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Chapter 21: Immunoprophylaxis and Immunotherapy. I. Immunoprophylaxis II. Immunotherapy. I. Immunoprophylaxis. Conception 1. The way of acquired specific immunization 2. The classification and characteristics of Artificial immunization
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Chapter 21: Immunoprophylaxis and Immunotherapy I. Immunoprophylaxis II.Immunotherapy
I. Immunoprophylaxis Conception 1. The way of acquired specific immunization 2. The classification and characteristics of Artificial immunization 3. Biological product and their application
1.The way of acquired specific immunization Natural immunization: heredity, non-specific Acquired immunization: acquired, specific Active immunization: natural, artificial Passive immunization: natural, artificial
Type acquired through Active immunization: Natural infection or inapparent infection Artificial infection: vaccine, toxoid, attenuated organisms inactivated organisms purified microbioal macromolecules Passive immunization: Natural maternal antibody Artificial immune serum Immunity can be acquired through active and passive immunization
I. Immunoprophylaxis Conception 1. The way of acquired specific immunization 2. The classification and characteristics of Artificial immunization 3. Biological product and their application
2.The classification and characteristics of Artificial immunization Artificial active immunization: Artificial passive immunization: Comparison:
Artificial active immunization Conception: Features: 1. The production of the effect: slow ( induction phase:1-4weeks ) 2. The persistent time of immunity: long (months-years) 3. The application: specific prophylaxis 4. The agents: Ag: vaccine, toxids
Artificial passive immunization Conception: Features: 1. The production of the effect: fast 2. The persistent time of immunity: short (2-3weeks) 3. The application: treatment and urgent prophylaxis 4. The agents: Ab: antitoxin antiserum human gammaglobulin synthetic peptides anti-idiotype antibodies
Injecting agents: Ag (vaccines, toxids) Ab (antitoxin, antiserum) Producting time: slow (induction phase:1-4W) at once Persistenting time: long (months or years) slow (2weeks or months) The main application: specific prophylaxis urgent prophylaxis or (infectious diseases) treatment Artificial active Artificial passive immunization immunization
I. Immunoprophylaxis Conception 1. The way of acquired specific immunization 2. The classification and characteristics of Artificial immunization 3. Biological product and their application
3.Biological product and their application Biological product a.Vaccine: Live vaccine (attenuated vaccine) Killed vaccine Comparison*: b.Toxoid: TAT, DAT c.New vaccine: Live vaccine Chemical vaccine or subunit vaccine Compound vaccine Genetic engineering vaccine Anti-idiotype vaccine
活疫苗 死疫苗 接种方式: 模拟自然感染途径 皮下注射 (皮内,划痕法) 接种剂量: 较小 较大 接种次数: 多数只需一次 两次或多次 (体内有一定繁殖) (体内不繁殖) 副作用: 反应较小 反应较大 (发热、全身或局部反应) 免疫效果: 较好,持续3-5年或更长 较差,持续数月-1年 疫苗保存: 易失效,冻干4C保存 较易保存,较稳定 死疫苗和活疫苗的比较
Vaccinia promoter DNA from pathogen Ligation Recombinant plasmid Vaccinia virus Plasmid Plasmid infection transfection Animal-cell culture Recombinant vaccinia Recombinant vaccine
antibody antigen Antigen may be protein, carbohydrate, etc. First antibody selected for high affinity for immunizing antigen, made monoclonal Antigenic determinant Mice immunized idiotype1 Anti-idiotype antibodies Raised against idiotype 1 Second antibodies screened for similarity to original antigen Anti- idiotype 1 vaccine like antigen unlike antigen Anti- idiotype 1 Anti-idiotype antibodies as vaccine
II.Immunotherapy Conception 1.Immunopotentiator and indication 2.Immunosuppressant and indication 3. Immunomodulator and the use of them
1.Immunopotentiator and indication a. Immunopotentiator: Chemical agents: levomisole, cimetidine,isoprinosine(ISO) Microbiological agents: BCG, vp Proteins of immune system: Ig,iRNA b. Indication: e.g. Tumor, Immunodeficiency, Infectional diseases
2.Immunosuppressant and indication a. Immunosuppressant*: Chemical agents: Cyclophosphamide, Cy Azathioprine, Aza Hormone: steroids Microbiological agents: CyclosporineA(CsA), Tacrolimus, FK-506 b. Indication: Organ transplantation Hypersensitivity diseases Autoimmune diseases Infectious diseases
Cyclosporin Azathioprine Tc IL-2 IFN IL-2R Th Steroids proliferation CD4 CD8 M TCR-CD3 TCR-CD3 APC Tc MHC-II MHC-I Tc Graft cells Immunosuppression with Drugs
Ag APC TH MHC TCR B7 CD28 抑制免疫应答: Hypersensitivity Disease Autoimmunity Disease Graft rejection responses inactivation Anti-B7Ab CTLA4 Ig Anti-CD28 • 阻断co-stimulatory signals
3.Immunomodulator and the use of them a. Biological response modifier, BRM b.Classification and function of BRM
b.Classification and function of BRM 1. Immunoreconstitution: hemopoietic stem cell and thymus 2. Monoclonal antibodies (McAb) and targeted drug McAb: Anti-CD3, Anti-CD4, Anti-CD8 Targeted drug*: Immunotoxin, IT Immunoconjugate, Radioimmunoconjugate 3. Cytokines and actived immune cells Cytokines*: Ils, IFN, TNF, CSF, TGF and Small molecular polypeptides. Immune cells: LAK, TIL 4. Tumor vaccine 5. Gene therapy*: CK gene therapy
McAb-toxin McAb-medicine Tumor McAb-isotope McAb-enzyme
Cytokine tumor type and results Cytokine effects and possible anti-tumor mechanisms Prolonged remissions of possible cytostatic hairy-cell leukemia effect on tumor weak effects on some increased expression of carcinoma MHC class I, cytostasis remission of peritoneal increased MHC class I and II carcinoma of the ovary macrophage activation Tc activation, cytostasis IFN IFN Remission in renal cancer T-cell activation and and melanoma proliferation NK-cell activation IL-2 ? Increased tumor cell adhension can reduce macrophage and lymphocyte malignant ascites activation TNF Cytokine therapy for tumors
Ag MHC TCR CTL Tumor cell signal1 CTLactivated Killer tumor cell signal2 CD28 B7 Ag MHC CTL TCR Tumor cell signal1 CTLactivated Killer tumor cell signal2 CD28 Enhancing immune response: Tumor immunity treatment TransfectionB7gene