The document discusses various immunomodulators and their roles in the immune system, detailing types of immunity, therapeutic uses, and adverse effects. It highlights the functions of cytokines, immunostimulants, glucocorticoids, calcineurin inhibitors, anti-TNF agents, and other immunomodulating drugs in treating diseases such as cancer, autoimmune disorders, and transplant rejection. Additionally, it explains the mechanisms of action of these agents and their implications for patient care.

1. IMMUNOMODULATORS

3. TYPES OF IMMUNITY

4. Immune System
• Immune System A biochemical complex that
protects the body against Pathogenic organisms,
Foreign bodies and Its own cells that become
cancerous.
• Immunity: Innate, Natural -Complement,
Granulocytes, Monocytes /macrophages, NK
cells, Mast cells, Basophils Adaptive, Learned - B
and T lymphocytes, B: antibodies, T : helper,
cytolytic , suppressor

5. Immune System
The system incorporates the
• Humoral immune response- B Cells- antibodies .
• Cell mediated response, - uses T-cells
• Dysregulation of this system can result into
serious problem.
• Autoimmune diseases
• Allergic reactions including anaphylaxis
• Tissue/organ rejection

6. Immunostimulants:
Immunostimulants:
• Increase the immune responsiveness of
patients who have either selective or
generalized immunodeficiency.
• Used for:
immunodeficiency disorders, chronic infectious
diseases, and cancer

8. Cytokines
• Cytokines Developed by rDNA (recombinant) technology .
• TNF
• Colony Stimulating factors (G-CSF, M-CSF, GM-CSF, etc)
• Interferon (INF): INF- α,β,γ
• Antiviral, anticancer.
• Adverse Effects: flu-like symptoms, fatigue malaise
• Interleukin-2 (IL-2)
• T cell proliferation, T H , NK, LAK cell activation .
• Treatment of malignant melanoma, renal cell carcinoma,
Hodgkin disease .
• Adverse Effects: fever, anorexia .
• Applications in the treatment of viral infections,
autoimmune and neoplastic diseases

9. Interferons
• Interferons: Group of proteins produced by
white blood cells, fibroblasts, or T-cells as part of
an immune response to a viral infection or other
immune trigger.
• Application in treatment of viral infection,
autoimmune and neoplastic diseases.
• Therapeutic uses- Hairy cell leukemia, Malignant
melanoma, Hepatitis B .
• Adverse Reactions :- Flu like symptoms – Fever,
chills, headache, CVS – Hypotension, Arrhythmia,
CNS- Depression, Confusion.

10. INTERLEUKIN
• INTERLEUKIN:- It is a protein that regulates the
activities of white blood cells (leukocytes, often
lymphocytes) that are responsible for immunity.
IL-2 is part of the body's natural response to
microbial infection, and in discriminating
between foreign ("non-self") and "self". IL-2
mediates its effects by binding to IL-2 receptors,
which are expressed by lymphocytes.
• Therapeutic uses: Metastatic renal cell carcinoma

11. Other Immunomodulators
• Levamisol - antihelmenthic drugs BCG as adjuvants and probably
act by activation of macrophages
• Etanercept :- acting as a TNF inhibitor THALIDOMIDE:- Enhanced
T cell production of cytokines IL-2, IFN- 𝝲 . Increases TNF𝝰 in
patients who are HIV seropositive .
• Therapeutic uses: Multiple Myeloma, Adverse effects:- Birth
defect . Contraindicated in women having child bearing potential.
• ISOPRINOSINE ( Methisoprinol ):- Leads the production of
cytokines such as IL-1, IL-2, and IFN- 𝝲, increase proliferation of
lymphocytes in response to mitogenic or antigenic stimuli.
• Therapeutic uses: Herpes simplex infection, Measles viruses,
• Adverse reactions:- Rise in uric acid in serum and urine, Nausea
Aldesleukin : - Aldesleukin is in a class of drugs known as
cytokines, Aldesleukin increases the body ability to fight cancer.

12. Immunization
• Active – Stimulation with an Antigen. antigen
as a whole, killed organism, or a specific
protein or peptide constituent of an organism
• Passive – Preformed antibody
-Nonspecific immunoglobulins.
• Antibody-deficiency disorders .
-Specific immune globulins
• High titers of desired antibody.
• Hepatitis B, Rabies, Tetanus

13. Vaccines
• Suspensions of live, attenuated (weakened) or
killed (inactivated) micro-organisms .
• The weakened form prevents the person from
contracting the disease .
• Also stimulate the production of antigens against
a specific antibody.
• Vaccinations with live bacteria or virus provide
lifelong immunity.
• Vaccinations with killed bacteria or virus provide
partial immunity, and booster shots are needed
periodically.

18. Glucocorticoids
• Glucocorticoids Induce redistribution of
lymphocytes – decrease in peripheral blood
lymphocyte counts .
• Intracellular receptors – regulate gene
transcription.
• Down regulation of IL-1, IL-6.
• Inhibition of T cell proliferation.
• Neutrophils , Monocytes display poor chemotaxis.
• Broad anti-inflammatory effects on multiple
components of cellular immunity

19. USES - Glucocorticoids
• Transplant rejection
• GVH – BM transplantation
• Autoimmune diseases – RA, SLE,
Hematological conditions
• Psoriasis
• Inflammatory Bowel Disease

21. CALCINEURIN INHIBITORS
• Calcineurin (CN) is a protein phosphatase activates the T
cells of the immune system and can be blocked by drugs.
Cyclosporine –
• Bind to the cytosolic protein cyclophilin (an
immunophilin ) of immunocompetent lymphocytes,
especially T-lymphocytes .
• This complex of cyclosporin and cyclophilin inhibits the
phosphatase calcineurin, which under normal
circumstances induces the transcription of interleukin-2 .
• The drug also inhibits lymphokine production and
interleukin release, leading to a reduced function of
effector T-cells.

22. Uses
• Organ transplantation: Kidney, Liver, Heart
• Rheumatoid arthritis, IBD, uveitis
• Psoriasis
• Aplastic anemia
• Skin Conditions- Atopic dermatitis, Alopecia
Areata, Pemphigus vulgaris, Lichen planus,
Pyoderma gangrenosum

24. Tacrolimus
– It binds to the immunophilin FKBP1A , followed
by the binding of the complex to calcineurin and
the inhibition of its phosphatase activity. In this
way, it prevents the cell from transitioning from the
G 0 into G 1 phase of the cell cycle . Tacrolimus is
more potent than ciclosporin and has less
pronounced side-effects.
Uses
- Prophylaxis of solid-organ allograft rejection
–Topical preparation available for use in atopic
dermatitis and psoriasis.

26. Sirolimus (rapamycin)
• Contrary to cyclosporin and tacrolimus , drugs that
affect the first phase of T lymphocyte activation.
• Sirolimus affects the second phase (namely signal
transduction and lymphocyte clonal proliferation ).
• It binds to FKBP1A like tacrolimus , however the
complex does not inhibit calcineurin but another
protein, mTOR (mammalian target of rapamycin ).

27. Sirolimus (rapamycin)
• It indirectly inhibits several T lymphocyte-
specific kinases and phosphatases , hence
preventing their transition from G 1 to S phase
of the cell cycle.
• Sirolimus prevents B cell differentiation into
plasma cells,.
• reducing production of IgM , IgG , and IgA
antibodies.

28. Anti-IL-2 Receptor Antibodies
( Daclizumab and Basiliximab )
• Bind to IL-2 receptor on surface of activated T
cells ---Block IL-2 mediated T-cell activation.
• Uses :Prophylaxis of Acute organ rejection
• Toxicity :Anaphylaxis, Opportunistic Infections

29. Anti-TNF Agents
• Anti-TNF Agents TNF – Cytokine at site of
inflammation Infliximab Etanercept
Adalimumab

30. Infliximab
Uses :
• Rheumatoid arthritis
• Chron’s disease – fistulae
• Psoriasis
• Psoriatic arthritis
• Ankylosing spondylosis .
• Toxicity
• Infusion reaction – fever, urticaria , hypotension,
dyspnoea
• Opportunistic infections – TB, RTI, UTI

31. • Thalidomide – inhibits angiogenesis, reduces
phagocytosis , enhances cell mediated
immunity – Increases levels of IL- 10 . – Used
in multiple myeloma, graft versus host disease
, myelodysplastic syndrome, colon and
prostrate Cancer.
• Mycophenolate Mofetil – mycophenolic acid
– Inhibits inosine monophosphate
dehydrogenase which is a key enzyme in
guanine nucleotide synthesis . – Used in
steroid refractory GVHD, RA, SLE.

32. • Leflunomide – it inhibits pyrimidine synthesis in
actively dividing cells. Antibodies by B cells is
depressed. Used in RA.
• Cyclophosphamide – alkylating agent which
destroys proliferating lymphoid cells. Used in SLE,
autoimmune haemolytic anaemia , multiple
sclerosis, Wegener’s granulomatosis .
• Muromonab CD3 – T cell receptor complex ( blocks
Ag recognition ). – Used in steroid resistant
rejection.
• Daclizumab , Basiliximab – IL-2 receptor (blocks IL-2
mediated T cell activation ). – Used in acute organ
rejection in renal transplant patients.

33. • Azathioprine ( Mercaptopurine ) – interferes
with purine nucleic acid metabolism and
incorporates false nucleotide.
• –Used in Renal allograft, RA, SLE, ITP, Crohn’s
disease, glomerulonephritis