Presented by

Resna N K
Ist sem M. Phil
 Immunity

 Active immunity

Resistance developed in response to stimulus by

an antigen (infecting agent or vaccine) and is
characterized by the production of antibodies by the
host.
 Passive immunity

Immunity conferred by an antibody produced in

another host. It may be acquired naturally or
artificially (through an antibody-containing
preparation).
 IMMUNITY
Specific defenses
Immunity

Active immunity Passive immunity

Following clinical infection natural Transfer of maternal

Antibodies Through placenta

Following subclinical infection Transfer of maternal

Antibodies Through milk
acquired
Following vaccination Following administration of
Immunoglobulin or antiserum
 Brief history of Immunization
• Edward Jenner demonstrated that inoculation
1796 with cowpox virus produced protection from
infection with smallpox.

• Louis Pasteur produced vaccines against

1860s-1890s
chickenpox,cholera, diphtheria, anthrax and rabies

Early 20th Century • Toxoid vaccines against diphtheria and tetanus

Post World War 2 successful live viral vaccines developed using cell
culture techniques
New technologies constantly developing:
Present and
future recombinant protein vaccines, DNA and conjugate
vaccines
 IMMUNIZATION

Passive Active

Natural- Artificial-
Injection of Inoculation with
Mother to foetus microbial pathogen
antibodies or
Previous infections vaccines
The CDC's recommended immunization schedule for the general
population
 Passive immunization
Introduced by Emil von Behring and Hidesaburo Kitasato
Serum
transferring
Infected animal Other animal

(get immunized)

Across the
Maternal antibodies Developing fetus
placenta

diphtheria, tetanus, streptococci, rubeola,

rubella, mumps, and poliovirus
 Maternal antibodies present in colostrum and milk

By injecting a recipient with preformed antibodies

Routinely administered to individuals exposed to botulism,

tetanus, diphtheria, hepatitis, measles, and rabies.

Does not activate the immune system, it generates no

memory response and the protection provided is transient.
 Active Immunization

Successfully eliminates the

A successful active Elicits a heightened pathogen or prevents
immunization immune response disease mediated by its
products.

Natural infection with a microorganism

Artificially by administration of a vaccine

important role in the reduction

of deaths from infectious
diseases, especially among
children
 Vaccination
Vaccination is a method of giving antigen to
stimulate the immune response through active
immunization.

A vaccine is an immuno-biological substance designed

to produce specific protection against a given disease.

A vaccine is “antigenic” but not “pathogenic”.

 Types of vaccines
Whole-Organism Vaccines

Attenuated vaccines
Purified Macromolecules as Vaccines
Capsular polysaccharide as vaccines
Inactivated exotoxins as vaccines

Recombinant microbial antigens as vaccines

Synthetic Peptides as Vaccines

Recombinant-Vector Vaccines
DNA vaccines
Multivalent subunit vaccines
 Whole-Organism Vaccines

 Many of the common vaccines currently in use

consist of inactivated (killed) or live but

attenuated (avirulent) bacterial cells or viral
particles.

 DNA vaccines that are currently being tested for

use in humans.
 Attenuated Viruses and Bacteria Cause
Immunity Without Disease

 Attenuated strains lose their ability to cause significant

disease (pathogenicity) but retain their capacity for
transient growth.

 Attenuation - achieved by growing a pathogenic

bacterium or virus for prolonged periods under abnormal
culture conditions.

 Example: an attenuated strain of

Mycobacterium bovis called
Bacillus Calmette-Guerin (BCG)
 Sabin polio vaccine

Consists of three attenuated strains of poliovirus, is administered

orally to children on a sugar cube or in sugar liquid.

In the intestines induces production of secretory IgA. The vaccine

also induces IgM and IgG classes of antibody.

The Sabin polio vaccine requires

boosters, because the three strains of
attenuated poliovirus in the vaccine
interfere with each other’s replication
in the intestine.
 Advantages
 Provide prolonged immune-system exposure to the
individual epitopes on the attenuated organisms,
resulting in increased immunogenicity and production of
memory cells.

 Often require only a single immunization, eliminating the

need for repeated boosters.

 The ability of many attenuated vaccines to replicate

within host cells makes them particularly suitable for
inducing a cell mediated response.
 Disadvantages
 There is the possibility that they will revert to a virulent
form.
 Reversion leads to subsequent paralytic disease.

 Attenuated vaccines also may be associated with

complications similar to those seen in the natural disease.

 A small percentage of recipients of the measles vaccine,

for example, develop post-vaccine encephalitis or other
complications.
 Inactivation by heat or chemicals

Chemicals
Inactivation Vaccine
of pathogen production
Heat

 Heat inactivation causes extensive denaturation of

proteins; thus, any epitopes present will altered
significantly.
 Chemical inactivation with formaldehyde or various
alkylating agents has been successful.
Salk polio vaccine
produced by formaldehyde
inactivation
Purified Macromolecules as Vaccines

Some of the risks associated with attenuated

or killed whole organism vaccines can be
avoided with vaccines that consist of specific,
purified macromolecules derived from
pathogens.

Three general forms of such vaccines are in

current use:
• Capsular polysaccharides
• Inactivated exotoxins,
• Recombinant microbial antigens
Capsular polysaccharide as vaccines

The virulence of some pathogenic bacteria depends

on the antiphagocytic properties of their
polysaccharide capsule.

Coating of the capsule with antibodies and/ or

complement greatly increases the ability of
macrophages and neutrophils to phagocytose such
pathogens.

These findings provide the rationale for vaccines

consisting of purified capsular polysaccharides.
• Eg: Vaccine for Streptococcus pneumoniae
• vaccine for Neisseria meningitidis
Cont…

 One limitation of polysaccharide vaccines is their inability

to activate TH cells.
 They activate B cells, resulting in IgM production but little
class switching, no affinity maturation, and little, if any,
development of memory cells.
 Inactivated exotoxins as vaccines

Some bacterial pathogens produce exotoxins.

Eg: diphtheria and tetanus

Purifying the bacterial exotoxin and then

inactivating the toxin with formaldehyde to
form a toxoid.

Vaccination with the toxoid induces anti-

toxoid antibodies, they binds to toxin and
neutralise it.
 Recombinant microbial antigens as vaccines

 The gene encoding any immunogenic

protein can be cloned and expressed in
bacterial, yeast, or mammalian cells using
recombinant DNA technology.
 A number of genes encoding surface
antigens from viral, bacterial, and protozoan
pathogens have been successfully cloned
into bacterial, yeast, insect, or mammalian
expression systems, and the expressed
antigens used for vaccine development.
 Hepatitis B vaccine is an example.
 This vaccine was developed by cloning
the gene for the major surface antigen of
hepatitis B virus (HBsAg) and expressing it in
yeast cells.
 Synthetic Peptides as Vaccines

 Peptides are not as immunogenic as proteins, and it is difficult

to elicit both humoral and cellular immunity to them.
 The use of conjugates and adjuvants can assist in raising
protective immunity to peptides advances in techniques to
produce recombinant proteins or fragments of proteins in
transfected cell culture have removed the impetus to develop
vaccines based on synthetic peptides.
 Construction of synthetic peptides for use as vaccines to
induce either humoral or cell-mediated immunity requires an
understanding of the nature of T-cell and B-cell epitopes.
 Ideally, vaccines for inducing humoral immunity should
include peptides that form immunodominant B-cell epitopes.
Recombinant-Vector Vaccines

Genes that encode major antigens of especially

virulent pathogens can be introduced into
attenuated viruses or bacteria.

The attenuated organism serves as a vector, replicating within

the host and expressing the gen product of the pathogen.

A number of organisms have been used for vector vaccines,

including vaccinia virus, the canary pox virus, attenuated
poliovirus, adenoviruses, attenuated strains of Salmonella, the
BCG strain of Mycobacterium bovis, and certain strains of
streptococcus
Production of vaccinia vector vaccine
Budr: bromodeoxy uridine
 DNA vaccines
Plasmid DNA encoding antigenic proteins is injected
directly into the muscle of the recipient.

Muscle cells take up the DNA and the encoded protein

antigen is expressed, leading to both a humoral antibody
response and a cell-mediated response.

The DNA appears either to integrate into the chromosomal DNA

or to be maintained for long periods in an episomal form.

One advantage is that,the encoded protein is expressed in

the host in its natural form—there is no denaturation or
modification.

DNA vaccines also induce both humoral and cell-

mediated immunity
 Multivalent subunit vaccines
Multivalent vaccines can present multiple copies of a
given peptide or a mixture of peptides to the immune
system.

One approach is to prepare solid matrix–antibody antigen (SMAA)

complexes by attaching monoclonal antibodies to particulate solid
matrices and then saturating the antibody with the desired antigen.

The resulting complexes are then used as

vaccines.

Another means of producing a multivalent vaccine is to use

detergent to incorporate protein antigens into protein micelles, lipid
vesicles (called liposomes), or immunostimulating complexes
(ISCOMs)
Cont…
 Membrane proteins from various pathogens, including
influenza virus, measles virus, hepatitis B virus, and HIV
have been incorporated into micelles, liposomes, and
ISCOMs and are currently being assessed as potential
vaccines.
 Liposomes and ISCOMs appear to fuse with the plasma
membrane to deliver the antigen intracellularly, where it
can be processed by the cytosolic pathway and thus
induce a cell-mediated response
(a) Solid matrix antibody-antigen
complexes can be designed to contain
synthetic peptides representing both T-cell
epitopes and B-cell epitopes.

(b) Protein micelles, liposomes, and

immunostimulating complexes (ISCOMs)
can all be prepared with extracted
antigens or antigenic peptides.
In micelles and liposomes, the hydrophilic
residues of the antigen molecules are
oriented outward.
In ISCOMs, the long fatty-acid tails of the
external detergent layer are adjacent to
the hydrophobic residues of the centrally
located antigen molecules.
(c) ISCOMs and liposomes can deliver
antigens inside cells, so they mimic
endogenous antigens. Subsequent
processing by the cytosolic pathway and
presentation with class I MHC molecules
induces a cell-mediated response.
 HAZARDS OF IMMUNIZATION

► No immune response is entirely free from the risk of

adverse reactions or remote squeal. The adverse
reactions that may occur may be grouped under the
following heads:

 Reactions inherent to inoculation

 Reactions due to faulty techniques
 Reactions due to hypersensitivity
 Neurological involvement
 Provocative reactions
 1. Reactions inherent to inoculation:

These may be local general reactions. The local reactions may

be pain, swelling, redness, tenderness and development of a
small nodule or sterile abscess at the site of injection.

The general reactions may be fever, malaise, headache and

other constitutional symptoms. Most killed bacterial vaccines
(e.g., typhoid) cause some local and general reactions.
Diphtheria and tetanus toxoids and live polio vaccine cause
little reaction.
 too much vaccine
given in one
dose,
faulty
improper route,
production of
vaccination
vaccine

2.Reactions vaccine or
contraindicatio due to
ns ignored dliluent
faulty contaminated
techniques

vaccine
prepared
wrong amount
incorrectly for
of diluent used
use

vaccine stored
incorrectly
3. Reactions due to hypersensitivity:
Viral vaccines symptoms may appear
prepared from within a few minutes of
embryonated eggs injection or may be
(e.g., influenza) delayed up to 2 hours
Various antibiotics
used in their
preparation
Anaphylaxis
Serum
sickness
Dangerous complication:
bronchospasm,
dyspnoea, pallor, Characterized by
hypotension and symptoms such as
collapse fever, rash, oedema
and joint pains
4. Neurological involvement:
 5. Provocative reactions:

 Occasionally following immunization there may occur a

disease totally unconnected with the immunizing agent
(e.g., provocative polio after DPT or DT administration
against diphtheria).
 The mechanism seems to be that the individual is
harboring the infectious agent and the administration
of the vaccine shortens the incubation period and
produces the disease or what may have been otherwise
only a latent infection is converted into a clinical attack.
Vaccine production