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IMMUNE RESPONSE

IMMUNE RESPONSE. The specific reactivity induced in a host by an antigenic stimulus. Antigen. Infectious. Non-infectious. Out come of antigenic stimulus Beneficial response (Immunity) Injurious response ( Hypersensitivity) No response (Tolerance). AMI (Humoral). Immune response.

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IMMUNE RESPONSE

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  1. IMMUNE RESPONSE

  2. The specific reactivity induced in a host by an antigenic stimulus. Antigen Infectious Non-infectious • Out come of antigenic stimulus • Beneficial response (Immunity) • Injurious response (Hypersensitivity) • No response (Tolerance) AMI (Humoral) Immune response CMI (Cell mediated)

  3. Humoral Imm Response Scope: • Defense against external cell pathogens. • Pathogenesis of Type I, II & III Hypersensitivity and some Auto immune diseases.

  4. Primary and secondary Response Primary: Facing antigenic stimulus for first time • Slow sluggish, short lived • A long lag phase • Low titre of antibody. • Do not persist for long. • Antibody, IgM in nature

  5. Secondary response: • Subsequent stimuli with same Ag • Prompt, powerful prolonged. • No or short lag phase • High titer of antibody. • Persist for a long period • Antibody, IgG in nature

  6. Primary response

  7. Secondary Response

  8. Factors influencing Ab Production • Genetic factor • Age, nutritional status • Route of administration • Size and No of doses. • Multiple antigens • Adjuvants • Immuno suppressive agents. • Effect of Ab

  9. Factors Influencing…… Genetic factors: • Different individuals in a single species show difference in immune response to same Ag. • Gene situated in the short arm of 6th chromosome. • Embryo is immunologically immature. Capacity to produce Ab starts after development of lymphoid system.

  10. When potential immuno competent cell comes in contact with specific Ag, during embryonic life, the response is elimination of cells or induction of tolerance. This is believed to the basis of non antigenicity to self Ag. • Imm competence is not complete at birth. Infant has to depend on mother’s Ab till 3-6 months. Full competence is achieved about the age of 4 years.

  11. Nutritional Status: • Malnutrition affects Immune response adversely. Protein caloric malnutrion affects both AMI and CMI. • Deficiency of amino acids and vitamins (A & B group) cause ↓ in Ab production. Route of administration: • Humoral response is better in parentral administration • Large particulate Ag (Bact.,Erythro) more effective iv. Sol Ag effective subcutaneously. • Route of administration may influence type of Ab Oral, Nasal Ig A. • Inhalation (Polen etc.) Ig E, Parentral Ig G Application of chemicals to skin CMI

  12. Size and number of doses: • The antibody to Ag is dose dependent. • Effective only after a minimum dose. • The response is increased if the dose is increased up to a critical level after which will inhibit immune response (Immune Tolerance). Immunological paralysis: • The antigenic stimulus appears to swap Ab producing system and completely paralyse it.

  13. Multiple Antigens • When 2 or more Ags are adminstered the effects vary. Typhoid + Cholera vaccines Not influenced Toxoids + Bact. vaccines Response to toxoid is potentiated • For an optimal effect, the nature and relative proportion of diff. Ags in a mixture should be carefully adjusted.

  14. Adjuvants • Confer immunogenicity to non-antigenic substances • Increase the concentration and persistence of Ab. • Induce and enhances CMI Examples: Al. hydroxide, Al-phosphate, Freund’s incomplete adjuvant (Ag incorporated in water phase, of a water in oil emulsion). Freunds Adjuvants (Incomplete Freund + killed tubercle bacilli)

  15. Immuno Suppressive Agents They inhibit the immune responses. • Irradiation: Sub – lethal whole body irradiation suppresses Ab response. • Radiomimetic drugs: Cyclophosphamide, Nitrogen mustard suppress Ab production. • Corticosteroids: cause depletion of lymphocytes from blood and lymphoid organs. Therapeutic doses have little effect. • Antimetabolites (Methotrexate 6-mercaptopurine inhibit synthesis of DNA & RNA.

  16. Effects of Antibody • The humoral response to an antigen can be suppressed specifically by passive administration of homologous antibody. Eg:- Rh sensitization

  17. AB mediated defense • Clumping followed by phagocytosis • Opsonization followed by phagocytosis • Neutralization • Complement mediated lyses • ADCC Mechanism

  18. Activation of ‘B’ cells • Unlike ‘T’ cells, ‘B’ cells recognize the immunogen in its free and unprocessed form. • Two signals are needed for ‘B’ cell activation • First signal is the specific binding of the antigenic receptor with the membrane bound form of immunoglobin present in the surface of the ‘B’ cells • Second signal provided by the activated helper ‘T’ cells (CD 40 L) binds to protein called CD 40 on ‘B’ cells.

  19. MONOCLONAL ANTIBODIES AND HYBRIDOMA TECHNIQUE

  20. Introduction • Antibodies have many applications in diagnosis, therapy and research. • Until recently antibodies were produced by inoculating Ag into animal and taking serum some time latter. • The draw back with above conventional antisera is that they are a heterogeneous mixture of antibodies of different specificities, affinities and classes. • Sought after Ab might be present in low conc. In the serum. • Conventional antisera may produce unwelcome cross reactions because of heterogenicity.

  21. Definition • Ab produced by a single clone of cells directed against a single antigenic determinant. The antibodies produced by single clone of cells are specific i.e antibody of single class which have high affinity.

  22. Hybridoma Technique • 1975 Method devised by G. Kohler and C. Milestein, Monoclonal antibodies of desired specifically • 1984 In recognition to this Hybridoma Tech. they were awarded Nobel prize. • Principle: Fusion of an antibody producing ‘B’ cell with myeloma cell to producing a hybrid myeloma called Hybriodoma.

  23. Hybriodoma possesses important properties of both of its parent cells. • The ability to produce specific antibody of ‘B’ cells with permanent growth and • High rate of secretion of myeloma cells for indefinite times. • In short a ‘B’ cell can essentially be immortalized by fusion with a myeloma cell

  24. Applications • diagnostic, therapeutic and research applications. • Mabs are being employed in many areas where antisera were formerly used like blood grouping, tissue typing, hormone RIA.

  25. Application Contd. • Pregnancy can be diagnosed 10 days after conception. Mab to chorionic- gonadotrophin can be used to detect chorionic- gonadotrophin in urine. • Rapid diagnosis of Hepatitis, influenza, Herpes streptococcal and Chlamydia infection. • Mabs used to analyze complex biological system (Molecules on the surface)

  26. Application Contd. • Cancer diagnosis and therapy Diag: To isolate specific molecules. Therapy: Carry cytotoxic drugs, immunotoxin directly to tumor surface (magic bullets)

  27. Cell mediated immune response Specific immune response that does not involve antibody. Scope of CMI: • Delayed hypersensitivity • Immunity against obligate and facultative intracellular parasites. • Transplantation immunity. • Immunity against cancer • Pathogenesis of some autoimmune diseases (thyroiditis, encephalitis etc.)

  28. Bacteria: M. tuberculosis, M. leprae Brucella, Listeria etc. Fungi: Histoplasma capsulatum, Coccidioides immitis, Blastomyces dermatitis. Protozoa: Leishmania spp. Trypanosoma spp. Virus: smallpox, measles, mumps etc.

  29. CELLS INVOLVED IN CMI • APC (Macrophage, B cells, dendrocytes etc) • T Helper cells (CD4, Th1 & Th2) • T suppressor cells (CD8 cells) • N.K. cells • Eosinophils.

  30. CD4 Cell mediated CMI Mostly for Exogenous Ag T Lymphocytes that have the CD4 molecules on their surface recognize antigen fragments in association to MHC II mol of APC. These activated ‘T’ cells secrete lymphokines.

  31. Lymphokines serve 2 main functions • Recruit & activate other leucocytes and promote and inflammatory response. • Act as growth and differentiating factors for ‘T’ and ‘B’ cells.

  32. CD8 cell mediated CMI • Mostly for Endogenous Ag (virus, Tumor cells etc). • CD8 cells recognize fragments Ag in association with MHC I molecule on a target cell and cause cell lyses. • Lyses is brought about by liberation of some substances from the granules of CD8 cells.

  33. The granules contain • Perforin (act like C9) • Serene esterase • No of toxic molecules • TNF –α • TNF –β (Lymphotoxin) • Gama – interferon.

  34. Cytokines • Peptide mediators or intracellular messengers. • Regulate immunological, inflammatory and reparative host responses. • Produced by widely distributed cells (lymphocytes, macrophages, platelets, fibroblasts etc) • Have paracrine and autocrine effect on the cells.

  35. Cytokines (Classification) A) Interleukins: IL1 to IL13 IL1, IL10, IL8 -Macrophage IL7 - stromal cells. All others – T & B cells.

  36. B) Colony stimulating factors,(CSF) - Macrophage (M) CSF - Granulocyte (G) CSF - Gran . Macro (GM) CSF C) Tumor Necrosis factor (TNF) - TNF – Alpha – Macro - TNF – Beta – ‘T’ cells.

  37. D) Interferons IFN – Alpha IFN - Beta Lecocyte Antiviral Fibroblast IFN-Gamma-T cells Antiviral Macro Activation NK cell activation E) TGF – B (Trans growth fact) MHC I, MHC II exp. LIF – Leuk inhib fact) – produced by T- cells Act on stromal cells

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