why need immunomodulators

Now, become
very popular & center of medicine
people realize the important of immune
system as a health center
environmental rich in infectors/pathogens
difficult to avoid from the infector

immunomodulators
Daily activity
stress
immune system disturbance
Herbal industry
develop plant as
immunomodulator
Deficiency immune system
HIV, bird flu, swain flu
Autoimmune disease:
SLE
Multiple sclerosis
Myasthenia gravis

need
immunomodulator

Immunomodulator is a substance that have

activity to regulate immune system

Regulate
normalize or optimize immune response

IMMUNOMODULATOR
(IDEAL) If administered to patient
immune system deficiency
can enhance immunity
Overactive immune system
can normalized

not booster
but normalize immune system

Immunsuppressive
Immunostimulation
Organ
Transplanted

IMMUNO Autoimmune MODULATOR

diseases:
SLE, RA,
MS, MG

Tolerogen

Block co-stimulation

Immune def
diseases:
HIV-AIDs,
bird flu,
Tumor,
Chronic,
Infectious disea

 Immunomodulator
is substance or biological product used in

immunotherapy to

stimulate,
potentiate, or
suppress

Immune response

Inhibit or enhance certain subclass

of immunocyte

IMMUNOMODULATORS
Immunostimulant
Substances that stimulate immunity
Antisera
antibodies
anti cobra venom
transient but instant protection
Vaccines
whole or part of infectious bacteria/virus
develop our own immunity
Cytokines
interferon, etc

maria immaculata iwo, sf itb

Immunostimulant
is a substance that could stimulate or enhance
immune system function

Vaccination/immunization ?
H. Wagner: paramunity

Complement
Lymphocytes

UNSPECIFICALLY
ACTING OF
IMMUNOMODULATORS

Granulocyte
lymphocytes

Macrophages

Microphagocytosis

Macrophagocytosis

T
T-helper

cells
T-suppressor
cells
Cytotoxic, NK
cells
Liberation of mediators
(i.e. interferon , interleukin,
interferon)
tumor necrosis factor,
protaglandins, O2 ,
lyzosomal enzymes, etc)

Liberation of lymphokines
(i.e, IL-2 or

Source of immunomodulators

Plant, animal, microbial (probiotics) or

as synthetic products
Low MW: alkaloid, steroid/terpenoid,
flavonoid,
quinine, dll
High MW: - Many polysaccharides
- Proteins
- Glycoprotein/lectins
- Nucleotide

Source of immunomodulator
So far,

no structure-activity relationships have been

found amongst low & high molecular weight
compounds.
The same substance can act as an
immunostimulant or as immunosuppressive
agent,
depending on the dose.

Compound having immunomodulatory effect

Compound/
class

Source

Immunomodulatory
activity
Activates T
lymphocytes and cause
them to secret
various lymphokines

Con A
Phytohemagglu
tinin (PHA)

Plant lectin

Lipopolysaccha
ride (LPS)

Microbial
product

Activates B
lymphocyte directly

Polysaccharide
(Zymosan,
lentinan,
pachymaran)

Higher plants,
fungi,
mushrooms,
seaweeds,
algae, lichens,
vegetables

Activates
macrophages, NK cells,
and cytotoxic T
lymphocytes and
having anti tumor
activity

Gallic acid and

protochatechuic
acids (Catechols)

Higher plant
stimulation of
phagocytosis

Higher plant
stimulation of
phagocytosis

BCG

Microbial

activates

Levamisol,
Isoprinosin,
Pentoxifilin,
simetidin,
thiabendazol,
DEC,
Thalidomid

Synthetic
immunomodulators

Biological Product:
Sitokin: interleukin, interferon, etc
Molecules that influence cellular metabolism,
i.e. PG Inhibitor,
enzyme inhibitor : bestatin, amastatin

Tolerogen

Immune cells still active

but no responsiveness to
an antigen

Immunosuppressants

* use to treat autoimmune

diseases

Prevent rejection of transplants

Treat autoimmune disease
CORTICOSTEROIDS
depress T-cells, antibody production &
macrophage responsiveness
CYCLOSPORIN
blocks T-cell proliferation
AZATHIOPRINE
suppress all immune cell proliferation
maria immaculata iwo, sf itb

immunosuppressive
Suppress immune system function:
inhibit DNA synthesis
Activated T suppressor cell
inhibit Th cell activity
inhibit humoral and cellular responses

immunosuppressant
Inhibitor T cell specific :
Inhibit Th cell activation and proliferation
Siklosporin, Takrolimus

Cytotoxic drugs
Block proliferation and differentiation of B
and T cells (Azathioprin, Siklofosfamid, Methotreksat,
Mikofenolat mofetil, klorambusil)

Glucocorticoid
Inhibit MHC expression and cytokines production ( IL1, IL-2, IL-6, T cells were not activated)
prednisolon

Monoclonal Antibodi
Muromonab CD3, Antithymosit globulin (ATG), Rho (D)
imunoglobulin

Glu.

CD

Ab
Siklo.,
Takrol.

CD

TOLEROGENS
Tolerogens are agents used to induce and

maintenance the immune tolerance, the active

state of antigen-specific non-responsiveness.

The induction of immunological tolerance is

necessary to avoid self-reactivity and useful for

organ transplantation process.

TOLERANCE
Tolerance refers to the specific immunological nonreactivity to an antigen resulting from a previous
exposure to the same antigen.

the most important form of tolerance is nonreactivity to self antigens,

it is possible to induce tolerance to non-self antigens.

When an antigen induces tolerance, it is

termed tolerogen.

Immunoprophylaxis
1. The way of acquired specific immunization
2. The classification and characteristics of
Artificial immunization
3. Biological product and their application

1. The way of acquired specific

immunization
Natural
immunization:
- heredity,
- non-specific

Active
immunization:
- natural,
- artificial

Acquired
immunization:
- acquired,
- specific

Passive
immunization:
- natural,
- artificial

DIFFERENT
DIFFERENT MODES
MODES OF
OF ACQUIRING
ACQUIRING IMMUNITY
IMMUNITY

Immunity

Acquired

Natural resistance
Passive
Artificial
Ab or Ig,
Immune cells

Natural

Adoptive
transfer of
immune cells
Active

Artificial

Placental transfer of IgG,

Colostral transfer of IgA

Natural

ACQUIRED IMMUNITY
Produced by prior exposure to
or via antibody production

ACTIVE IMMUNITY
Produced by antibodies that
develop in response to antigen
(immune response)

NATURAL ACQUIRED
Of PASSIVE IMMUNITY
Conferred by transfer
of maternal antibodies
across placenta or
in breast milk
PASSIVE IMMUNITY

Produced by transfer of
antibodies from another person

INDUCED ACTIVE
NATURALLY
INDUCED PASSIVE
ACQUIRED
IMMUNITY
IMMUNITY
ACTIVE
IMMUNITY
Develops after
Conferred by administration
Develops
after
Administration of
of antibodies to
exposure to antigen
antigen
combat infection
in
environment
to prevent disease

Immunity can be acquired through

active and passive immunization
Type
Active :
immunization

acquired through

Natural infection or unapparent

infection
Artificial infection:
vaccine, toxoid, attenuated

organisms
inactivated organisms
purified microbial
macromolecules

Passive
Immunization

Natural maternal antibody

Artificial immune serum

2. The classification characteristics of

Artificial immunization
Artificial active immunization:
Artificial passive immunization:
Comparison:

Artificial active immunization

Features:
1. The production of the effect: slow
(induction phase: 1-4weeks)
2. The persistent time of immunity: long
(months-years)
3. The application: specific prophylaxis
4. The agents: Ag (immunogen): vaccine,
toxoids

Artificial passive immunization

Features:
1. The production of the effect: fast

2. The persistent time of immunity: short (2-3

weeks)
3. The application: treatment and urgent
prophylaxis
4. The agents:
Ab: antitoxin, antiserum,
human gammaglobulin, synthetic peptides

Artificial active
`
immunization
immunization
Injecting
agents: Ag (vaccines, toxids)
Producting
time: slow
(induction phase:1-4W)
Persistenting
time: long (months or years)
The main
application: specific prophylaxis
(infectious diseases)

Artificial passive

Ab (antitoxin,
antiserum)
at once
slow (2weeks or
months)
urgent prophylaxis
or treatment

3. Biological product and their application

Biological product
a. Vaccine: Live vaccine (attenuated vaccine)
Killed vaccine
Live vaccine
Chemical vaccine or subunit vaccine
Compound vaccine
Genetic engineering vaccine
Anti-idiotype vaccine
b. Toxoid

Immunotherapy
Conception
1. Immunopotentiator
2. Immunosuppressant
(Immunomodulator)

1. Immunopotentiator and indication

a. Immunopotentiator:
- Chemical agents:
levomisole, cimetidine, isoprinosine (ISO)
- Microbiological agents: BCG,
- Proteins of immune system: Ig,

b. Indication:
e.g. Tumor, Immunodeficiency, Infectious
diseases

2. Immunosuppressant and indication

a. Immunosuppressant:
- Chemical agents: Cyclophosphamide, Azathioprine
- Hormone: steroids
- Microbiological agents: CyclosporineA (CsA),
Tacrolimus, FK-506
b. Indication:
- Organ transplantation
- Hypersensitivity diseases
- Autoimmune diseases

Immunosuppression with Drugs

Cyclosporin

Azathioprine

Tc

IL-2

IFN

IL-2R

Steroids

Th
CD4

CD8

Tc

proliferation

TCR-CD3
TCR-CD3

MHC-II

MHC-I

APC

Graft cells

Tc

Hypersensitivity Disease,
Autoimmunity Disease
Graft rejection responses
Ag

APC

MHC

TCR

TH
inactivation

B7
CD28

Anti-B7Ab
CTLA4 Ig
Anti-CD28

co-stimulatory signals

3. Immunomodulator and the use of them

a. Biological response modifier, BRM
b. Classification and function of BRM

Classification and function of BRM

1. Immunoreconstitution:
haemopoietic stem cell and thymus
2. Monoclonal antibodies (McAb) and targeted drug
McAb: Anti-CD3, Anti-CD4, Anti-CD8
Targeted drug: Immunotoxin, IT
Immunoconjugate,
Radioimmunoconjugate
3. Cytokines and activated immune cells
Cytokines : ILs, IFN, TNF, CSF, TGF and Small
molecular polypeptides.
immune cells: LAK, T cell
4. Tumor vaccine
5. Gene therapy

McAb-toxin

McAb-medicine

Tumor

McAb-isotope
McAb-enzyme

Cytokine therapy for tumors

Cytokine

tumor type and results

IFN

Prolonged remissions of
hairy-cell leukemia
weak effects on some
carcinoma

IFN

remission of peritoneal
carcinoma of the ovary

IL-2

TNF

Cytokine effects and possible

anti-tumor mechanisms
possible cytostatic
effect on tumor
increased expression of
MHC class I, cytostasis

increased MHC class I and II

macrophage activation
Tc activation, cytostasis
Remission in renal cancer T-cell activation and
and melanoma
proliferation
NK-cell activation
? Increased tumor cell adhesion
can reduce
macrophage and lymphocyte
malignant ascites
activation

Enhancing immune response: Tumor immunity treatment

Ag

Tumor cell

MHC

TCR

CTL
Signal 1
signal2

CTLactivated
Killer tumor cell

CD28

Ag

Tumor cell

MHC

TCR

CTL
Signal 1
signal2

B7
CD28

TransfectionB7gene

CTLactivated
Killer tumor cell