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Chpt 18


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What is a vaccine?
A foreign substance that induces a protective response but doesn't harm the recipient.
What is immunization?
Conference of resistance/immunity to infectious microorganisms, either passively or actively.
What is passive immunization?
Transfer of pre-formed antibodies
What are two ways of conferring Passive Immunity?
-Natural transfer - maternal antibodies, IgG and IgA pass from Mom to fetus across placenta, or milk.

-Inject pre-formed antibody.
3 reasons/times to passively immunize:
1. Deficient Ab synthesis - Bcell defects or immunodeficiency.

2. Need quick Ab generation for impending exposure (business trip)

3. Stepped on a nail - quick Ab response to neutralize toxin.
Does passive immunization initiate immune response?

No; therefore, no memory response; Antibody protection is transient
Disadvantages of Passive Immunization:
1. No memory
2. Temporary - only lasts about 2 wks.
3. Expensive - purified human Ab
4. Allergic response - horse antiserum can cause type 1/type 3 hypersensitiv.
Purpose of Active Immunization
To elicit protective immunity and memory response - permanent protection from pathogens
2 ways to achieve active immunity:
-natural infection
-artificial infection - injection
Why do kids need booster shots?

Why wait for MMR in america, but not in 3rd world countries?
Infants - month 1, maternal Ab still exists; blocks epitopes on vaccine so less response occurs.

Boosters achieve adequete response as maternal Ab goes away.

Less incidence of MMR here; more there.
What is herd immunity?
Protection of a poorly-responsive individual; the population responds well and is less likely to spread the disease to the poor-responder.
4 factors to consider in designing a vaccine:
1. Pathogenesis of the organism
2. Immune response generated
3. Memory cells
4. Antigenicity of the molecule used
Why consider organism pathogenicity a in vaccine design?
-the incubation time before symptoms are seen is a factor in deciding which immune response to induce.

e.g., flu incubates very short; need high antibody all the time. but polio is long; can wait for memory cell response to generate antibody.
Why consider memory in vaccine design?
some pathogens might induce an immune response, but failure to induce memory response. have to take into account.
purpose of FLU vaccine compared to POLIO:
flu - short incub. period, maintain high antibody levels with repeated immunization.

polio - generate high immunologic MEMORY because long incub. period allows antibody production naturally.
what is an inactivated whole-organism vaccine?

A dead bacteria or virus; cannot proliferate, but its morphology is preserved.

Attenuated is alive but avirulent, non-toxic.
Disadvantages of Attenuated vaccines
Can REVERT to pathogenic organism and cause disease.
Why do we only give the Inactivated (dead) Polio virus now, now the attenuated?
attenuated can revert to virulent form; makes its way into water stores and back into population.
4 disadvantages of attenuated vaccines:
1. MAJOR: reversion to virulent form
2. Hard to ship - unstable.
3. causes side effects
4. Cannot be given to IMMUNODEFICIENT patients because it requires an active immune response
How are inactivated vaccines made?
by heat or chemical.
disadvantages of inactivated vaccines:
-no growth within host; requires booster shots for ample immune response.
-mostly induce HUMORAL response; less cell-mediated or IgA -> no IgA at mucosa
which vaccine is used now, Sabin/attenuated, or

Salk - inactivated. does not revert.

However, it doesn't cause production of IgA at the mucosal level, you have to inject it, and boosters are necessary.
3 types of purified macromolecule vaccines:
-polysaccharides from capsules

-inactivated exotoxins

-recombinant microbial antigens
what does the immune response to a polio vaccine look like?
-Rapid increase of serum Ab immediately; peaks/declines after 2 wks.

-Imuno memory maxes at 6 mo; levels off to persist for years.
what is a Toxoid?

2 examples:
Inactivated toxin

what is a polysaccharide vaccine?

what type of response it induces?
-use bacterial cell-surface molecules (capsule antigens) to induce a Bcell response, with IgM.

No class switching, affinity mat, etc.
How can you activate Th cells with polysaccharide antigens?
Link to protein carrier.
What's an example of a protein carrier-polysaccharide vaccine?
Haemophilus influenzae polysacch. + Tetanus protein. Activates Bcells AND Thelper for class switching IgM->IgG
How is a Toxoid vaccine made?
-purify exotoxin from bacteria.
-inactivate with formaldehyde
major limitation of polysaccharide vaccines:
only activate thymus-independent Bcells; no memory generated.
how can you produce pathogen proteins with recombinant techniques?
insert the gene for a particular surface antigen into a yeast, bacterial, or any expression system; it will make the protein you harvest it and inject it.
What type of vaccine is the Hepatitis B vaccine?
recombinant protein; made by inserting SURFACE ANTIGEN gene into yeast cells, generating the protein, harvesting and purifying it.
4types of PURIFIED MOLECULES vaccines:
1. Polysaccharide
2. Polysaccharide-protein carrier
3. Surface antigen (recomb. production)
4. Toxoid
2 types of protein that can surve as purified molecule vaccines:
1. Toxoid (inactivated exotoxin)
2. Surface Ag (HepB; recombinant prod)
Principal of Recombinant-Vector Vaccines:
-Insert gene for major Ag of v. virulant pathogen into ATTENUATED virus or bacteria.

-Administer vaccine; like giving an attenuated vaccine, AND activates Tcell response because of intracellular replication and antigen expression.
what type of vaccine is the
Vaccinia vaccine?
a Vector vaccine for smallpox.
how is the vaccinia virus generated?
1. Insert an Antigen gene into a plasmid vector.
2. Incubate the Vaccinia virus, recombinant plasmid, and live cells.
3. Select cells containing recombinant vaccinia virus.
how are DNA vaccines constructed/delivered?

1. Create recombinant plasmid DNA encoding antigenic proteins.
2. Inject directly into muscle with needle or GENE GUN.

Result: muscle/dendritic cells express Ag and induce humoral AND cell-mediated response.
How can you jazz up DNA vaccines?
Coat gold beads with DNA plasmid. Deliver with gene gun. Rapid delivery.


Add genes for cytokines to direct which immune response you want (Th1 or Th2)
What limitation of other vaccines does MULTIVALENT subunit vaccines overcome?
Purified molecule, DNA, and whole-body vaccines are poorly immunogenic - they only have one epitope and are small.
What is the purpose of multivalent subunit vaccines?
They possess immunodominant epitopes, to active both Bcells and Tcells.

THE POINT: they induce cell-mediated AND humoral immunity
2 methods of making multivalent subunit vaccines:
1. Bind monoclonal antibodies to a solid matrix; saturate with Antigen. Administer via injection. No Tcell resp.

2. Add detergent to protein; forms ISCOMS, micells, and liposomes; these can cross the cell membrane and present by endogenous pathway; activates Tcells.
what is the purpose of the detergent in generating multivalent subunit vaccines like micelles and liposomes?
to extract protein antigens from cell membranes
How are liposomes generated?

What are they?
By mixing proteins up with lipids and detergent. Forms a bilayer with protein stuck in it, pointing out.
Difference between
Micells are plain protein that has reoriented itself with hydrophilic out.

Liposomes are protein stuck in lipid bilayer

ISCOMS are protein with lipids surrounding it to carry the protein.

All can cross cell membranes to be intracellular and activate CTLs.
How do DNA vaccines generate both humoral and cell-mediated responses?
Cell-mediated: expressed protein is processed by endogenous pathway, presented to Tc cells for CTLs.

Humoral: expressed protein is taken up by APCs with MHC2 and presented to Th and Bcells for humoral immune generation.
What vaccines are injected
Purified molecules
Inactivated vaccines
what vaccines do not induce Tc cell response?
Purified molecules, inactivated vaccine
Type of Antibody stimulated by:
Purified molecules
Protein, polysaccharide
Atten. vaccine
Inactiv. vaccine
Recombinant DNA
Polysacc: IgM; Protein: IgG (cl. sw.)
Atten: IgA
Inactiv: Consists of humoral - all
Recomb Vector: IgA
Multivalent: IgG
4 types vaccines that induce Tc Cells:
Multivalent subunit
Recomb Vector
What are the two unstable vaccines:
Recomb. dna
How do you administer Recomb Vector and Attenuated vacines?
Apply the natural environment
WHat is the safest vaccine?
Purified molecules; but it has the weakest response and requires boosters.
Downside of Atten vaccine:
side affects, can't give to immunosuppressed patients; reversion
Can you give a recombiant vector vaccine to an immunosuppressed?
no; requires their immune response to the vector-encoded antigen

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