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Department of Immunology and Pathogen Biology, School of Medicine, Xi’an Jiaotong University
Immunoprophylaxis and Immunotherapy
Why do they not want to play with my kids?
They should be vaccinated first
Department of Immunology and Pathogen Biology, School of Medicine, Xi’an Jiaotong University
Immunoprophylaxis
Department of Immunology and Pathogen Biology, School of Medicine, Xi’an Jiaotong University
Immunity to infectious microorganisms can be achieved by active or passive immunization. In each case, immunity can be acquired either by natural processes or by artificial means.
The agents used for inducing passive immunity include antibodies from humans or animals, whereas active immunization is achieved by inoculation with microbial pathogens that induce immunity but do not cause disease.
Department of Immunology and Pathogen Biology, School of Medicine, Xi’an Jiaotong University
Natural active immunization Natural Immune Natural passive immunization Specific immune response
Artificial active immunization Artificial Immune Artificial passive immunization
Department of Immunology and Pathogen Biology, School of Medicine, Xi’an Jiaotong University
Vaccine induce immune response to Infectious
pathogen. (Vaccination).
1. Artificial active immunization
Department of Immunology and Pathogen Biology, School of Medicine, Xi’an Jiaotong University
Binding of antibody to site on virus surface - block interaction with receptor.Aggregation of virus by polyvalent antibodyComplement-mediated lysis
CTL response: destroy the infected cell and terminate
the replication of virus
Neutralizing antibody :
Department of Immunology and Pathogen Biology, School of Medicine, Xi’an Jiaotong University
Department of Immunology and Pathogen Biology, School of Medicine, Xi’an Jiaotong University
Department of Immunology and Pathogen Biology, School of Medicine, Xi’an Jiaotong University
(1) killed vaccines: pathogens are inactivated. rabies, salk polio, Japanese encephalitis,
hepatitis A, H1N1 .
Type of vaccine
Department of Immunology and Pathogen Biology, School of Medicine, Xi’an Jiaotong University
No mutation or reversion
Can be used with immuno-deficient patients
Sometimes better in tropics
stable and easy to preserve.
Advantages of inactivated vaccines:
Department of Immunology and Pathogen Biology, School of Medicine, Xi’an Jiaotong University
Inactivation may alter antigenicity
Many vaccinees do not raise immunity (Poor immune effects).
Injections need to be repeated several times.
No local immunity (important)
Higher cost
The side effects are more serious.
Failure in inactivation and immunization with virulent virus.
Disadvantages of inactivated vaccines
Department of Immunology and Pathogen Biology, School of Medicine, Xi’an Jiaotong University
limitations.
Inactivate vaccines can not enter cells, so the cellula
r immunity is weak.
Commonly Inactivate vaccines: typhoid, cholera,
whooping cough, rabies, hepatitis A,
Department of Immunology and Pathogen Biology, School of Medicine, Xi’an Jiaotong University
include: 1) bacterials: Bacillus Calmette-Guerin (mycobacterium tuberculosis), 2) virus: Sabin polio, MMR (measles,mumps,rubella), VZV (varicella zoster virus)
Production: passage progressively, passage in cold temperature, select mutation strain.
(2)Live-attenuated vaccine:
Department of Immunology and Pathogen Biology, School of Medicine, Xi’an Jiaotong University
Deletion mutants:
Suppression unlikely (but caution in HIV) Viable but
growth restrictions.
Mycobacterium bovis
Placed in a medium containing bile, gradually increasing the concentration of bile
13 years
Bacillus Calmette-Guerin (BCG)
Adaptive growth of Mycobacterium bovis in bile 。
Department of Immunology and Pathogen Biology, School of Medicine, Xi’an Jiaotong University
Activates all phases of immune system. Can get
humoral IgG and local IgA.
Raises immune response to all protective antigens.
Inactivation may alter antigenicity.
Good immune effects, maintaining a long time.
Advantages of Attenuated Vaccines I
Department of Immunology and Pathogen Biology, School of Medicine, Xi’an Jiaotong University
Low cost.Quick immunity in majority of vaccinees.Easy transport in field.Can lead to elimination of wild type virusfrom the community. (smallpox)
Advantages of Attenuated Vaccines II
Department of Immunology and Pathogen Biology, School of Medicine, Xi’an Jiaotong University
Mutation; reversion to virulence (often frequent).May be back-mutated.Problem in immunodeficiency disease (may spread tothese patients).Difficult to preserve.
Disadvantages of Live Attenuated Vaccine
Department of Immunology and Pathogen Biology, School of Medicine, Xi’an Jiaotong University
Difference Inactivate vaccines Attenuated Vaccine
Preparation Dead virulent strain Attenuated or avirulent
Inoculation methods Subcutaneous injection
Simulate the natural route of infection
Vaccination and vaccine dose
dose higher , 2 to 3 times dose lower, 1 times.
Side effect Serious Slight
Immune effect maintaining several months to 1 year
maintaining 3 to 5 years or longer
Vaccines preservation Easy Not easy
Difference between Attenuated Vaccine and Inactivate vaccines
Department of Immunology and Pathogen Biology, School of Medicine, Xi’an Jiaotong University
Production: formaldehyde or frozen-dry.
Lose toxicity
Immunogenicity reserved
The toxoid can induce antitoxin.
(3) Toxoid: (diphtheria, lockjaw) .
Department of Immunology and Pathogen Biology, School of Medicine, Xi’an Jiaotong University
Toxoid
Department of Immunology and Pathogen Biology, School of Medicine, Xi’an Jiaotong University
proteins, protein or peptide of the pathogen can
activate the specific immune response to pathogen.
HBV surface protein HPV L1
(4) Subunit vaccines
Department of Immunology and Pathogen Biology, School of Medicine, Xi’an Jiaotong University
1.safe: no virulent, low hypersensitivity
2.low cost
3.easy to produce and modify
Disadvantage:
poorly immunogenic
Advantage of subunit vaccine:
Department of Immunology and Pathogen Biology, School of Medicine, Xi’an Jiaotong University
Conjugate vaccine
polysaccharide+diphitheria toxiod
Synthetic peptide vaccine
Recombinant antigen vaccine
Recombinant vector vaccine
DNA vaccine
Transgene plant vaccine
Department of Immunology and Pathogen Biology, School of Medicine, Xi’an Jiaotong University
(1) safety
inducing infectious disease danger from improper
preparation reverting to wild type hypersensitivity.
The basic requirements of the vaccine
Department of Immunology and Pathogen Biology, School of Medicine, Xi’an Jiaotong University
(2) efficiency
unable to induce effective CTL response (killed
vaccine,subunit vaccines and new vaccines).
unable to trigger immune response like naturally
infection unknown to the antigen properties.
(3) practicality: easy to store and transport, low prices.
Department of Immunology and Pathogen Biology, School of Medicine, Xi’an Jiaotong University
(1) Anti-infective:
(2) Anti – tumor: Therapeutic vaccine.
(3) Contraceptive vaccine.
Application of the vaccine
Department of Immunology and Pathogen Biology, School of Medicine, Xi’an Jiaotong University
Effect cells, moleculars are administrated to protect
the host from disese.
antibody: monoclone antibody, gene technologic
antibody IgG cytokines lymphocyte
2. Artificial passive immunization:
Department of Immunology and Pathogen Biology, School of Medicine, Xi’an Jiaotong University
Feature : The role of fast ( IgG ) , maintain a short time,
2-3 weeks.
Application : Treatment or emergency prevention.
Department of Immunology and Pathogen Biology, School of Medicine, Xi’an Jiaotong University
Emil von Behring :Confirmed the therapeutic effects of the
anti-toxin for diphtheria and tetanus.
Nobel Prize in Physiology or Medicine 1901.
Emil von Behring 1854 - 1917
Passive Immunity
Department of Immunology and Pathogen Biology, School of Medicine, Xi’an Jiaotong University
Antitoxin: Preparations of human immunoglobulin: Placental globulin, Plasma gamma globulin.
Antibacterial sera, anti-viral sera
Preparations of cytokine :
Preparations of monoclonal antibody :
Biological products of Artificial passive immunization
Department of Immunology and Pathogen Biology, School of Medicine, Xi’an Jiaotong University
Emil von Behring (1845-1917)
Antibody (Antitoxin)
Department of Immunology and Pathogen Biology, School of Medicine, Xi’an Jiaotong University
toxoidtoxin
Horse serum
Antitoxin
Hypersensitivity
antibody
antigen
Department of Immunology and Pathogen Biology, School of Medicine, Xi’an Jiaotong University
Immunotherapy
Department of Immunology and Pathogen Biology, School of Medicine, Xi’an Jiaotong University
Classification of immunotherapy
applicationImmune enhancement therapy Infection, cancer, immunodeficiency disease
Immunosuppressive therapy
Hypersensitivity, autoimmune diseases, transplant rejection, inflammation treatment
Specific therapy Preparation of antigen-specific: Vaccine, the effect of the product, the monoclonal antibody.
Non-specific therapy Adjust the immune function, non-antigen-specific
Active immunotherapy Preparation of the immunogenicity, take the initiative to produce specific immunity
Passive immunotherapy
Substance of immune effector, Direct play of immune effector .
Department of Immunology and Pathogen Biology, School of Medicine, Xi’an Jiaotong University
Immunotherapy :
Artificially adjust the body's immune function to
achieve the purpose of treating disease.
Department of Immunology and Pathogen Biology, School of Medicine, Xi’an Jiaotong University
Preparation :
Antibody
CK – cytokines
Cell Therapy
Immunosuppressants
Department of Immunology and Pathogen Biology, School of Medicine, Xi’an Jiaotong University
Most antigens offer multiple epitopes and induce
proliferation and differentiation of a variety of
B-cell clones, The resulting serum antibodies are
comprising a mixture of antibodies, each specific
for one epitope.
( 1 ) Polyclonal antibody ( immune serum ) :
Department of Immunology and Pathogen Biology, School of Medicine, Xi’an Jiaotong University
Antitoxin, gamma globulin, antibacterial immune serum,
antiviral immune serum, anti - lymphocyte .
Department of Immunology and Pathogen Biology, School of Medicine, Xi’an Jiaotong University
Polyvalent antigen heterogeneous Mixture of
antibodies
Department of Immunology and Pathogen Biology, School of Medicine, Xi’an Jiaotong University
Multiple epitopes
Mono-clone( sensitized B cell ) Monoclonal
antibody
Department of Immunology and Pathogen Biology, School of Medicine, Xi’an Jiaotong University
( 2 ) Monoclonal antibodies : Derived from a single clone and specific for a single
epitope.
Department of Immunology and Pathogen Biology, School of Medicine, Xi’an Jiaotong University
Department of Immunology and Pathogen Biology, School of Medicine, Xi’an Jiaotong University
Cell engineering antibody——
hybridoma –monoclonal antibody
Department of Immunology and Pathogen Biology, School of Medicine, Xi’an Jiaotong University
Myeloma cells
Activated, antibody-producing B cell
hybridoma
Department of Immunology and Pathogen Biology, School of Medicine, Xi’an Jiaotong University
( 3 ) Antibody targeted therapy:
Department of Immunology and Pathogen Biology, School of Medicine, Xi’an Jiaotong University
Target immunotherapy
Use of tumor specific/associated antigens monoclonal antibodies
Department of Immunology and Pathogen Biology, School of Medicine, Xi’an Jiaotong University
Tumor cell
enzyme
Ab-drug coupling
prodrug
drug
enzyme
Department of Immunology and Pathogen Biology, School of Medicine, Xi’an Jiaotong University
CTLCD3
TUMORCELL
-S-S-
VH
CH1
VL
-S-S- CH1
Antigen A Antigen B
BsAbbispecific antibody;BsAb
Department of Immunology and Pathogen Biology, School of Medicine, Xi’an Jiaotong University
(4) Cytokine immunotherapy
Exogenous cytokine therapy: Cytokine antagonist therapy:
Department of Immunology and Pathogen Biology, School of Medicine, Xi’an Jiaotong University
Exogenous cytokine therapy: GM-CSF 、 G-CSF: Leukopenia
EPO : Nephrogenic anemia
IFN-α: Leukemia, hepatitis, herpes zoster
Department of Immunology and Pathogen Biology, School of Medicine, Xi’an Jiaotong University
Cytokine antagonist therapy :
IL-1-receptor antagonist→inflammation and autoimmune diseases.
sIL-1R→ transplant rejection。sTNFR →rheumatoid arthritis RAⅠ
Department of Immunology and Pathogen Biology, School of Medicine, Xi’an Jiaotong University
Adoptive immunotherapy : After activation and proliferation
of lymphocytes in vitro, lymphocytes reinfusion.
T cell TIL cell → Reinfusion
NK LAK cell→ Reinfusion
IL-2
IL-2
( 5 ) Immune effector cells : NK 、 LAK 、TIL
Department of Immunology and Pathogen Biology, School of Medicine, Xi’an Jiaotong University
TILs are CD8+ T cells isolated from patient tumor
samples, some of which react with tumor antigens.
After activation with IL-2, they are infused into the
patient.
As with LAK therapy there is significant toxicity if
high doses of IL-2 are used.
Tumor infiltrating lymphocytes (TILs)
Department of Immunology and Pathogen Biology, School of Medicine, Xi’an Jiaotong University More info:http://immunology.xjtu.edu.cn/lesson2005\mianyizhiliao\INDEX.HTM
Thanks!