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Perio Craze
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Introduction
The immune system
Generates variety of cells and molecules
capable of specifically recognizing and
eliminating an apparently limitless variety of
foreign invaders.
Exquisitely adaptable dynamic network
which is complex.
Complex System
Cell “Cross-Talk”
Cytokine
Group of intercellular signaling low
molecular weight proteins
Provides a network controlling local and
systemic immune and inflammatory
responses
Affects wound healing, hematopoiesis and
other biologic process.
Definitions
Encyclopedia of Immunology
Offenbacher 1999
TERM
Classification on Biologic
Activities
Affecting macrophages:
Migration inhibition factor
Macrophage activity factor
Macrophage aggregation factor
Macrophage chemotactic factor
Macrophage resistant factor
Affecting lymphocytes:
Blastogenic or mitogenic factor
T-cell growth factor
B-cell growth factor
Affecting granulocytes:
Chemotactic factor
Colony stimulating factor
Inhibition factor
Classification on Biologic
Activities
Affecting cultured cell:
Lymphotoxin
Gamma interferon
TNF
Colony inhibitory factor.
Producing in vitro effects:
Osteoclast activating factor
Transfer factor
Procoagulant factor
Nissengard Newman
Classification
First group:
Cytokines which serve as mediators of innate
immunity E.g. α ,β, interferon, TNF, IL-6
Second group
Cytokines that regulate the growth &
differentiation of lymphocytes. E.g. IL 2,4 TGF β
Third group
Cytokines that regulate hematogenous activity
E.g Gamma CSF, IL-3,7
Fourth group
Cytokines that share the common property of
being activation of inflammatory cell function
e.g gamma interferon
Jan Lindhe’s Classification
Pro inflammatory cytokines
E.g. IL -1,6, TNF α – stimulates bone
resorption
Chemotactic cytokines
E.g. IL-8 ,16
Lymphocyte signaling cytokines
Released by Th 1- IL 2, IFN
Released by Th 2- IL4,5,10,13
Based on Characters of
Cytokines
Cytokines that regulate lymphocytes
E.g.: IL 2,4
2. Cytokines that activate
inflammatory cells
E.g.: IFN gamma, TNF beta
3.Cytokines that stimulate
hematopoiesis
E.g.: IL3,7
4.Colony stimulating factor
E.g.: CSF
Biological Properties
Overview of Cytokine
Production
Pleiotropy
Redundancy
Synergism and Antagonism
Cascade Induction
Cytokines Vs Hormones
Cytokines Vs Growth
Factors
NKR
K
L R
T
I
F N
- D
IL 2
R 1 C
TL
Macropha
ge TNF, IL-
1,
Neutroph
ils
Immuno Regulatory
Cytokines
TGF Beta
TGF beta
Humans expresses 3 forms: TGFβ
1,2,3
These are the products of separate
genes, but they all bind to 5 types of
high affinity cell surface receptors
Type I,II - receptors transducesignals
Type II :
IFNs ( immune interferon) E.g.IFN γ
Interferon α,β
IFN α – Secreted by lymphocytes
Inhibits viral replication in uninfected cells
IFN β – Secreted by fibroblasts
Also inhibits viral replication in uninfected
cells
Interferon Gamma
Secreted by T H1 ,T C ,NK Cells
Inhibits viral replication in uninfected
cells
Enhances activity of macrophages
Oncostatin
Pleitropic cytokine that belongs to the
Interleukin 6 group of cytokines
Secreted by macrophages, T cells
Inhibits growth of tumor cells
Induces hepatocytes to synthesis
acute phase protein
Stimulates growth of Kaposi’s sarcoma
RANTES
Regulated upon Activation Normal T cell
Expressed and Secreted.
Source: T Lymphocytes, Platelets
Chemo attracted cells: monocytes,T-
lymphocytes,basophils, eosinophils, mast
cells.
Other activities
Macrophage activation
Integrin expression by T cells
Chronic inflammation
Basophil degranulation
Cytokine Assays
Cytokine Assays
ELISA
Coat well of micro titreof place with anti cytokine
antibody
Block un occupied sites with protein
Add cytokine (the cytokine will be captured by the
antibody)
Add enzyme conjugated anti cytokine antibody
(secondary) It forms a sandwich with the captured
cytokine .
Add chromogenic substrate .the enzyme generates
a colour whose integrity is proportional to the
amount of cytokine bound to the captured
antibody.
Optimal density of colour is measured
Immuno Radiometric
Assays
Bead coated with anti- cytokine
antibody
Add cytokine
Add iodinated anti cytokine
monoclonal antibody
It is sandwiched to capture cytokine
and because it is radio-labelled it is
detected radio metrically
Regulation of Cytokines
Receptor antagonists bind to a specific receptor
but do
not transmit a signal (competitive inhibition)
The extra cellular domains of cytokine receptors
can be
shed. They bend their cytokine in the fluid phase
and to stop the cytokine from reaching receptor on
cell membranes.
After the cytokine bind to receptors another
cytokine bind to the other receptor of cell and
produce opposite effects on the cell.
Some cells can express cytokine binding molecules
(deceptors) which specifically bind ligand but do
The Perio View
Monocytes / Macrophages
Macrophages constitute 5 to30% of
infiltrating cells in inflamed periodontal
lesions.
They produce cytokines IL
1,6,10,12,13,TNF ALPHA,IFNα
They produce a central role in production
of IL1 in inflamed sites.
Studies have shown that
periodontopathic bacteria such as P.g,
A.a,F.n induce expression of IL1 in mono
nuclear Cells.
Lymphocytes
Activated T cells with a helper CD 4
phenotype secrete a variety of
cytokines such as IL
2,3,6,9,10,13,15,TNF.
Cytokines are produced in large
numbers due to the numerous
lymphocytes in inflammatory
periodontal lesions produced
Gingival Fibroblasts
Abundant cells In periodontal tissues
Secretes IL 1,alpha,beta ,IL 6,TNF
alpha.
mRNA expression
Gingival fibroblasts lymphocyte
interaction may facilitate the cytokine
network in inflamed gingival tissues.
Gingival Epithelial Cells
Gingival epithelial cells play an important
role as the first barrier against offending
bacterial agents in periodontal pockets.
There is increased expression of IL 1
beta,6,8,TNF alpha in the activated
gingival epithelial cells lines.
So it has been speculated that epithelial
cells confronting periodontopathic
bacteria may initiate the recruitment of
immuno competent cells by secreting
these cytokines.
Endothelial Cells