Wasim mucosal Tolerance
Faramir Extracellular
-
Th ,
intracellular THE
Harry
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⇐
ascension

41