1. 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
2. Department of Immunology and Pathogen Biology, School of Medicine, Xi’an Jiaotong University
Immunoprophylaxis
3. 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.
4. 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
5. 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
6. 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 antibody
Complement-mediated lysis
CTL response: destroy the infected cell and terminate
the replication of virus
Neutralizing antibody :
9. 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
10. 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:
11. 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
12. Department of Immunology and Pathogen Biology, School of Medicine, Xi’an Jiaotong University
limitations.
Inactivate vaccines can not enter cells, so the
cellular immunity is weak.
Commonly Inactivate vaccines: typhoid, cholera,
whooping cough, rabies, hepatitis A,
13. 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:
14. 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.
15. 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 。
16. 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
17. 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 virus
from the community. (smallpox)
Advantages of Attenuated Vaccines II
18. 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 to
these patients).
Difficult to preserve.
Disadvantages of Live Attenuated Vaccine
19. 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
20. 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) .
21. Department of Immunology and Pathogen Biology, School of Medicine, Xi’an Jiaotong University
Toxoid
22. 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
23. 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:
24. 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
25. 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
26. 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.
27. 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
28. 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:
29. 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.
30. 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
31. 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
32. Department of Immunology and Pathogen Biology, School of Medicine, Xi’an Jiaotong University
Emil von Behring (1845-1917)
Antibody (Antitoxin)
33. Department of Immunology and Pathogen Biology, School of Medicine, Xi’an Jiaotong University
toxoidtoxin
Horse serum
Antitoxin
Hypersensitivity
antibody
antigen
34. Department of Immunology and Pathogen Biology, School of Medicine, Xi’an Jiaotong University
Immunotherapy
35. Department of Immunology and Pathogen Biology, School of Medicine, Xi’an Jiaotong University
Classification of immunotherapy
application
Immune 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 .
36. 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.
37. Department of Immunology and Pathogen Biology, School of Medicine, Xi’an Jiaotong University
Preparation :
Antibody
CK – cytokines
Cell Therapy
Immunosuppressants
38. 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 ) :
39. Department of Immunology and Pathogen Biology, School of Medicine, Xi’an Jiaotong University
Antitoxin, gamma globulin, antibacterial immune serum,
antiviral immune serum, anti - lymphocyte .
40. Department of Immunology and Pathogen Biology, School of Medicine, Xi’an Jiaotong University
Polyvalent
antigen heterogeneous
Mixture of
antibodies
41. Department of Immunology and Pathogen Biology, School of Medicine, Xi’an Jiaotong University
Multiple
epitopes
Mono-clone
( sensitized B cell ) Monoclonal
antibody
42. 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.
44. Department of Immunology and Pathogen Biology, School of Medicine, Xi’an Jiaotong University
Cell engineering antibody——
hybridoma –monoclonal antibody
45. Department of Immunology and Pathogen Biology, School of Medicine, Xi’an Jiaotong University
Myeloma cells
Activated, antibody-producing B cell
hybridoma
46. Department of Immunology and Pathogen Biology, School of Medicine, Xi’an Jiaotong University
( 3 ) Antibody targeted therapy:
47. Department of Immunology and Pathogen Biology, School of Medicine, Xi’an Jiaotong University
Target immunotherapy
Use of tumor specific/associated antigens monoclonal antibodies
48. Department of Immunology and Pathogen Biology, School of Medicine, Xi’an Jiaotong University
Tumor cell
enzyme
Ab-drug coupling
prodrug
drug
enzyme
49. Department of Immunology and Pathogen Biology, School of Medicine, Xi’an Jiaotong University
CTL
CD3
TUMOR
CELL
-S-S-
VH
CH1
VL
-S-S-
CH1
Antigen A Antigen B
BsAb
bispecific antibody;BsAb
50. Department of Immunology and Pathogen Biology, School of Medicine, Xi’an Jiaotong University
(4) Cytokine immunotherapy
Exogenous cytokine therapy :
Cytokine antagonist therapy :
51. 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
52. 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
53. 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
54. 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)
55. Department of Immunology and Pathogen Biology, School of Medicine, Xi’an Jiaotong University
More info:http://immunology.xjtu.edu.cn/lesson2005mianyizhiliaoINDEX.HTM
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