dendritic cells/cosmetic dentistry courses

INDIAN DENTAL
ACADEMY
Leader in continuing
Dental Education
www.indiandentalacademy.com

• Robbin’s Basic Pathology
• 8th edition
• Dendritic cells and the control of immunity
Jacques Banchereau & Ralph M. Steinman
• Fundamental Immunology
•4th edition William E.Paul
• Wheater’s Functional Histology
References:

• At the end of the seminar the learner should be
able to describe:
– What are Dendritic cells(DCs)..
– Development of Dendritic cells
– Forms & Distributions of dendritic cells
– Features of a Mature Dendritic cells
– Role of DCs in immunity
– Capturing of Ag by immature DCs
– Migration of DCs and its maturation
– Dendritic cells and B lymphocytes
Learning objectives :

 Dendritic cells are antigen-presenting cells (APCs)
 First visualized as Langerhans cells (LCs) in the skin in
1868.
 Dendritic cells (DCs) referred to as“Professional”APCs.
 Because :
 Principal function of DCs is to present antigens,
and
Only DCs have the ability to induce a primary immune
response in resting naive T-lymphocytes.

To perform such functions , DCs must capable of
capture antigens,
Processing antigens,
Display large amount of MHC peptide complex at
their surface
Upregulate their costimulatory molecules and
migrate to lymphoid organs.
 DCs also play a role in the maintenance of B cell
function and recall responses.
 Thus, DCs are critical in the establishment of
immunological memory.

 Dendritic cells progenitor are present in bone marrow.
Small CD34 + subset of Haemopoietic progenitor give rise
to DCs.
Both c-Kit ligand & flt-3 ligand (Trans membrane protein of
stromal cell) bind to DCs progenitors stimulate them to
form functional DCs.

 GM-CSF and IL-3 (product of activated T lymphocytes)
enhance DC differentiation.
TNF and CD-40L block the granulocytes differentiation
pathway of precursor cells and stimulate final maturation
of DCs.

 Different type of dendritic cells (DCs) were found in
our body
 They are distributed through out the body in a way
that
 It maximizes antigen capture
and
Maximizes binding and activation of T cell

 Different forms of dendritic cells were found in our
body are
 Interdigitating cells
 Veiled cells
 Langerhans cell
 Interstitial dendritic cells

In the lymph organs cells with dendritic morphology
occurs as two functionally distinct types
 Interdigitating dendritic cells (IDCs)
 Follicular Dendritic cells (FDCs)

Interdigitating dendritic cells (IDCs):
 Lymphoid organs are rich source of APCs
 They are abundant in T cell areas ( Paracortical area) ; also
called Interdigitating Dendritic cells (IDCs)
 These cells are large cells
 Having extend numerous processes between T-cells

Para-cortical region of lymph node

 Cytologic features of IDCs are similar to those of
typical DCs
 But many description of IDCs liken them to be
Macrophages
Interdigitating dendritic cells (IDCs):
Dendritic cells Macrophages
•Lack numerous
phagosomes and lysosomes
•Abundant phagosomes
•Perinuclear spot of
lysosomal acid
phosphatase
•Abundant acid
phosphatase

Functionally these cells are another type of dendritic
cells
Found in Lymphatic organs
Located in the germinal centres of the Spleen and
Lymph node
Follicular dendritic cells (FDCs):

Follicles in Lymph node

These cells bears receptors for the
 Fc tail of IgG
For complement proteins
And hence efficiently trap the antigen bound to
antibodies & complements

Thus these FDCs play a critical role in establishing
the immunological memory by
• Displaying antigen to activated B lymphocytes in
lymphoid follicle
• Promoting secondary antibody response

These cells do not take up stains in routine H & E
staining.
 But their dendritic processes can be demonstrated
by using special antibodies to IgM which is trapped
on plasma membrane.

Veiled cells :
Infectious agent & other antigens use afferent lymphatics
to gain access to draining lymph node.
Typical dendritic cells are also found in afferent
lymphatics.
These cell have large motile processes so called veiled
cell.

Langerhans cells (LCs) :
As a medical student these cells had described by
Paul Langerhans. as a peculiar set of cells in the skin.
 Bone marrow derived
Express features of WBC or Leukocytes
Fc receptor
MHC II

LCs were identified as a active cells in epidermis for
presenting antigens to primed T cells.
Langerhans cells are immature DCs as it lacks
High level of MHC II (On cell surface)
Fc Receptors
Non specific esterase
Antigen F4/80

These cells are mobile and non adherent
Langerhan's cell were identified by electron microscopy
using a Birbeck Granules as a marker.
Birbeck Granules

 Birbeck Granules
Tennis racket appearance
Racket form by membrane bound vacuole
Handle form by tight approximation of membrane
Express antigen recognise by Lag-1 monoclonal
antibody
Some times these granules were acquired by IDCs in
some allergic conditions.

Interstitial Dendritic cells:
 Most organs except BRAIN have MHC II rich DSc within
the interstitial spaces ; that are drained off by afferent
lymphatics.
e.g-
• In heart between muscle fibers
Only these DCs directly stimulate Naive B-cells to make
antibodies

Dendritic cells at other body surfaces :
Cells similar to epidermal LCs are found in all stratified
squamous epithelia.
e.g-
•Vagina
•Cervix
•Anus
•Pharynx
•Eosophagus
•Airways of lungs
•Intestine
•Iris
•Cilliary body

 Mucosal lymphoid tissues are lymphoid organs that are
found in most of the body surface other than skin
especially the gut.
In small intestine – Payers Patches
Nasopharynx – Adenoids and palatine tonsils of
Waldayers ring

 Numerous DCs are present just beneath these mucosal
lymphoid organs.
 Because this epithelium also contains specialized
transporting M cells
 Infectious agent and antigens move from gut or lumen
or pharynx directly in to the network of DCs through
these M cells

Mature Dendritic cells
In situ, as in the skin,
airways and lymphoid organs,
DCs are stellate.(a)
When isolated and spun onto
slides, DCs display many fine
dendrites.(b)
DCs in a sheet of epidermis (MHC II stain)
in cytospins stained for surface MHC IIwww.indiandentalacademy.com

When looked at with an electron
microscope, the processes are long
(>10µm) and thin, either spiny or
sheet-like.(c)
When alive and viewed by phase-
contrast microscopy,
DCs extend large, delicate
processes or veils in many
directions from the cell body(d)
By scanning electron microscopy
In the live state by phase-contrast microscopy.www.indiandentalacademy.com

These processes bend, retract and re-extend in a non
polarizing fashion.
Actin cables are scarce.
Terminally differentiated or mature DCs can
Readily prime T-cells.
Initiate immune response by interacting with other
cells:
• B-cell – anti-b formation
• Macrophage – cytokine release
• Target cell – its lysis

 Few DCs are required to evoke T-cell response.
One DCs evoke almost of 100-3000 T-Cells
MHC products and MHC- Peptide complexes are 10 -100
times higher than other APC like B-cell and Monocytes
DCs resist the action of IL-10, but also it synthesize high
levels of IL-12 so that it enhance both
innate immunity (NK cells)
acquired immunity (B & T -cells)

DCs also express many accessory molecules that
interact with receptor on T cell to enhance adhesion and
signalling
CD-58
CD-54
CD-86

DCs can stimulate outgrowth and activation of variety
of T cells
DCs
MHC- I
MHC- II
CTLs ( T8 )
CD8
CTLs ( T8 )
CTLs ( T8
)
CTLs ( T8 )
T-helper
cell
CD4
IL-12
IFN-γ producing
Th-1 cell
IL-12
Macrophage
(Antimicrobial activity)
NK cells
IL-4
Th-2 Cells
(IL-4 & IL-5)
• Act. Eosinophil
• B-cell  Anti.B

Relationship of DCs and T-cells seems to be two way
rather than one way i.e.
DCs also responds to Tcells
CD-40 and TRANCE/RANK receptor are present on DCs
These receptor binds to TNF family protein present on
activated T-Cells and Memory T-Cells.
Leads to increased DCs survival in the lymphatic organs.

DCs are potent stimulator of B & T – Lymphocytes.
B cell recognize the native antigen directly through
their B-cell receptors
T lymphocytes, need the antigen to be processed and
presented to them by an APC.
The T-cell antigen receptors (TCRs) recognize fragments
of antigens bound to molecules of the major
histocompatibility complex (MHC) on the surface of an
APC.

 Through out this all process the DCs changes its shape
and expression molecules .
 It becomes mature from immature state.

An example of a pathogenic molecule that will induce DCs maturation is
lipopolysaccharide (LPS); TNFa, GM-CSF are examples of cytokines, and CD40L
is an example of a T-cell ligand that binds CD40 on DCs. IL-10 can inhibit
maturation www.indiandentalacademy.com

Antigen capture – Immature DCs
Migration of DCs ( Periphery – lymphatic
organs ) along with maturation of DCs
Antigen Presentation to T-cells

Antigen Capture by Immature DCs
In most tissues, DCs are present in immature state.
These cells are unable to stimulate T cells
And also lack requisite accessory signals for T cell
activation.(CD40, CD54, CD86)
These cells are extremely well equipped to capture
antigen.

Sentinel position of immature DCs are skin surface or
epidermis .
Humans have 10 9 epidermal DCs – Langerhans cells
Located above the basal layer of proliferating
keratinocytes.

Immature DCs are also isolated from
But these cells lack the LCs specific marker
(E-Cadherin; Birbeck granules; Lag-1)
• Blood
• lung
• spleen
• heart
• kidney
• B- & T-cells of tonsil

What makes DCs such a good APC?
DCs have several features that allow them to capture
antigen.
1. They take up particle an microbe by phagocytosis
2. They form large pinocytic vesicle in which extracellular
fluid and solutes are sampled.(Micropinocytosis)
3. Express receptor that mediate adsorptive endocytosis
including
• c-type lectin receptor
• MMR (Macrophage mannose receptor)
• DEC-205
• Fcγ& Fcε receptor.

 Antigen enter the endocytic pathway of DCs
 DCs produce large amount of MHC class II– peptide
complex at single brief stage of its life
 This is because DCs contains MHC class II rich
Compartments (MIICs).
 These MIICs edit and enhance peptide binding to MHC
class II then send to cell surface.

 To generate cytotoxic T killer cells, DCs have to present
antigen peptide complex to MHC class I molecule to CD8
expressing T cells
 This mechanism is relatively straight forward somtimes if
DCs infect itself; however T8 cell activity for transplanted
organs and tumor derived antigen is not yet clear.

DCs
Virus
DCs cell surface
proteosomeAntigen Capture by Immature DCs

Migration and maturation of DCs
 After activation, DCs travels to lymphoid tissue
 Mean while it get matured via variety of factors
 Whole bacteria ; its cell wall components
 Cytokines like
 IL-1
 GM-CSF
 TNF-α
Inflammatory mediator

 In blood there are two subsets of precursor DCs
 CD11c + & CD11c
-
Both enter the lymphoid tissue via HEV
(high endothelial
venule)
By virtue of CD49d-β1 integrin. to different final
destination
CD11c + to B cell area
CD11c
- to T cell area

GM-CSF
TNF-α
IL-1
Are known to modulate DC movement and maturation

DCs and B lymphocytes
DCs are known to have major effect on B cell growth
and immunoglobulin secretion.
DCs activate and expand T helper cells which in turn
induce B cell growth and antibodies production.
But there is also a direct B cell and DCs interaction is
present.

Naive B cells respond uniquely to non-LC type Interstitial
DCs
These DCs secrete soluble factors including IL-12 and
stimulate antibodies secretion from the B cell
These B cells actually already been stimulated by CD40-L on
activated T-cells

DCs also regulate the immunoglobulin class switching of B-
cell that have been stimulated by T-cell
IL-10 and TGF-β induce secretion of IgA1
IgA2 requires direct contact between B-cell and DCs

dendritic cells/cosmetic dentistry courses

Recommended

Recommended

More Related Content

What's hot

What's hot (20)

Similar to dendritic cells/cosmetic dentistry courses

Similar to dendritic cells/cosmetic dentistry courses (20)

More from Indian dental academy

More from Indian dental academy (20)

Recently uploaded

Recently uploaded (20)

dendritic cells/cosmetic dentistry courses