Immunopharmacology

1. IMMUNOPHARMACOLOGY
Ma. Janetth B. Serrano, M.D., DPBA

2. IMMUNOPHARMACOLOGY
•2 major components of the
immune system:
•INNATE
 Physical – skin, mucus membrane
 Biochemical – complement, lyzosyme
 Cellular – macrophages, neutrophils
•ADAPTIVE
 Antibodies – HUMORAL immunity
 T-lymphocyte – CELL MEDIATED
immunity

3. COMPLEMENTS in Innate Immunity:
1. C3a, C5a  chemotaxis
2. C3b  opsonization
3. C5b, C6, C7, C8, C9  MAC
IMMUNOPHARMACOLOGY

4. IMMUNOPHARMACOLOGY
0psonized
bacteria Macrophage
APC
T lymphocyte
IL-2 IL-2
IFN-g
Activated
Macrophage
Activated
NK cells
Activated
Cytotoxic T
cell
CELL-MEDIATED IMMUNITY
B lymphocyte
IL-4,IL-5
TH
1
TH
2
Memory
B Cells
Plasma Cells:
-IgG - IgM
- IgA - IgD
HUMORAL IMMUNITY
IFN-g
TNF-b
IFN-g

5. T-helper cells:
1. TH1 subset
- IFN- g, IL-2, TNF-b
2. TH2 subset
- IL-4, IL-5, IL-6, IL-10
IMMUNOPHARMACOLOGY

6. ABNORMAL IMMUNE RESPONSES:

HYPERSENSITIVITY
 AUTOIMMUNITY
 IMMUNODEFICIENCY
IMMUNOPHARMACOLOGY

7. 1. Corticosteroids
2. Cyclosporine
3. Sirolimus
4. Tacrolimus
5. Interferons
6. TNF-alpha binding drugs
7. Mycophenolate mofetil
8. 15-Deoxyspergualin
9. Thalidomide
10. Glatiramer
IMMUNOPHARMACOLOGY
Immunosuppressants

8. IMMUNOPHARMACOLOGY
Corticosteroids
•MOA:
•inhibit T-cell proliferation & T-cell
dependent immunity
•Inhibit expression of genes
encoding cytokines
•Inhibit production of inflammatory
mediators
•Affects cell-mediated immunity
more than humoral immunity

9. •Continuous administration:
•↑ fractional catabolic rate of IgG
•Indications:
•Autoimmune disorders
- autoimmune hemolytic anemia, LE
- ITP, Inflammatory Bowel Dse,, Hashimoto’s
•Modulate allergic reactions - asthma
•Organ transplantation – rejection crisis
IMMUNOPHARMACOLOGY
Corticosteroids

10. •Immunosuppressive dose:
 10-100 mg/day
•Adverse effects:
 GI bleeding
 adrenal suppression
 fluid retention
 diabetes
 proximal muscle wasting
 superinfections
IMMUNOPHARMACOLOGY
Corticosteroids

11. •Blocks T-cell activation
•binds to cyclophillin  inhibits calcineurin
activity  inhibits gene transcription of
IL-2, IL-3, IFNg & other factors
•Most commonly used immunosuppresant for
renal transplantation
•Indications:
transplant rejection (kidney, liver, pancreas,
cardiac)
Autoimmune disorders (uveitis, RA, DM type1)
•Toxicities:
nephrotoxicity, hyperglycemia, hyperlipidemia,
osteoporosis, hair growth, transient liver
↑
dysfunction
IMMUNOPHARMACOLOGY
Cyclosporin

12. Tacrolimus
•Binds to FK-binding protein 
inhibits T-cell activation
•10-100 times more potent than
cyclosporine
•Liver & kidney transplant
•Oral or IV : t½ = 9-12 hrs
•Toxicity:
nephrotoxicity, neurotoxicity,
hyperglycemia, GI dysfunction
IMMUNOPHARMACOLOGY

13. •Binds also to immunophyllin 
blocks the response of T-cell to
cytokines
•Potent inhibitor of B-cell
proliferation & Ig production
•Indications:
•Kidney & heart allografts
•C syclosporin  psoriasis &
uveoretinitis
IMMUNOPHARMACOLOGY
Sirolimus (rapamycin)

14. •Type 1: induced by viral inf.
•IFN-alpha  prod. by leukocytes
•IFN-beta  fibroblasts & epithelial cells
•Type 2: IFN-gamma  produced by
activated T-lymphocytes
•Indications: cancer
•IFN-b  multiple sclerosis
•IFN-g chronic granulomatous disease
IMMUNOPHARMACOLOGY
Interferons

15. •INFLIXIMAB
•Chimeric IgG1 monoclonal antibody
with human region & murine regions
•Suppress generation of cytokines
•Crohn’s disease; RA
•ETANERCEPT
•Chimeric protein with human regiom
•Similar MOA with infliximab but
shorter half-life
•RA
IMMUNOPHARMACOLOGY
TNF-α binding
drugs

16. •Inhibits a series of T & B lymphocyte
responses
•Inhibit de novo pathway of purine
synthesis
•Renal & heart transplantation
•Mizoribine – inh. nucleotide synthesis
PW; kidney transplants
•Brequinar Sodium – inh. de novo
pathway of pyrimidine synthesi; cancer
& organ transplantation
IMMUNOPHARMACOLOGY
Mycophenolate Mofetil

17. •Potent antimonocytic &
antilymphocytic effect
•Inhibits T & B lymphocyte
response
•Renal transplants; pancreas &
heart transplants
IMMUNOPHARMACOLOGY
15-Deoxyspergualin

18. •Sedative drug
•Favors TH2 over TH1
•Suppress TNF-α production
•Antiangiogenesis action:
teratogenicity & anticancer
•Indications
•Erythema nodosum leprosum (skin
manifestations of SLE)
•Lung transplantation
IMMUNOPHARMACOLOGY
Thalidomide

19. •Relapsing-remitting form of
multiple sclerosis
•Subcutaneous injection
•Toxicities:
•Transient post-injection reaction
IMMUNOPHARMACOLOGY
Glatiramer

20. IMMUNOPHARMACOLOGY
CYTOTOXIC Agents:
1. Azathioprine
2. Leflunomide
3. Cyclophosphamide

21. •Metabolized to 6-mercaptopurines
•Inhibit purine synthesis interferes
with nucleic acid metabolism  inhibits
cellular & humoral responses
•Highly teratogenic
•Well absorbed from GI tract
IMMUNOPHARMACOLOGY
Azathioprine

22. •Renal allograft, AGN, SLE(renal), RA,
Crohn’s disease
•Prednisone-resistant antibody-mediated
ITP
•Autoimmune hemolytic anemia
•Toxicities:
•Bone marrow suppression
•GI disturbances: N&V, diarrhea
•Skin rashes, drug fever, hepatic dysfunction
IMMUNOPHARMACOLOGY
Azathioprine

23. •Prodrug of an inhibitor of pyrimidine
synthesis
•Inhibits lymphoid cells
•Orally active
•RA
•Toxicities:
•Headache, nausea & diarrhea
•Hepatic dysfunction, renal impairment
•Teratogenic
IMMUNOPHARMACOLOGY
Leflunomide

24. •Most potent immunosuppressive drug
•Destroys proliferating lymphoid cells
•Autoimmune disorders: SLE
•Acquired factor XIII antibodies
•Bleeding syndromes
•Toxicities:
•Pancytopenia, hemorrhagic cystitis
IMMUNOPHARMACOLOGY
Cyclophosphamide

25. Antibodies as Immunosuppressive Agents
•Antilymphocytic antibody
•Immune Globulin IV
•Hyperimmune Immunoglobulins
•Monoclonal Antibodies
•Rh
o
(D) Immune Globulin Micro-Dose
Prevention of hemolytic disease of
the newborn
Given to mother within 72 hrs after
delivery of an Rh-negative baby
IMMUNOPHARMACOLOGY

26. 1.Muromonab- CD3
2. Palivizumab
3. Rituxumab
4.Trastuzumab
IMMUNOPHARMACOLOGY
MONOCLONAL ANTIBODIES:

27. •T-cell specific antibody
•Renal transplantation, heart /
renal
IMMUNOPHARMACOLOGY
Muromonab-CD3

28. •Palivizumab – RSV
•Rituximab – follicular B-cell
non-hodgekins lymphma
•Trastuzumab – metastatic
breast CA
IMMUNOPHARMACOLOGY

29. IMMUNOMODULATORS
•CYTOKINES
Interferon-alpha:
- hairy cell leukemia
- chronic myelogenous leukemia
- malignant melanoma
- Kaposi’s sarcoma
- anticancer  renal cell CA,
carcinoid syndrome, T cell leukemia

30. IMMUNOMODULATORS
•CYTOKINES
Melanoma and Prostate cancerGM-CSF
(+) effects in response to Hep B
vaccine
Interferons & IL-2
Malignant melanoma
Soft tissue sarcoma of
extremities
TNF-alpha
Metastatic renal cell CA
Malignant melanoma
Interleukin-2
Chronic granulomatous diseaseInterferon-gamma
Relapsing type multiple
sclerosis
Interferon-beta

31. IMMUNOPHARMACOLOGY
IMMUNOMODULATORS
IMMUNOPHARMACOLOGY
 LEVAMISOLE:
- antiparasitic agent
- potentiate action of fluorouracil
in adjuvant therapy of Dukes
class C colorectal CA
- other uses:
> hodgkin’s lymphoma
> RA

32. IMMUNOPHARMACOLOGY
IMMUNOMODULATORS
IMMUNOPHARMACOLOGY
BCG (Bacille-Camille-Guarin):
- immunization against
tuberculosis
- Adjuvant in intravesical
therapy for SF bladder CA

33. IMMUNOPHARMACOLOGY
IMMUNOMODULATORS
IMMUNOPHARMACOLOGY
HIV:
- Inosiplex
- Diethylcarbamate (DTC)
DiGeorge Syndrome of T cell
deficiency
- give THYMOSIN

34. The winds and
waves are
always on the
side of the
ablest
navigator
“The winds and waves are
always on the side of the
ablest navigator”

35. QUIZ
1.Most common adverse effect of corticosteroids
2.The most potent immunosuppressive agent.
3. Adverse effects of
4. CYCLOPHOSPHAMIDE
5.Given to mothers to prevent ‘hemolytic disease of
the newborn’
Write B if the drug inhibits B lymphocytes & its
responses; T if the drug inhibits T lymphocytes &
its responses; and C if it inhibits both T & B cells:
6. Tacrolimus 9. Azathioprine
7. Leflunamide 10. Cyclophosphamide
8. Cyclosporin