GIRIJANANDA CHOWDHURY UNIVERSITY

PRESENTATION ON
IMMUNOSTIMULANTS & IMMUNOSUPPRESSANTS

PRESENTED BY

SUBHAM SINGH
M.PHARM, PHARMACOLOGY(2023-25)
SCHOOL OF PHARMACEUTICAL SCIENCE, GCU, AZARA
 CONTENTS
•WHAT IS IMMUNITY?
•TYPES OF IMMUNITY
•IMMUNOSUPPRESSANTS
•T-CELL REGULATION MOA
•IMMUNOSUPPRESSANT DRUGS
•IMMUNOSTIMULANTS
•CLASSIFICATION
•DIFFERENT TYPES OF IMMUNOSTIMULANTS
•REFERENCE
 WHAT IS IMMUNITY?

• Immunity refers to the body's ability to resist or fight off infection

and disease.

• It involves a complex system of cells, tissues, and organs that work

together to defend the body against harmful pathogens such as
bacteria, viruses, fungi, and parasites
 TYPES OF IMMUNITY
. Innate Immunity:

• Innate immunity is the body's first line of defense against pathogens.

• It provides immediate, non-specific protection against a wide range of pathogens.
• Components of innate immunity include physical barriers (like the skin), chemical barriers (like stomach
acid), and cellular defenses (such as macrophages and natural killer cells).
• Innate immunity does not adapt or change with repeated exposure to pathogens.

. Adaptive Immunity:

• Adaptive immunity is a more specialized and targeted immune response that develops over time.
• It is characterized by the production of highly specific antibodies and the activation of T cells that target
specific pathogens.
• Adaptive immunity "remembers" past exposures to pathogens, leading to a quicker and more effective
response upon re-exposure.
• Adaptive immunity is primarily mediated by lymphocytes, including B cells and T cells.
• This type of immunity is the basis for vaccinations, which stimulate the immune system to produce
memory cells for long-term protection against specific diseases.
 IMMUNOSUPPRESSANTS

• Immunosuppressants are medications that suppress or dampen

the activity of the immune system.

• They are commonly used to prevent the body from rejecting

transplanted organs and to treat autoimmune diseases where
the immune system mistakenly attacks the body's own tissues.
T-CELL REGULATION MOA
 The regulation mechanism of Helper T cells by macrophages involves several steps:
• Antigen Presentation: Macrophages phagocytize pathogens and process their antigens
internally. They then present these antigens on their cell surface bound to major
histocompatibility complex (MHC) class II molecules.

• Recognition by Helper T Cells: When a Helper T cell encounters an antigen presented by a

macrophage, its T cell receptor (TCR) binds specifically to the antigen-MHC complex on the
surface of the macrophage.

• Co-stimulation: In addition to TCR recognition, co-stimulatory molecules on the surface of the

macrophage, such as CD80 and CD86, bind to corresponding receptors on the Helper T cell,
providing additional signals necessary for full activation.

• Activation: The binding of the TCR to the antigen-MHC complex and the interaction between
co-stimulatory molecules on the macrophage and the Helper T cell leads to the activation of the
Helper T cell.

• Cytokine Release: Upon activation, the Helper T cell releases cytokines, such as interleukin-2
(IL-2) and interferon-gamma (IFN-γ), which further stimulate the immune response. These
cytokines help in the activation and differentiation of other immune cells, such as B cells,
cytotoxic T cells, and macrophages, leading to a coordinated and amplified immune response
against the invading pathogen.
 IMMUNOSUPPRESSANT
DRUGS

• CALCINEURIN INHIBITORS
• CO-STIMULATORY RECEPTOR BLOCKERS/INHIBITORS
• mTOR INHIBITORS
• ANTI PROLIFERATIVE DRUGS/ ANTI METABOLITES
• CORTICOSTEROIDS
• ANTIBODIES
 CALCINEURIN INHIBITORS

• Calcineurin inhibitors, such as cyclosporin and tacrolimus, bind to

specific proteins within T cells known as cyclophilins & FKBP
respectively.

• This complex inhibits the activity of calcineurin, a phosphatase enzyme

crucial for T cell activation.

• By blocking calcineurin activity, these inhibitors prevent the

production of cytokines like interleukin-2 (IL-2), suppressing T cell
proliferation and immune responses.
 CO-STIMULATORY RECEPTOR
INHIBITORS/BLOCKERS

• Co-stimulatory receptor blockers/inhibitors, such as Abatacept or Belatacept

interfere with the interaction between co-stimulatory molecules on antigen-presenting
cells (APCs) and T cells.

• By blocking co-stimulatory signals, these inhibitors prevent the full activation of T

cells, thereby dampening the immune response.

• This mechanism helps to suppress excessive or inappropriate immune activation,

making co-stimulatory receptor blockers/inhibitors valuable in the treatment of
autoimmune diseases and preventing transplant rejection.
 mTOR INHIBITORS

• mTOR inhibitors, such as sirolimus (rapamycin) and everolimus, bind

to the intracellular protein FKBP12.

• This complex then binds to and inhibits the activity of the mammalian
target of rapamycin (mTOR) kinase, a key regulator of cell growth,
proliferation, and survival.

• Inhibition of mTOR signaling pathway suppresses the proliferation and

function of T cells, leading to immunosuppression and prevention of
graft rejection in organ transplantation.
 ANTI METABOLITES

• Anti-metabolites interfere with the synthesis of DNA and RNA in rapidly dividing cells, including
activated lymphocytes.

• They act by mimicking normal cellular metabolites, which are essential for nucleic acid synthesis,
and competitively inhibit key enzymes involved in these processes.

• By disrupting nucleic acid synthesis, anti-metabolites suppress the proliferation of immune cells,
particularly lymphocytes, thereby exerting immunosuppressive effects.

Eg. Azathioprine (purine)

Mycophenolate Mofetil. (Inosine Monophosphate dehydrogenase inhibitor)

 CORTICOSTEROIDS

• They inhibit NUCLEAR FACTOR OF ACTIVATED T-CELL

(NFAT) and inhibit cytokine production.

• Eg- METHYLPREDNISOLONE, PREDNISOLONE

 ANTIBODIES

• Eg- BASILIXIMAB & DECLIZUMAB (IL2 receptor antagonist).

• Eg- ANAKINRA ( IL1 receptor antagonist).
• Eg- ANTITHYMOCYTE GLOBULIN.
 IMMUNOSTIMULANTS
• An immunostimulant is a substance or agent that enhances the activity or function of
the immune system.

• It works by boosting the body's natural defense mechanisms against pathogens, such as
bacteria, viruses, and other harmful microorganisms.

• Immunostimulants can include various compounds, such as vitamins, minerals, herbal

extracts, peptides, and synthetic molecules.

• They can stimulate different aspects of the immune response, including the production
of antibodies, activation of immune cells like T cells and macrophages, and
enhancement of cytokine production.
 CLASSIFICATION
SPECIFIC IMMUNOSTIMULANTS:

• Specific immunostimulants target particular pathogens or antigens.

• Examples include vaccines, monoclonal antibodies, and interferons.
• They induce a targeted and adaptive immune response, providing protection against
specific infections and promoting immunological memory.

NON SPECIFIC IMMUNOSTIMULANTS:

• Nonspecific immunostimulants activate the innate immune system without targeting

specific pathogens.
• They include compounds like beta-glucans, which enhance the activity of innate immune
cells such as macrophages and neutrophils.
• Nonspecific immunostimulants can improve overall immune function and enhance the
body's ability to respond to a wide range of pathogens.
 DIFFERENT TYPES OF
IMMUNOSTIMULANTS

• BACTERIAL VACCINE
• COLONY STIMULATING FACTORS
• INTERFERONS
• INTERLEUKINS
• THERAPEUTIC VACCINES
• VACCINE COMBINATIONS
• VIRAL VACCINES
 BACTERIAL VACCINES

• Bacterial vaccines contain killed or attenuated bacteria that activate the immune system.
Antibodies are built against that particular bacteria, and prevents bacterial infection later. An example
of a bacterial vaccine is the Tuberculosis vaccine.

• Bacterial vaccines can act as immunostimulants by inducing a specific immune response against
bacterial pathogens. When administered, bacterial vaccines trigger the production of antibodies and
the activation of immune cells, such as T cells and B cells, against the targeted bacteria.

• This immune response helps the body recognize and effectively combat bacterial infections upon
subsequent exposure to the pathogen. By enhancing the body's ability to mount an immune response
against specific bacterial pathogens, bacterial vaccines serve as potent immunostimulants,
contributing to overall immune system function and protection against infectious diseases.
 COLONY STIMULATING FACTORS

Colony-stimulating factors (CSFs) are proteins that regulate the production,

differentiation, and function of white blood cells (WBCs) in the bone marrow.

• They include granulocyte colony-stimulating factor (G-CSF), granulocyte-

macrophage colony-stimulating factor (GM-CSF), and macrophage colony-
stimulating factor (M-CSF).

• CSFs stimulate the growth and differentiation of specific types of WBCs, such as
granulocytes (neutrophils, eosinophils, and basophils), monocytes, and
macrophages.

• CSFs are used therapeutically to boost WBC production in patients undergoing

chemotherapy, bone marrow transplantation, or those with certain immune
disorders.
 INTERFERONS
.

Activation of Immune Cells: Interferons, including interferon-gamma (IFN-γ), play

a key role in activating immune cells such as macrophages, natural killer (NK) cells,
and T cells. Activation of these immune cells enhances their ability to recognize and
eliminate infected or abnormal cells, thereby bolstering the immune response against
pathogens and tumors.

Induction of Immunomodulatory molecules: Interferons stimulate the production

of various immunomodulatory molecules, such as cytokines and chemokines, which
help to regulate immune responses. These molecules can modulate the activity of
immune cells, promote inflammation, and recruit immune cells to sites of infection or
inflammation, thereby enhancing the overall immune response.
 INTERLEUKINS

Interleukins are proteins (Cytokines) that serve as signaling molecules in the

immune system, facilitating communication between different immune cells.

• Activation and Differentiation: Some interleukins, such as interleukin-2 (IL-2) and

interleukin-12 (IL-12), promote the activation and differentiation of immune cells.
For example, IL-2 stimulates the proliferation of T cells, while IL-12 stimulates the
differentiation of T cells.
 THERAPEUTIC VACCINES

• Therapeutic vaccines are a type of vaccine designed to treat or manage existing

diseases rather than prevent them.

• Unlike traditional vaccines, which are administered to prevent infections by

priming the immune system to recognize and respond to specific pathogens,
therapeutic vaccines are used to stimulate the immune system to target and
eliminate disease-causing agents already present in the body.

• Therapeutic vaccines work by training the immune system to recognize and

attack specific antigens associated with diseases such as cancer, infectious
diseases, or autoimmune disorders.
e.g Cancer Vaccines:
• Sipuleucel-T (Provenge)
 VACCINE COMBINATIONS
• Vaccine combinations, also known as combination vaccines, refer to
vaccines that contain multiple antigens or components targeting different
diseases or strains within a single formulation.
• These combinations offer several advantages, including reducing the
number of injections needed, improving vaccine coverage rates, and
streamlining vaccination schedules.
• Here are some examples of vaccine combinations:
Diphtheria, Tetanus, and Pertussis (DTaP) Vaccine.
 VIRAL VACCINES
• Viral vaccines are vaccines designed to prevent viral infections by
stimulating the immune system to recognize and mount a protective
response against specific viruses.
• These vaccines can be made from live, attenuated viruses; inactivated
viruses; viral proteins; or viral genetic material.
• Here are some examples of viral vaccines:
Measles, Mumps, and Rubella (MMR) Vaccine.
 REFERENCE
•Patchen M.L,D'Alessandro MM, Glucan IB , Mechanisms involved
in its radioprotective effect J. Leuk Biol. 19 87:42.95-105.

•Sharma KH, Sharma K.K. Principals of Pharmacology . 1st ed.

Paras Medical Publishers , New Delhi; 2007:428 -453.

•http://en.wikipedia.org/wiki/Immunosuppression.
•http://www.ncbi.nlm.nih.gov/pubmed/10878286
•Lippincott’s illustrated reviews, 5th ed.
•Rang and dale’s pharmacology ,7th ed.
THANK YOU!