1.Presented by:KINJAN MEHTASem.- VII

2. What is IMMUNITY? The word immunity is derived from theLatin word immunes which means exemptfrom. Immunity is usually defined as a state ofrelative resistance to an infection. Substances capable of stimulating immunemechanism are called as antigens. 3. Components of immune system: Lymphocytes. Cellular immunity. Humoral immunity. Immunoglobulin. Lymph nodes. Spleen. Thymus. 4. Thereare 2 types of immunity: Active immunity. Passive immunity. 5. Theimportant components of immune system include: Granulocytes Complement synthesis and antibody formation Cellular immunity Mucocutaneous barriers 6. NEUTROPHILSare synthesized fromGRANULOCYTES, as the totalgranulocyte count falls below 1000 cells/mm3, the rate of bacterial infectionincreases. The common org. affecting this areE.coli, Pseudomonasaeruginosa, Klebsiella, Pneumonia andstapylococcus aureus. The chances of fungal viral and protozalinfection is also very high. 7. Whenthe defect in this system is there theincrease in infection rate is seen. Such effects usually occur through thechronic treatment with chemotherapeuticagents. 8. Itprovides protection against fungalbacterial, viral and protozal infections. Certain drugs, neoplastic diseases andorgan transplantation proceduresparalyzes cellular immunity. 9. They prohibit pathogenic organisms totake entry into the internal vital organs. However these barriers are damaged by ano. of medical devices, procedures, orchemotherapy. This leads to easy access of pathogens tothe internal organs resulting into infectiousstate. 10. (A) ANTI-HISTAMINIC AGENTS: Histamine- binding lymphocytes haveimmunosuppressive activities. By inhibiting their activation , antihistaminicagents improve cell mediated immuneresponse. 11. IT is the non-narcotic analgesic agent thatrelives pain sensation b inhibitingprostaglandin biosynthesis. This leads to significant improvement inthe functioning of t-lymphocytes. Useful in coccidiomycosis andmycobacterial infections. 12. Chemically it is the complex of inosine andan organic salt. It enhances t-cell proliferation,phagocyotsis and chemo taxis throughunknown mechanism. Initially it was found as an anti-viral agent. 13. ITimproves chemotactic responses andimmune mechanisms in patients withdiseases associated withimmunodeficiency. It probably acts by inducing the release ofc-GMP. 14. Onlytwo lymphokines known as IL-1, IL-2 were found to stimulate the patient immunity. 15. Theseare the polypeptides isolated fromthe epithelial cells of thymus gland. They induce formation of mature T- cellsby unknown mechanism. This are given usually in saline i.m. indoses between 0.5mg/kg and 1.0 mg/kg/day for 2-3 weeks and then reduced to 1-3doses per week. 16. Thisis low molecular weight peptide (m.w. less than 6000 Daltons) isolated from blood leucocytes of the patient with delayed hypersensitivity. it has stimulant effect of cell mediated immunity. it may be used in treatment of immunodeficiency syndrome like chronic mucotaneius candidacies, in treatment of recurrent herpes simplex conditions 17. Various phases of immune responsesinclude: (1) antigen reorganisation and/processing. (2) amplification. (3) antibody formation and (4) immune effectors responses. 18. Depending upon the suppressant andstimulate effects exerted by these drugs onimmune system they are categorized as: (1) IMMUNOSUPPRESSANTS (2) IMMUNO ENHANCERS. 19. Phases of immuneSuppressantsEnhancersresponseAntigen recognisation Corticosteriods.BCG vaccine.and processingCyclophosphamideC. Parvumcytimun TetramisoleAmplification.L- Asparaginase Concanavalin A.Corticosteroids.Tetramisole.Cyclophosphamide.Cytimum.5-fluorouracilAntibody formationCorticosteroids.Lipopolysaccaride.CyclophosphamideTetramisole.Cyclosporin Acytimun 20. Phases of immune Suppressants.enhancers.responseImmune affectorCorticosteroidsC. parvum.response Cylcophosphamide tetramisole Cyclosporin A Cytarabine Cytimun Methotrexate. 21. Duringorgan transplantation, certaincomplex antigens or allograts activate thecytotoxic lymphocytes. Their activationresults to the development of cellularimmunity rejects organ transplants. Immunosuppressive agent beneficialeffects in such condition suppressing thecellular immunity. 22. Mostof these agents are primarily used asanti- neoplastic agents. On the basis of the mechanism of action,immunosuppressant can be classified as: 23. Alkylatingcorticosteroidsantimetabolites agents Antibodies andantibiotics enzymesmiscellaneous agents 24. Examples:Betamethasone ,dexamethasone.triamcinolonePrednisolone, hydrocortisonemethylprednisoloneparamethasone 25. They all possess anti allergic and anti-inflammatory and immunosuppressiveactivities. T- lymphocytes are most susceptible to theaction of corticosteroids resulting intolymphopenia. They also effect humoral immuneresponses by inhibiting antibody synthesis. 26. Adverseeffect: High doses cause Osteoporosis,hyperglycemia, ulcer formation andincreased susceptibility for fungalinfections . DOSE: 2-10 mg/kg per day for few weeks. Adverse effect can be reduced by usigcombination of other cytotoxic agents andlowering the dose. 27. Thiskill components of immune responseof body. They give immunosuppressive action tothe rapidly proliferation cells in the marrowand exert cytotoxic effects to thelymphocytes by alkylating their nucleicacid. EXAMPLES:CYLCOPHOSPHAMIDE,CYTIMUN. 28. CYCLOPHOSPHAMIDE: It is a nitrogen mustard and have broadspectrum of antineoplastic and immunesuppressive activities. More effective suppressor of humoralimmune mechanisms. It exerts cyotoxic action on both T-cells andB-cells. DOSE: 2 mg/kg per day. 29. Usuallyused in combination with corticosteroids in treatment of several autoimmune diseases, including Wegeners granulomatosis. Childhood nephrosis, idiopathic thrombocytopenia purpura and severe rheumatoid arthrititis. 30. CYTIMUM: It is analog of cylophosphamide havingbetter therapeutic index. It is specifically effective against B-cells. 31. Thesedrugs act by exerting cyotoxiceffects on rapidly proliferating cells likethose of bone marrow, myeloidtissues, gonadal tissues and g.i. tract. METHOTREXATE, 6-MERCAPTOPURINE, ANDAZATHIOPRINE are extensively studieddrugs which are more toxic to S-phasewhen DNA synthesis is occurring. 32. AZATHIOPRINE: It is imidazole derivative of 6-mercaptopurine having anti-rheumaticactivity along with cytotoxic effect. It is orally effective and having plasma halflife of about 16 hours. It is the most effective suppressant ofphase-II of immune responses. 33. Xanthine oxidase enzyme converts much ofthe drug in liver and RBC to 6-thiouricacid, thioionisic acid and various othermetabolized. Thioinosic acid competitively inhibit synthesisof inosinic acid. This result in inhibition ofDNA synthesis. thus upon the metabolizedactivation, this suppresses both mediated andhumoral immune responses and depressesantibody proliferative responses. 34. AZATHIOPRINE is used orally in thetreatment of acute glomerunephritis,systemic lupus erythematosus,temporalcranial arteritis. It is also used in management of organtransplantation and delay hypersentizingreactions. DOSE: 2-5 mg/kg per day. 35. METHOTREXATE: It is an orally active folic acid analog having antineoplastic and antipsoratic and mild immunesuppressant activity. It has a plasma half-life 7.2-9.0 hours. It acts by inhibiting folate metabolism and affectsphase-II of immune responses. It is used to treat severe psorasis,dermatomcosotis and rheumatoid arthritis and alsoused in organ transplantation procedure. Other drug include chlorambucil, mercaptopurine,thioguanine, azarbine, cytarabine. 36. CYCLOSPORIN A is he example for thishaving immunosuppressive. It is the cyclicactivity and is isolated from the soil fungus,Tolypolacadofium inflatum. It spefically inhibit generation of effectorsT-lymphocytes without expressing effect ofsuppressor lymphocytes and B-cellsactivity. It impairs proflirative response of T-cellsof antigens. 37. Once T-cells are stimulated by antigensthey synthesized interculin -2 thats startgrowth promoting effects on T-lymphocytes. Cyclosporine has low activity profile. A.E.: gumhypertropy, tremor.Neurasthesia, depressive psychosis andbenign breast tumours. It has plasma half life of 10-27 hours. 38. USEDin organ transplantation in patientshaving liver, kidney, pancreas disorder andheart transplantation. It also expands its effects in the treatmentof immune diseases of rheumatic arthritis. DOSE: adult oral dose is 10-20 mg/kg perday. i.v. 50 mg diluted intranasal saline may begiven by slow infusion. 39. L-ASPARAGINASEis the drug of choicein treatment of acute lymphoblasticleukaemia. It has half life of about 11-23 hours. this enzyme is usually given i.v. or i.m. When combined with methotrexate itlowers down the adverse effect andintensifies its activity. 40. EXAMPLE: ANTITHYMOCYTE GLOBULIN (ATG) ATGis used alone or in combination withazathioprine and corticosteroids in theprevention of the renal allograft rejection inthe dose of 1-5 mg/kg per day. However in some patients , allergicreactions has been reported to occur toleading to serum sickness and nephritis. 41. (A) ADENOSINE DEAMINASEINHIBOTORS; Examples are erythro-9-(2-hydroxy-3-nonyl) adenine hydrochloride and 2-deoxy- coformycin.(pentastatin). Former one have effect on T-lympohcyteswhile pentastatin is used as antimetabolite. 42. (B)BREDININ: It is an imidazole nucleoside havingantimetabolite antineoplastic activity and isused as an immunosuppressant in humankidney transplantation. (C) CYCLOIMMUNE: It is analog of cyclosporine, undergoingclinical trials and showing activity for organtransplantation. 43. (D) NIRIDAZOLE: It is an orally active nitrothiazole derivativehaving anthelmintic activity, anti bacterialand immunosuppressive activities. It is used to suppress cell- mediatedimmunity response. 44. This category of the drugs is used toovercome immunodeficiency orimmunosupreesion arising as a result ofeither inherited or acquired disorders ofimmune system. Examples of inherited disorders:Agammaglobulinemia and Severe combinedimmune deficiency syndrome (SCIDS). Causes: chemotherapy. Radiation or viralinfection may cause immunosupreesion. 45. Examplesof this category include : (a) BCG Vaccine: It is used as immunological enhancer tostimulate intact immune system (i.e. a non-specific immunoenhancer.) of the body. BCG and its methanol extracted residue(MER) contain muramyl dipeptide as anactive immunostimulant ingredient. 46. T-lymphocytes are principle target cells for the actionof BCG vaccine. It causes stimulation of macrophage function,phagocytic activity, lysosomal enzyme activity andchemotaxis mechanisms . It induces the production of lymphocyte-activity factorresulting of phase I of immune response. Because of its activity against tumour antigen it isbeneficial in treatment of lung and breast cancer, acutelympholytic and myelogeneous leukaemia. It is available as unlyophilized, live or killed lyophilizedform. Administration as oral, i.v., i.p., i.d. , intralesional. 47. Levamisole is orally active S(-) isomer oftetramisole. It is used as immunostimulant in thetherapy of certain infections, r.a., andimmunosuppressive conditions It mainly acts by raising c-GMP levels throughinteraction with thymopoietien receptor sites. thisleads to decrease in metabolic inactivation of c-GMP accompanied with increased breakdown of c-AMP. The increase in c-GMP level induceslymphocyte proliferation and augmentation ofchemotactic responses. This reflects into increased antibodyproduction, lymphokine production, increasedphagocytosis. 48. Tetramisoleis used in treatment of: (1)certain chronic and recurrent bacterialinfections (2) certain diseases with immunodeficiencylike chronic granulomatous syndrome,jobs syndrme etc. (3) autoimmune diseases like r.a., crohnsdisease, SLE. 49. OTHERSARE: Corynebacterium parvum Tilorone Inosiplex Lipopolysaccharides Dialyzable leukocyte extract