11.immunosuppressants

BYBY

Dr. Dr. SAMINATHAN KAYAROHANAMSAMINATHAN KAYAROHANAM

M.PHARM, M.B.A, PhDM.PHARM, M.B.A, PhD

IMMUNOSUPPRESSANTS

11

2

NUM CONTENT SLIDE 1 INTRODUCTION TO IMMUNITY 4,52 TYPES OF IMMUNITY 6-113 WHAT IS ANTIGENA AND ANTIBODY 124 TYPE OF ANTIGENS 135 TYPE OF ANTIBODY 146 ANTIBODY TARGETS AND FUNCTIONS 157 ANTIGEN AND ANTIBODY ACTION/REACTION 16,178 NON SPECIFIC DEFENSES 18,199 CELLS AND MOLECULES OF IMMUNE RESPONSE 20-22

10 INTRODUCTION TO IMMUNOSUPPRESSANT 2311 CLASSIFICATION OF IMMUNOSUPPRESSANTS 25

12 ORGAN TRANSPLANT REJECTION 2613 MECHANISM OF CYCLOSPORINE AND TACROLIMUS 2814 MECHANISM OF SIROLIMUS AND TACROLIMUS 3015 MECHANISM OF MYCOPHENOLATE 3116 ACTION OF IMMUNOSUPPRESSANTS 3217 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 .

4

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

5Dr.K.Saminathan.M.Pharm, M.B.A, Ph.D

2. TYPES OF IMMUNITY

Con…

A B


7

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.

ExamplesCough 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…


10Con…

2.B. TYPE OF ACQUIRED IMMUNITY


11

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 systemto 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 antigensExogenous antigens are antigens that have entered the body from the outside, for example by inhalation, ingestion, or injection.

2.Endogenous antigensEndogenous 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.AutoantigensAn 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 neoantigensThose 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


5. TYPE OF ANTIBODY


15

6. ANTIBODY TARGETS AND FUNCTIONS

1515 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


9. CELLS AND MOLECULES OF IMMUNE RESPONSE

Con…20



Con…21


23

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)


25

11. CLASSIFICATION OF IMMUNOSUPPRESSANTS


26

1. ABO-incompatible transplants2 Immunologic mechanisms of rejection

2.1 Immunization2.2 Immune memory2.3 Cellular immunity2.4 Humoral immunity

o2.4.1 Antibodyo2.4.2 Opsonizationo2.4.3 Complement cascade

3 Medical categories of rejection3.1 Hyperacute rejection3.2 Acute rejection3.3 Chronic rejection

4 Rejection due to non-adherence

12. ORGAN TRANSPLANT REJECTION

Con…


27

12.ORGAN TRANSPLANT REJECTION


28

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

Health & Medicine

immunity immunity

immunity dr

different types of immunity

platelets innate immunity

innate humoral immunity

type of antibody

barriers dr

different types of antibody