Chapter 21: Immunoprophylaxis and Immunotherapy
I. Immunoprophylaxis
II. Immunotherapy
I. ImmunoprophylaxisConception
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
Immunity can be acquired through active and passive immunization
Type acquired through
Active immunization: Natural infection or inapparent infection Artificial infection: vaccine, toxoid, attenuated organisms inactivated organisms purified microbioal macromoleculesPassive immunization: Natural maternal antibody Artificial immune serum
I. ImmunoprophylaxisConception
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
Artificial active Artificial passive immunization immunization
Injecting agents: Ag (vaccines, toxids) Ab (antitoxin, antiserum) Producting time: slow (induction phase:1-4W) at oncePersistenting time: long (months or years) slow (2weeks or months)The main application: specific prophylaxis urgent prophylaxis or (infectious diseases) treatment
I. ImmunoprophylaxisConception
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 producta. Vaccine: Live vaccine (attenuated vaccine) Killed vaccine Comparison*:b. Toxoid: TAT, DATc. New vaccine: Live vaccine Chemical vaccine or subunit vaccine Compound vaccine Genetic engineering vaccine Anti-idiotype vaccine
死疫苗和活疫苗的比较
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
Recombinant vaccine
DNA from pathogen
Plasmid
Vaccinia promoter
Ligation
Plasmid
Recombinantplasmid
Vaccinia virus
transfection infection
Animal-cell culture
Recombinant vaccinia
Anti-idiotype antibodies as vaccine
antibodyantigen
Antigen may be protein,carbohydrate,etc.
Antigenicdeterminant
Miceimmunized idiotype1
First antibody selectedfor high affinity forimmunizing antigen,made monoclonal
Anti-idiotype antibodiesRaised against idiotype 1
Second antibodiesscreened for similarityto original antigen
Anti-idiotype 1
Anti-idiotype 1
like antigen unlike antigen
vaccine
II. ImmunotherapyConception
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
Immunosuppression with Drugs
Steroids
APC
Graft cells
MHC-ITCR-CD3
CD8
Tc
Tc
Th proliferation
Cyclosporin Azathioprine
M
TCR-CD3
CD4
MHC-II
Tc
IL-2R
IFN IL-2
inactivation
抑制免疫应答:抑制免疫应答: Hypersensitivity DiseaseHypersensitivity Disease Autoimmunity DiseaseAutoimmunity Disease Graft rejection responsesGraft rejection responses
Anti-B7AbCTLA4 IgAnti-CD28
阻断 co-stimulatory signals
THAPC MHC TCR
Ag
CD28
B7
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
Tumor
McAb-toxin
McAb-enzyme
McAb-medicine
McAb-isotope
Cytokine therapy for tumorsCytokine tumor type and results Cytokine effects and possible anti-tumor mechanisms Prolonged remissions of possible cytostatic
hairy-cell leukemia effect on tumorweak 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
IL-2Remission in renal cancer T-cell activation and and melanoma proliferation NK-cell activation
TNF ? Increased tumor cell adhensioncan reduce macrophage and lymphocyte malignant ascites activation
Enhancing immune responseEnhancing immune response :: Tumor immunity treatmentTumor immunity treatment
B7
TransfectionB7gene
CTLMHC TCR
Ag
CD28
Tumor cellsignal1
signal2
CTLMHC TCR
Ag
CD28
Tumor cellsignal1
signal2
CTLactivatedKiller tumor cell
CTLactivatedKiller tumor cell