g.2014-immuno~ (18.immunologic application-xm)

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

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Immunoprophylaxis


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.


Natural active immunization Natural Immune Natural passive immunization Specific immune response

Artificial active immunization Artificial Immune Artificial passive immunization


Vaccine induce immune response to Infectious

pathogen. (Vaccination).

1. Artificial active immunization

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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 :

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(1) killed vaccines: pathogens are inactivated. rabies, salk polio, Japanese encephalitis,

hepatitis A, H1N1 .

Type of vaccine

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No mutation or reversion

Can be used with immuno-deficient patients

Sometimes better in tropics

stable and easy to preserve.

Advantages of inactivated vaccines:

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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

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limitations.

Inactivate vaccines can not enter cells, so the cellula

r immunity is weak.

Commonly Inactivate vaccines: typhoid, cholera,

whooping cough, rabies, hepatitis A,

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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:

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Deletion mutants:

Suppression unlikely (but caution in HIV) Viable but

growth restrictions.

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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 。


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

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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

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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

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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


Production: formaldehyde or frozen-dry.

Lose toxicity

Immunogenicity reserved

　　The toxoid can induce antitoxin.

(3) Toxoid: (diphtheria, lockjaw) .

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Toxoid


proteins, protein or peptide of the pathogen can

activate the specific immune response to pathogen.

HBV surface protein HPV L1

(4) Subunit vaccines

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1.safe: no virulent, low hypersensitivity

2.low cost

3.easy to produce and modify

Disadvantage:

poorly immunogenic

Advantage of subunit vaccine:

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Conjugate vaccine

polysaccharide+diphitheria toxiod

Synthetic peptide vaccine

Recombinant antigen vaccine

Recombinant vector vaccine

DNA vaccine

Transgene plant vaccine


(1) safety

inducing infectious disease danger from improper

preparation reverting to wild type hypersensitivity.

The basic requirements of the vaccine

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(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.

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(1) Anti-infective:

(2) Anti – tumor: Therapeutic vaccine.

(3) Contraceptive vaccine.

Application of the vaccine

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Effect cells, moleculars are administrated to protect

the host from disese.

antibody: monoclone antibody, gene technologic

antibody IgG cytokines lymphocyte

2. Artificial passive immunization:

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Feature : The role of fast （ IgG ） , maintain a short time,

2-3 weeks.

Application ： Treatment or emergency prevention.

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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


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

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Emil von Behring (1845-1917)

Antibody (Antitoxin)


toxoidtoxin

Horse serum

Antitoxin

Hypersensitivity

antibody

antigen


Immunotherapy


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 .


Immunotherapy :

Artificially adjust the body's immune function to

achieve the purpose of treating disease.

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Preparation :

Antibody

CK – cytokines

Cell Therapy

Immunosuppressants

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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 ) ：

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Antitoxin, gamma globulin, antibacterial immune serum,

antiviral immune serum, anti - lymphocyte .

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Polyvalent antigen heterogeneous Mixture of

antibodies


Multiple epitopes

Mono-clone（ sensitized B cell ） Monoclonal

antibody


（ 2 ） Monoclonal antibodies ： Derived from a single clone and specific for a single

epitope.

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Cell engineering antibody——

hybridoma –monoclonal antibody


Myeloma cells

Activated, antibody-producing B cell

hybridoma


（ 3 ） Antibody targeted therapy:

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Target immunotherapy

Use of tumor specific/associated antigens monoclonal antibodies

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Tumor cell

enzyme

Ab-drug coupling

prodrug

drug

enzyme


CTLCD3

TUMORCELL

-S-S-

VH

CH1

VL

-S-S- CH1

Antigen A Antigen B

BsAbbispecific antibody;BsAb


(4) Cytokine immunotherapy

Exogenous cytokine therapy： Cytokine antagonist therapy：

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Exogenous cytokine therapy： GM-CSF 、 G-CSF: Leukopenia

EPO : Nephrogenic anemia

IFN-α: Leukemia, hepatitis, herpes zoster

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Cytokine antagonist therapy :

IL-1-receptor antagonist→inflammation and autoimmune diseases.

sIL-1R→ transplant rejection。sTNFR →rheumatoid arthritis RAⅠ

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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

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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)

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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!

g.2014-immuno~ (18.immunologic application-xm)

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