Basic immunology chapter ppts DZ 2010.ppt

Acknowledgements
 Addis Ababa University
 Jimma University
 Hawassa University
 Haramaya University
 University of Gondor
 American Society for clinical Pathology
 Center for Disease Control and Prevention Ethiopia

Learning Objectives
 Upon completion of this lecture and exercises the
student will be able to:
 Define vaccine
 List various vaccine development techniques
 Describe Criteria for Effective Vaccines
 Differentiate between passive and active immunity
 Describe the difference between attenuated and
inactivated vaccines
 Weight the risks of vaccines for the individual against the
benefits of vaccinations for society

12.1. Introduction to Vaccines
12.2. Active and Passive Immunization
12.3. Designing Vaccines for Active Immunization
12.4. Whole-Organism Vaccines
12.5. Purified Macromolecules as Vaccines
12.6. Recombinant-Vector Vaccines
12.7. DNA Vaccines
12.8. Multivalent Subunit Vaccines
12. Outline

12.1.Introduction to Vaccines
 Vaccines –
 Biological substances that stimulate the person’s immune
system
 To produce an immune response identical to that
produced by the natural infection.
 Vaccines can
 Prevent the debilitating and, in some cases, fatal
infectious diseases.
 Help to eliminate the illness and disability of polio,
measles, and rubella

 Vaccines protect the
 Vaccinated individual,
 Protect society.
 A community with many vaccinated people
 Protects the few who cannot be vaccinated—such as
young children.
 Indirectly protects unvaccinated from exposure to
disease).= HERD IMMUNITY

 Aim of an ideal vaccine:
 To produce the same immune protection which usually
follows natural infection but without causing disease
 To generate long-lasting immunity
 To interrupt spread of infection

 Differences in epitopes recognized by T cells and B cells
has enabled to design vaccines that maximized activation
of both immune system arms.
 Differences in antigen-processing pathways became
evident, used techniques to design vaccines and to use
adjuvants that maximize antigen presentation with class I
or class II MHC molecules
 Genetic engineering techniques can be used to develop
vaccines to maximize the immune response to selected
epitopes and to simplify delivery of the vaccines.

 The World Health Organization (WHO) has stated that the
ideal vaccine would have the following properties:
 Affordable worldwide
 Heat stable
 Effective after a single dose
 Applicable to a number of diseases
 Administered by a mucosal route
 Suitable for administration early in life
12.2. Criteria for Effective Vaccines

 Many diseases stimulate an immune response in host,
 those who survive the disease are protected from second
infection – natural acquired active immunization
 the risk is many die before becoming immune
 Vaccinations uses
 Artificially acquired active immunity - is stimulated by initial
exposure to specific foreign macromolecules through
the use of vaccines, to artificially establish state of
immunity.
 Individuals, who have not had the disease, can be protected
even when exposed at later date

 Limitations of Active immunity
 developing an immune response does not = achieving
state of protective immunity
 vaccine can induce primary response but fail to induce
memory cells = host unprotected
 Various approaches used to effectively induce humoral and
cell-mediated immunity and the production of memory cells.

Ideal Vaccination Response

Artificially acquired passive immunity; the individual
receives protective
 Molecules (antibodies)Tetanus Anti-toxoid or
 Cell (lymphocytes) produced in another individual.
Naturally acquired passive immunity
 Refers to antibodies transferred from mother to fetus
across the placenta and to the newborn in colostrum
and breast milk during the first few months of life.
Passive immunization does not activate the immune system, it
generates no memory response and the protection provided is
transient

 Many common vaccines use
 inactivated (killed), but still antigenic or
 live/altered – attenuated microorganisms.
 Caused to loose pathogenicity (cultured in
abnormal conditions)
 substance (e.g., protein, polysaccharide) from
pathogen, capable of producing an immune response
 DNA vaccines currently being tested for human use
12.4. Designing Vaccines for Active
Immunization

 Attenuated organisms, for vaccines, lose ability to cause
significant disease (pathogenicity) but
 to attenuate, grow a pathogenic bacterium or virus for
prolonged periods under abnormal culture conditions
 retains capacity for short term growth within inoculated
host.
 capacity for transient growth, permits prolonged immune-
system exposure to attenuated epitopes, increased
immunogenicity and production of memory cells.
 As a consequence, these vaccines often require
only a single immunization.
 A major disadvantage is the possibility that they
will revert to a virulent form.
12.5. Whole organism vaccines

12.6. Purified Macromolecules as
Vaccines
 Derived from pathogens.
 Are specific, purified macromolecules .
 Avoid some risks associated with attenuated or killed whole
organism vaccines.
 Three general forms of such vaccines are in current use:
 inactivated exotoxins,
 capsular polysaccharides, and
 recombinant microbial antigens

Vaccines

 Isolate gene encoding immunogenic protein, clone it, and
express/insert in bacterial, yeast, or mammalian cells using
recombinant DNA technology.
 Example for human use is hepatitis B vaccine developed by
cloning the gene for surface antigen of hepatitis B virus
(HBsAg) and expressing it in yeast cells.
 The recombinant yeast cells are grown in large fermenters,
and HBsAg accumulates in the cells.
 The yeast cells is disrupted, releases the recombinant
HBsAg, which is purified by biochemical techniques.
Vaccines

 Genetic engineering techniques are a way to attenuate a
virus irreversibly by selectively removing genes that are
necessary for virulence.
 Genes encoding major antigen of virulent pathogens can be
added in high levels to attenuated viruses or bacteria.
 The attenuated organism serves as a vector, replicating
within the host and expressing the gene product of the
pathogen.
 Vaccinia virus, attenuated vaccine used to eradicate
smallpox, was widely employed as a vector vaccine.

Source: Kuby Immunology 2007, 5th
ed

12.8. DNA Vaccines
 Plasmids are easily manufactured in large amounts
 DNA is very stable, resists temperature extremes so
storage and transport are straight forward
 DNA sequence can be changed easily in the laboratory.
So can respond to changes in the infectious agent
 The DNA is injected into a person’s muscle. It integrates
into the sysnthesis of the muscle cell, stimulating a
strong Tc cell response with good memory.

plasmid
Gene
for
antigen
Muscle cell expresses protein; antibody’s made; & CTL response
Muscle cell
12.8. DNA Vaccines

DNA vaccines produce a situation that reproduces a
virally-infected cell
Gives:
• Broad based immune response
• Long lasting CTL response
Advantage of new DNA vaccine for flu:
CTL response can be against internal protein
In mice a nucleoprotein DNA vaccine is effective against a
range of viruses with different hemagglutinins
12.8. DNA Vaccines

 Mixtures of plasmids encoding many different viral protein
fragments can produce a broad spectrum vaccine
 Plasmid does not replicate. It encodes only proteins of
interest
 Vector has no protein component to stimulate an immune
response.
 However, there is a CTL response against the pathogen’s
antigens.
 These CTL responses have advantage of protection against
diseases caused by certain obligate intracellular pathogens
(e.g. Mycobacterium tuberculosis)
12.8. DNA Vaccines

 Potential Risks
 Potential integration of plasmid into host genome leading
to insertional mutagenesis
 Induction of autoimmune responses (e.g. pathogenic anti
DNA antibodies)
 Induction of immunologic tolerance (e.g. where the
expression of the antigen in the host may lead to specific
non-responsiveness to that antigen)
12.8. DNA Vaccines

 A method for constructing synthetic peptide vaccines that
contain both immunodominant for both
 B-cell and
 T-cell epitopes.
 If a CTL response is desired, vaccine must be delivered
intra-cellularly so that the peptides can be processed
and presented together with class I MHC molecules.

 Techniques to develop multivalent vaccines that present
multiple copies of a given peptide or a mixture of peptides
 solid matrix–antibody-antigen (SMAA) complexes
attaching monoclonal antibodies to particulate solid
matrices and
 then saturating the antibody with the desired antigen.
 different specificity monoclonal antibodies on solid matrix,
permits binding a mixture of peptides or proteins,
provides immunodominant epitopes for both T cells and B
cells,
 multivalent complexes shown to induce vigorous humoral
and cell-mediated responses.

Summary
 A state of immunity can be induced by passive or active
immunization
 a) Short-term passive immunization is induced by
transfer of preformed antibodies.
 b) Infection or inoculation achieves long-term active
immunization.
 Three types of vaccines are currently used in humans:
 attenuated (avirulent) microorganisms,
 inactivated (killed) microorganisms, or
 purified macromolecules.

 Protein components of pathogens expressed in cell culture
may be effective vaccines.
 Recombinant vectors, including viruses or bacteria,
engineered to carry genes from infectious microorganisms,
maximize cell-mediated immunity to the encoded antigens
 Plasmid DNA encoding a protein antigen from a pathogen
can serve as an effective vaccine inducing both humoral
and cell-mediated immunity.
Summary

Summary
Source: Kuby Immunology 2007 5th
ed

Review question
 List various vaccine development techniques
 Describe Criteria for Effective Vaccines
 Differentiate between passive and active immunity
 Describe the difference between attenuated and
inactivated vaccines
 Give account advantage and disadvantage of DNA
vaccine

Reference
1. Kuby; Goldsby et. al. Immunology. 2007 (5th
ed)
2. Tizard. Immunology an introduction,4th
edition ,Saunders publishing,1994
3. Naville J. Bryant Laboratory Immunology and Serology 3rd
edition.
Serological services Ltd.Toronto,Ontario,Canada,1992
4. Abul K. Abbas and Andrew H. Lichtman. Cellular And Molecular
Immunology 2008, 5th
edition
5. Mary T. Keogan, Eleanor M. Wallace and Paula O’Leary Concise clinical
immunology for health professionals , 2006
6. Ivan M. Roitt and Peter J. Delves Essential immunology 2001, 3rd
ed
7. Reginald Gorczynski and Jacqueline Stanley, Clinical immunology 1990.

Basic immunology chapter ppts DZ 2010.ppt

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