免疫预防与免疫治疗陈建忠.ppt

Immune prophylaxis and Immunotherapy,Immunoprophylaxis,I. Introduction,For centuries we have known that individuals who recover from certain diseases are protected from reinfection. Ancient Chinese and Arabic writings recorded the deliberate transmission of smallpox to healthy persons by inhalation of powdered smallpox crusts from diseased persons.,Goal of immunization The goal of immunization in any one individual is the prevention of disease. The goal of immunization of population is the eradication of disease. In 1980, WHO announced that smallpox has been eradicated in the world.,The last known person in the world to have a natural case of smallpox. Variola minor in 23-year-old Ali Maow Maalin, Merka, Somalia CDC In 1980, WHO announced that smallpox has been eradicated in the world.,Ways of acquiring specific immunity,II. Essential requirements of vaccine,III. Artificial active immunization,Administration of an antigen for active production of immunity. Active immunization results in the production of antibodies directed against the infecting agent or its toxic products; it may also initiate cellular immunity.,Agents used in active immunization,The agent used for artificial active immunization is called vaccine. inactivated vaccine (Dead vaccine ) Standard strain of a microbe is killed and severed as an immunogen. For example: cholera vaccine Japanese encephalitis vaccine rabies vaccine typhoid vaccine,Agents used in active immunization 2. Live-attenuated vaccine It is more effective than dead vaccine. A single dose of a live vaccine often suffices for reliable immunization. Live vaccine must be properly stored to retain effectiveness.,Viruses are traditionally attenuated by selecting for growth in nonhuman cells,Viruses are traditionally attenuated by selecting for growth in nonhuman cells,Examples of live vaccines,Measles virus vaccine Polio virus vaccine (oral) bacillus Calmette-Guerin (BCG) vaccine Typhoid vaccine (oral live attenuated bacteria),Live vaccine dead vaccine,Route of administration imitating natural injecting infection subcutaneously Doses of administration small large Times of administration once twice or more Side effect slight severe Duration of immunity long short 35 years several months1 year Mutation possible impossible Preservation of vaccine at 4C easy to preserve or lyophilization,Comparison between live and dead vaccines,3. Toxoid,Exotoxin can be converted into nontoxic but still immunogenic preparations called toxoid. Examples:Diphtheria toxoid, Tetanus toxoid,IV. Artificial passive immunization,Immunization may be accomplished passively by administering either performed immunoreactive serum (Abs, CKs) or cells. Passive immunization is thus useful for individuals who cannot form Abs or for the non-immunocompromised host who might develop disease before active immunization could stimulate Ab production, which usually requires at least 7-10 days.,Agents used in passive immunization,1. Antitoxins They are usually prepared from hyperimmunized horses or rabbits. Antitoxins consist of toxin-neutralizing Abs specific for a given toxin. Examples of antitoxins: Diphtheria antitoxin Tetanus antitoxin,2. Human Ig,This preparation is derived from pooled plasma. Standard Ig for intramuscular use (IMIG) Standard Ig for intravenous use (IVIG) IVIG has been adapted to intravenous use by eliminating high-molecular-weight complexes that may activate complement in the recipient. Specific Ig, e.g. HBIg,3. Cytokines IL-2, IFN, CSF 4. Monoclonal antibody McAb may be used either alone, or coupled to drugs, toxins, cytokines or isotopes.,Active immunization Passive immunization,Administration Ag (vaccines, toxoid) Ab (antitoxin, -globulin) Production of slowly immediately immunity Duration of long (from several short (2 weeks to immunity months to years) months) Usage immunoprophylaxis emergency prophylaxis and therapy,Comparison between active and passive immunization,V. Adjuvant,A substance that, when mixed with an immunogen, enhances the immune response against the immunogen.,VI. Planned immunization,A rational program of immunization against infectious diseases has been committed in children worldwide when many of the most damaging and preventable infections normally appear. The program of childhood immunization is called planned immunization.,Planned immunization schedule in China,VII. Development of novel vaccines,Subunit vaccine These vaccines are in use which make use of antigens either purified from microorganisms or produced by recombinant DNA technology. e.g. HBV vaccine (HBsAg),Conjugate vaccine,These vaccines are obtained by conjugating the purified polysaccharides (bacterial capsular polysaccharides) to carrier proteins such as diphtheria toxoid.,Synthetic peptide vaccine,Small antigens can be made synthetically. e.g. HBs vaccine Synthetic B-and T-cell epitopes can be combined in various ways to optimize the resulting immune response.,Genetic engineering vaccine,Recombinant antigen vaccine To clone the selected gene into a vector (yeast) to cultureto purify the Ag from the culture supernatantantigen Recombinant vector vaccine To insert the desired gene into a vector (vaccinia) which can then be injected into the patient, allowed to replicate, express the gene and produce large amounts of the antigen.,DNA vaccine,These are based on the discovery that when DNA encoding a chosen microbial protein is injected intramuscularly or intradermally, host cells can take up these artificial genes and express the foreign protein for several weeks. Depending on the protein expressed, this can induce specific humoral or cellular immunity, or both.,Transgenic plant vaccine,Genes encoding the protective immunogens are transduced into plant cells. Such as tomato, potato, and banana, etc.,Reverse vaccinology for identification novel vaccine antigen,Preventative Vaccine,Therapeutic Vaccine,VIII. Application of vaccines,Anti-infection HIV HCV SARS,VIII. Application of vaccines,2. Anti-tumor 3. Birth control Vaccines based on the chain of HCG, coupled to tetanus or diphtheria toxoid, have been extremely successful in preventing conception in humans. 4. Prevention of immunopathologic damage,(Institute of Immunology, ZJU),Immunotherapy,Conception of immunotherapy Immunotherapy is the approach to balance or intervene the immunologic function in order to fight against the disease by the principle of immunology.,I. Conception and classification,B, Classification of Immunotherapy,II. Molecular Immunotherapy,1. Molecular Vaccine Synthetic peptide vaccine Recombinant vector vaccine DNA vaccine used as treatment of tumor and infection,II. Molecular Immunotherapy,2. Antibody-polyclonal Ab antitoxic serum placental gamma-globulin antibacterial immune serum antiviral immune serum anti-lymphocyte gamma-globulin, ALG,II. Molecular Immunotherapy,2. Antibody-Monoclonal antibody, mAb mAb against surface membrane molecules on lymphocytes：CD3 mAb against cytokines:TNF mAb-directed therapy mAb coupled to isotopes, drugs, toxins,Application of Ab in vitro: elimination of cancer cells in bone marrow or T cells to prevention GVHD,Monoclonal antibodies that recognize tumor-specific antigens might be used in a variety of ways to help eliminate tumors.,Examples of tumor antigens that have been targeted by monoclonal antibodies in therapeutic trials.,II. Molecular Immunotherapy,Chimeric Ab Humanized Ab (CDR-grafted Ab) Single chain Ab Bispecific Ab,2. Antibody-Genetic engineering Ab,II. Molecular Immunotherapy,Cytokine supplement and addition therapy IFN, IL-2, CSF Cytokine blockade and suppression anti-TNF IL-1Ra sIL-1R,3. Cytokines and their antagonists,II. Molecular Immunotherapy,EBV HPV HBV,