Transcript Immunotherapy and Prevention

Sumy State University
The Department of Infectious Diseases and Epidemiology
with Course of Microbiology, Virology and Immunology
Immunotherapy
and Prevention
Tatyana Ivakhnyuk
2011
Active Immunization
Stimulates the host’s immune system to
produce specific antibodies or cellular
immune responses or both which
would protect against or eliminate a
disease.
Passive Immunization
A preparation of antibodies that
neutralizes
a pathogen and is
administered before or around the
time of known or potential exposure.
Vaccines
Provide an antigenic
stimulus that does not
cause disease but can
produce long lasting,
protective immunity
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Principles and Effects of
Vaccination
Sterile protection
Specific
Non sterile protection
Specific
Quick
amplification
Pathogen
neutralization
Clearance of the pathogen
before spreading
Specific
Clearance of the pathogen
after infection
Extra cellular
pathogens or free
intracellular pathogens
Intracellular pathogen
with cell to cell
transmission
Antibody mediated
Cell mediated
Types of Vaccines and Their
Characteristics
Vaccine technologies
•Live vaccines
•Recombinant vaccines
Examples
polio, yellow fever
RSV
•Killed vaccines
•Plasma derived vaccines
•Polysaccharide conjugates
•Peptide vaccines
•Subunit vaccines
•DNA vaccines
influenza, pertussis
Hepatitis B
Hib, Pneumo
Malaria
HIV candidates
Influenza
•Combination vaccines
DPT
•Passive (antibodies)
e.g. HBIG, VZIG
Types of Vaccines and Their Characteristics
• Attenuated whole-agent vaccines
use living but attenuated (weakened) microbes. Live
vaccines more closely mimic an actual infection.
Lifelong immunity, especially with viruses, is
often achieved without booster immunizations, and
an effectiveness rate of95% is not unusual. This
long-term effectiveness probably occurs because the
attenuated viruses replicate in the body, increasing
the original dose and acting as a series of
secondary (booster) immunizations.
Attenuated whole-agent vaccines
Ideal properties of a live vaccine
Attenuated microorganism which replicates
in the host thus eliciting immune responses
similar to natural infection
Able to elicit lifelong protection using only
one or two doses
Disease causing capacity is virtually eliminated.
Elicits both humoral and cellular immunity
Examples of Attenuated or live vaccines
Live attenuated vaccines
oral polio, yellow fever
mumps, measles, VZV
tuberculosis (BCG)
Types of Vaccines and Their Characteristics
Inactivated
whole-agent
vaccines
use microbes that have been killed, usually by formalin or
phenol. Inactivated virus vaccines used in humans include
those against rabies (animals sometimes receive a live
vaccine considered too hazardous for humans), influenza,
and polio (the Salk poliovaccine). Inactivated bacterial
vaccines include those for pneumococcal pneumonia and
cholera. Several long-used inactivated vaccines that are being
replaced for most uses by newer, more effective types are
those for pertussis (whooping cough) and typhoid.
Inactivated whole-agent vaccines
Types of Vaccines and Their Characteristics
• Toxoids, which
are inactivated toxins, are
vaccines directed at the toxins produced by a
pathogen. The tetanus and diphtheria toxoids
have long been part of the standard childhood
immunization series. They require a series of
injections for full immunity, followed by boosters
every 10 years. Many older adults have not
received boosters; they are likely to have low levels
of protection.
Modification of Toxin
to Toxoid (example)
Extracellular Toxin
Toxin tetani
of Clostridiun
Tetanus Toxoid
chemical and temperature
modification
toxin moiety
antigenic determinants
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Types of Vaccines and Their Characteristics
Subunit vaccines
use only those antigenic
fragments of a microorganism that best stimulate an immune
response. Subunit vaccines that are produced by genetic
modification techniques, meaning that other microbes are
programmed to produce the desired antigenic fraction, are
called recombinant vaccines.
For example, the vaccine against the hepatitis B virus
consists of a portion of the viral protein coat that is
produced by a genetically modified yeast.
Types of Vaccines and Their Characteristics
Conjugated vaccines
have been developed
in recent years to deal with the poor immune response of
children to vaccines based on capsular polysaccharides.
Polysaccharide vaccines
Unique type of inactivated subunit vaccine
composed of long chains of sugar molecules
that make up the surface capsule of
certain bacteria.
Available for Pneumococcal disease,
meningococcal disease and
Haemophilus influenzae type b
Combination vaccines
Examples
influenza
trivalent OPV, inactivated IPV
DPT, DPT/Hib, etc.
MMR, MMRV
PnC/MnC
Advantages:
only one needle at a visit
may reduce number of visits
reduces costs of administration
geographic tailoring
Disadvantages:
loss of immunogenicity due to competition
technically more difficult to produce
higher production costs
higher evaluation costs
Correlates ?
• Humoral component
– Tetanus
– Dyphteria
– H. influenzae
– Influenza
– Measles
– Varicella (herpes
zoster)
– Dengue
– S. pneumoniae
• Cellular components
– BCG
– HIV
– Herpes type 1&2
– Shingles (herpes zoster)
– Influenza in elderly
– Varicella (herpes
zoster)
– Measles
Description of immunity
Postinfection
Postvaccine
Active
Passive
Humoral
Cellular
Antibacterial
Antiviruses
Antitoxins
Antifungal
Specific
Nonspecific
Group specific, species specific,
Type-specific
BCG (bacillus Calmette-Guerin)
• Content:–
living
or
attenuated, liophilic dried up
culture unpathogenic strain
of M. tuberculosis, was
found by the French
scientists
Calmette
and
Guerin. Used for the active
specific
prophylaxis
of
tuberculosis. Plugged in the
calendar of inoculations.
Contra-indicated people with
violation of cellular link of
immunity.
What type of immunity
(originally) is created in an
organism after introduction?
Postvaccine
Active
Cellular
Antibacterial
General
Specific
Killed brucellosis vaccine
• Content:– It contains the killed by
heat the cow-type and sheep-type
species of the brucella. It is using
for immunotherapy by chronic
brucellosis.
It
has
high
sensibillization and allergic ability
and it is using only for patients with
normegric reaction of the organism
on the intra-skin injection of the
brucellin. For the patients with
hyperergia and allergic reaction and
for
person
with
generalized
infection
the
vaccination
is
dangerous. The intra-skin therapy is
making often then intravenous. The
injection of the brucellin is useful
for same patients.
What type of immunity
(originally) is created in
an organism after
introduction?
Postvaccine
Active
Cellular
Antibacterial
General
Specific
Meningococcal chemical vaccine
Content: This vaccine contains
cleared polysaccharide of
Neisseria meningitidis group
A and C.
Appointment: Prophylaxis of
cerebrospinal
meningitis,
caused meningococcus of
serogroupp A and C.
Vaccination
is
recommended in endemic
regions, and also in the case
of
epidemic,
caused
meningococcus
of
serogorupp A or C.
What type of immunity (originally)
is created in an organism after
introduction?
Postvaccine
Active
Humoral
Antibacterial
General
Specific
Staphylococcal
toxoid
Content: this vaccine, in
which
contains
inactivated, which help
formalin (0,4%) and
temperature
(56°C)
exotoxin S.aureus. It is
used
for
specific
preventive and treatment
of
staphylococcal
infections
What type of immunity (originally)
is created in an organism after
introduction?
Postvaccine
Active
Humoral
Antitoxic
General
Specific
APDT
Content: - аdsorbed on the
hydrate of oxide of
aluminium
mixed
vaccine, consisting of
the
killed
microorganisms – the
whooping-cough
bacteria’s and toxoids –
diphtherial and tetanic.
Used
for
plannad
prophylaxis.
What type of immunity (originally)
is created in an organism after
introduction?
Postvaccine
Active
Humoral
Antitoxic
Antibacterial
General
Specific
Adjuvant activity
•Formation of a depot of antigen primarily at the
site of application from which the antigen is
released during a variable period
•Increased uptake of antigen into APCs
•Induction of synthesis and secretion of
enhancing factors, such as cytokines.
Adjuvant activity
•
•
•
•
•
Facilitation of antigen transport, uptake and
presentation by antigen-capturing and processing cells
Repeated or prolonged release of antigen (depot effect)
Signaling of receptors activating innate immune cells to
release cytokines which upregulate co-stimulatory
molecules
‘Danger signals’ from stressed or damaged tissues
activate APCs
Signaling by recombinant cytokines or co-stimulatory
molecules mimics classical adjuvant activity
Immunotherapy – preformed Ab
Immune serum globulin – (gammaglobulin) contains immunoglobulin
extracted from the pooled blood of at
least 1,000 human donors
• Treatment of choice for preventing
measles, hepatitis A and replacing Ab in
the immune deficient
• Lasts 2-3 months
Immunotherapy – preformed Ab
Specific immune globulin- prepared from
•
•
•
•
convalescent patients in a hyperimmune state
Contains high titer of specific Ab
pertussis, tetanus, chickenpox, hepatitis B
sera produced in horses are available for
diphtheria, botulism, spider and snake bites
act immediately and can protect patients for
whom no other useful medication exists
Effectors functions of antibodies
• Neutralization
prevent contacts with host cell
reduce the pathogen load
Cell
Inhibit bacterial toxins
• Complement mediated lyses
inhibits the pathogen
penetration of the host cell
Complement binding  pathogen destruction
Antianthracis gamma-globulin
• Content: preparation contains
antitoxins. It is gammaglobulins fraction of serum
of the hyperimmunized
animals. There is the
diminished
amount of
ballast matters in such
preparation, that diminishes
probability of development
of by-reactions, above all
things allergic substantially
What type of immunity
(originally) is created in
an organism after
introduction?
Passive
Humoral
Antibacterial
General
Specific
Antidiphtherial antitoxic serum
• Content: preparation is got
by hyperimmunization of
horse a diphtherial toxoid.
Effective mean of specific
therapy of diphtheria. At the
use it should be remembered
rules of introduction of
heterogenic
serum,
to
eliminate development of
anaphylactic shock and
serum illness.
What type of immunity
(originally) is created in
an organism after
introduction?
Passive
Humoral
Antibacterial
General
Specific
Sources of Passive Immunity
• Almost all blood or blood products
• Homologous pooled human antibody
(immune globulin)
• Homologous human hyperimmune globulin
• Heterologous hyperimmune serum
(antitoxin)
Classification the serum preparations
• homogeneous serum: serum obtained from
blood donor volunteers, have been
immunized.
• heterogeneous serum: serum obtained from
blood of animals hyperimmunized.
Hypersensitivity reactions
by injection of the heterogeneous serum
• Anaphylactic shock
Type I, or anaphylactic, react ions often occur within 2 to 30
minutes after a person sensitized to an antigen is reexposed
to that antigen. Anaphylaxis means opposite of protected," from
the prefix ana-, meaning against, and the Greek phylaxis,
meaning protection. Anaphylaxis is an inclusive term for the
reactions caused when certain antigens combine with IgE
antibodies.
Anaphylactic responses can be systemic reactions, which produce
shock and breathing difficulties and are sometimes fatal, or
localized reactions, which include common allergic conditions
such as hay fever, asthma, and hives (slightly raised, often
itchy and reddened areas of the skin).
• Serum Sickness
This is a systemic form of hypersensitivity of immediate reaction. It appears 7 to
12 days following single injection of high concentration of foreign serum
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The mechanism of anaphylaxis
IgE antibodies, produced in response to an antigen
(heterogenic antibody), coat mast cells and basophils. When an
antigen bridges the gap between two adjacent antibody
molecules of the same specificity,
the cell under goes
degranulation and releases histamine and other mediators.
Bezredka method
• Bezredka method (A.M. Bezredka, a
microbiologist, was born in Russia, worked
in France, 1870-1940) - a specific method
of desensitization of the body that is used to
prevent
complications
after
the
administration of heterogeneous serums.
Bezredka method
Heterologous
hyperimmune
sera
(eg,
antibotulinum, antitetanus, etc.) are highly
concentrated; for desensitization recommended
minimum dose. While under the influence of
serum antigen occurs, neutralizing antibodies,
fixed on the cell surface, and a decline in blood
concentrations of physiologically active
substances (histamine, etc.) that prevents the
development of complications after reintroduction of the antigen.
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