1. Ma. Janetth B. Serrano, M.D., DPBA
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. IMMUNOPHARMACOLOGY COMPLEMENTS in Innate Immunity:
1. C3a, C5a  chemotaxis
2. C3b  opsonization
3. C5b, C6, C7, C8, C9  MAC

4. IMMUNOPHARMACOLOGY TH1 TH2 0psonized bacteria Macrophage APC
B lymphocyte
T lymphocyte
IL-4,IL-5
IL-2
IL-2
TH1
TH2
IFN-
TNF-
IFN-
IFN-
Plasma Cells:
IgG IgM
IgA - IgD
Activated
Macrophage
Activated
Cytotoxic T cell
Activated
NK cells
Memory B Cells
CELL-MEDIATED IMMUNITY
HUMORAL IMMUNITY

5. IMMUNOPHARMACOLOGY T-helper cells: 1. TH1 subset - IFN- , IL-2, TNF-
- IL-4, IL-5, IL-6, IL-10

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

7. IMMUNOPHARMACOLOGY Immunosuppressants 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

8. Corticosteroids IMMUNOPHARMACOLOGY 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. Corticosteroids IMMUNOPHARMACOLOGY 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

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

11. Cyclosporin IMMUNOPHARMACOLOGY Blocks T-cell activation
binds to cyclophillin  inhibits calcineurin activity  inhibits gene transcription of IL-2, IL-3, IFN & 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

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

13. Sirolimus (rapamycin)
IMMUNOPHARMACOLOGY
Sirolimus (rapamycin)
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

14. Interferons IMMUNOPHARMACOLOGY 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-  multiple sclerosis
IFN- chronic granulomatous disease

15. TNF-α binding drugs IMMUNOPHARMACOLOGY INFLIXIMAB ETANERCEPT
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

16. Mycophenolate Mofetil
IMMUNOPHARMACOLOGY
Mycophenolate Mofetil
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

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

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

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

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

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

22. Azathioprine IMMUNOPHARMACOLOGY
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

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

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

25. Antibodies as Immunosuppressive Agents
IMMUNOPHARMACOLOGY
Antibodies as Immunosuppressive Agents
Antilymphocytic antibody
Immune Globulin IV
Hyperimmune Immunoglobulins
Monoclonal Antibodies
Rho(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

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

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

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

29. IMMUNOMODULATORS Interferon-alpha: - hairy cell leukemia
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 Interferon-beta Interferon-gamma
Relapsing type multiple sclerosis
Interferon-gamma
Chronic granulomatous disease
Interleukin-2
Metastatic renal cell CA Malignant melanoma
TNF-alpha
Malignant melanoma
Soft tissue sarcoma of extremities
Interferons & IL-2
(+) effects in response to Hep B vaccine
GM-CSF
Melanoma and Prostate cancer

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

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

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