11.IMMUNOSUPPRESSANTS

BYBY
Dr.Dr. SAMINATHAN KAYAROHANAMSAMINATHAN KAYAROHANAM
M.PHARM, M.B.A, PhDM.PHARM, M.B.A, PhD
IMMUNOSUPPRESSANTS
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NUM CONTENT SLIDE
1 INTRODUCTION TO IMMUNITY 4,5
2 TYPES OF IMMUNITY 6-11
3 WHAT IS ANTIGENA AND ANTIBODY 12
4 TYPE OF ANTIGENS 13
5 TYPE OF ANTIBODY 14
6 ANTIBODY TARGETS AND FUNCTIONS 15
7 ANTIGEN AND ANTIBODY ACTION/REACTION 16,17
8 NON SPECIFIC DEFENSES 18,19
9 CELLS AND MOLECULES OF IMMUNE RESPONSE 20-22
10 INTRODUCTION TO IMMUNOSUPPRESSANT 23
11 CLASSIFICATION OF IMMUNOSUPPRESSANTS 25
12 ORGAN TRANSPLANT REJECTION 26
13 MECHANISM OF CYCLOSPORINE AND TACROLIMUS 28
14 MECHANISM OF SIROLIMUS AND TACROLIMUS 30
15 MECHANISM OF MYCOPHENOLATE 31
16 ACTION OF IMMUNOSUPPRESSANTS 32
17 SIDE EFFECTS IMMUNOSUPPRESSANTS 33

LEARNING OUTCOME
1. Able to understand the immunity and different types of
immunity.
2. Able to demonstrate the antigen, antibody and
different types of antibody.
3. Able to understand the immunosuppressant and the
diseases treated with immunosuppressant drugs .
4. Able to list the immunosuppressant drugs
classification.
5. Abele to demonstrate the mechanism of
immunosuppressant drugs.
6. Describe the toxic effects of immunosuppressant drugs .

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1. INTRODUCTION TO IMMUNITY
Immunity is the resistance of an organism to infection or
disease.
Immunity is the state of sufficient biological defences to
avoid infection, disease, or other unwanted biological
invasion.”
In biology, immunity is the state of having sufficient
biological defences to avoid infection, disease, or other
unwanted biological invasion. It is the capability of the
body to resist harmful microbesfrom entering it.
Con…
Dr.K.Saminathan.M.Pharm, M.B.A, Ph.D

5

2. TYPES OF IMMUNITY
Con…
A B
6

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 Innate immunity is non- specific. It is first lines of defence.
They defences include secretion of chemical signals, phagocytic
activity, antimicrobial substance and fever.
Examples
Neutrophils,Eosinophils,Mast cells, Monocytes,
Macrophages, Killer cell, Platelets
 Innate immunity also comes in a protein chemical form, called
innate humoral immunity. If an antigen gets past these barriers,
it is attacked and destroyed by other parts of the immune
system.
Examples
Cough reflex, Enzymes in tears and skin oils, Mucus (which
traps bacteria and small particles),Skin, Stomach acid
2. A. INNATE IMMUNITY
Con…

8
FIRST LINE OF DEFENCE – NON-SPECIFIC BARRIERS

9
2.B. TYPE OF ACQUIRED IMMUNITY
Con…

10
Con…
2.B. TYPE OF ACQUIRED IMMUNITY

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PRODUCTION OF MONOCLONAL ANTIBODIES BY
THE HYBRIDOMA METHOD

12
An antigen may be a foreign substance from the
environment such as chemicals, bacteria, viruses, or
pollen. An antigen may also be formed within the body,
as with bacterial toxins or tissue cells. An antigen is any
substance that causes your immune system to produce
antibodies against it.
An antibody (Ab), also known as
an immunoglobulin (Ig), is a large Y-shape protein
produced by B cells that is used by the immune system
to identify and neutralize foreign objects such as
bacteria and viruses. The antibody recognizes a unique
part of the foreign target, called anantigen.
3. WHAT IS ANTIGENA AND ANTIBODY?

1.Exogenous antigens
Exogenous antigens are antigens that have entered the body from the outside,
for example by inhalation, ingestion, or injection.
2.Endogenous antigens
Endogenous antigens are antigens that have been generated within previously
normal cells as a result of normal cell metabolism, or because of viral or
intracellular bacterial infection.
3.Autoantigens
An autoantigen is usually a normal protein or complex of proteins (and
sometimes DNA or RNA) that is recognized by the immune system of patients
suffering from a specific autoimmune disease.
4.Tumour antigens or neoantigens
Those antigens that are presented by MHC I or MHC II molecules on the
surface of tumor cells. These antigens can sometimes be presented by tumor
cells and never by the normal ones. In this case, they are called
tumor-specific antigens (TSAs) and, in general, result from a tumor-specific
mutation.
4. TYPE OF ANTIGENS
13

5. TYPE OF ANTIBODY
14

15
6. ANTIBODY TARGETS AND FUNCTIONS
15 Dr.K.Saminathan.M.Pharm, M.B.A, Ph.D

7. ANTIGEN AND ANTIBODY ACTION/REACTION
Con…
16

7. ANTIGEN AND ANTIBODY ACTION/REACTION
Con…
17

8. NON SPECIFIC DEFENSES
Con…
18

8. NON SPECIFIC DEFENSES
19

9. CELLS AND MOLECULES OF IMMUNE RESPONSE
Con…
20

Con…
21

22

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Immunosuppressant drugs are a class of drugs that suppress or reduce
the strength of the body’s immune system. They are also called anti-
rejection drugs. One of the primary uses of immunosuppressant drugs is
to lower the body’s ability to reject a transplanted organ, such as a liver,
heart or kidney.
Almost everyone who receives an organ transplant has to take
immunosuppressant drugs. The body recognizes a transplanted organ as
a foreign mass. This triggers a response by the body’s immune system to
attack it.
By weakening the immune system, immunosuppressant drugs
decrease the body’s reaction to the foreign organ. The drugs allow the
transplanted organ to remain healthy and free from damage
10. INTRODUCTION TO IMMUNOSUPPRESSANT

24
Immunosuppressant drugs also are used to treat autoimmune
diseases such as lupus. An autoimmune disorder is a disease
process in which the body attacks its own tissue. Lupus results
from just such a misdirected activity of the body’s own immune
system. By suppressing this reaction, immunosuppressant
drugs can help control the impact of the disease on the body.
OTHER DISEASES TREATED WITH IMMUNOSUPPRESSANT DRUGS INCLUDE:
•Psoriasis
•Rheumatoid arthritis
•Crohn’s disease, a chronic inflammation of the digestive tract
•Multiple sclerosis
•Alopecia areata (patchy hair loss)

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11. CLASSIFICATION OF
IMMUNOSUPPRESSANTS

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1. ABO-incompatible transplants
2 Immunologic mechanisms of rejection
•2.1 Immunization
•2.2 Immune memory
•2.3 Cellular immunity
•2.4 Humoral immunity
o2.4.1 Antibody
o2.4.2 Opsonization
o2.4.3 Complement cascade
3 Medical categories of rejection
•3.1 Hyperacute rejection
•3.2 Acute rejection
•3.3 Chronic rejection
4 Rejection due to non-adherence
12. ORGAN TRANSPLANT REJECTION
Con…

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12.ORGAN TRANSPLANT REJECTION

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13. MECHANISM OF CYCLOSPORINE AND TACROLIMUS
Il-2 = interleukin-2; mTOR = mammalian target of rapamycin;
NFATc = cytosolic nuclear factor of activated T cells Con…

29
Cyclosporine preferentially suppresses cell-mediated immune
reactions
After diffusing into the T cell, Cyclosporine binds to a
cyclophilin (more generally called an immunophilin) to form a
complex that binds to calcineurin.
The latter is responsible for dephosphorylating NFATc
(cytosolic Nuclear Factor of Activated T cells).
The CsA-calcineurin complex cannot perform this reaction;
thus, NFATc cannot enter the nucleus to promote the reactions
that are required for the synthesis of a number of cytokines,
including IL-2.
The end result is a decrease in IL-2 the primary chemical
stimulus for increasing the number of T lymphocytes.

30+
14. MECHANISM OF SIROLIMUS AND TACROLIMUS
SIROLIMUS AND TACROLIMUS bind to
the same cytoplasmic FK-binding protein,
but instead of forming a complex with
calcineurin, SRL binds to molecular
target of rapamycin interfering with
Signal.
The latter is a serine-threoninekinase
Binding of SIROLIMUS to molecular
target of rapamycin blocks the
progression of activated T cells from the
G1 to the S phase of the cell cycle and,
consequently, the proliferation of these
cells.
Unlike Cyclosporine and Sirolimus and
Tacrolimus does not owe its effect to
lowering IL-2 production but, rather, to
inhibiting the cellular responses to IL-2.

31
Mycophenolate safety and efficacy in
prolonging graft survival.
It has been successfully used in heart,
kidney, and liver transplants.
As an ester, it is rapidly hydrolyzed in the
gastrointestinal tract to mycophenolic
acid (MPA), which is a potent, reversible,
uncompetitive inhibitor of inosine
monophosphate dehydrogenase,
blocking the de novo formation of
guanosine phosphate.
Thus, like 6-MP, it deprives the rapidly
proliferating T and B cells of a key
component of nucleic acids.
15. MECHANISM OF MYCOPHENOLATE

32
16.ACTION OF IMMUNOSUPPRESSANTS

33
•Nausea, vomiting, diarrhea, or stomach ulcers.
•Rash.
•General feeling of being ill (malaise).
•Liver inflammation.
Rare side effects include:
•Suppression of blood cell production (bone marrow
suppression), which may increase the risk of infection
or serious bleeding. Return to normal blood cell
production may take several weeks after the medicine
is stopped.
•Fever
•Inflammation of the pancreas (pancreatitis)
17. SIDE EFFECTS IMMUNOSUPPRESSANTS

11.IMMUNOSUPPRESSANTS

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