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 4
Principles and Effects of Vaccination
Sterile protection Non sterile protection Specific Specific Quick amplification Pathogen neutralization Specific Clearance of the pathogen before spreading Extra cellular pathogens or free intracellular pathogens Antibody mediated Clearance of the pathogen after infection Intracellular pathogen with cell to cell transmission Cell mediated
Types of Vaccines and Their Characteristics
Vaccine technologies
•Live vaccines •Recombinant vaccines •Killed vaccines •Plasma derived vaccines •Polysaccharide conjugates •Peptide vaccines •Subunit vaccines •DNA vaccines •Combination vaccines •Passive (antibodies)
Examples
polio, yellow fever RSV influenza, pertussis Hepatitis B Hib, Pneumo Malaria HIV candidates Influenza DPT 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 secondary (booster) immunizations.
as a series of
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
of Clostridiun tetani
Tetanus Toxoid
chemical and temperature modification
toxin moiety antigenic determinants
15
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
Examples
Combination vaccines
influenza trivalent OPV, inactivated IPV DPT, DPT/Hib, etc. MMR, MMRV PnC/MnC Advantages: Disadvantages: only one needle at a visit may reduce number of visits reduces costs of administration geographic tailoring 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 Guerin.
Calmette
Used
and 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.
sensibillization It has high 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
Neisseria meningitidis
of group A and C.
Appointment:
Prophylaxis of cerebrospinal caused meningitis, meningococcus of serogroupp Vaccination A and C.
is recommended in endemic regions, and also in the case of epidemic, caused meningococcus serogorupp A or C.
of
What type of immunity (originally) is created in an organism after introduction?
Postvaccine Active Humoral Antibacterial General Specific
Staphylococcal
Content:
toxoid
this vaccine, in which contains inactivated, which help formalin temperature (0,4%) and (56°C) exotoxin
S.aureus
. It is used for specific preventive and treatment of infections staphylococcal
What type of immunity (originally) is created in an organism after introduction?
Postvaccine Active Humoral Antitoxic General Specific
APDT
Content:
-
аdsorbed on the hydrate aluminium of oxide of mixed vaccine, the consisting microorganisms of killed – 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
– (gamma globulin) 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
reduce the pathogen load prevent contacts with host cell 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 gamma globulins fraction of serum of the animals.
diminished hyperimmunized There is the 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 heterogenic introduction serum, eliminate development anaphylactic serum illness.
shock of to of and
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 immunized.
volunteers, have been
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 meaning protection. Anaphylaxis is an inclusive term for the reactions caused when certain antigens combine with IgE antibodies.
ana-, meaning against, and the Greek phylaxis, • 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 37
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 administration of heterogeneous serums.
the
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 introduction of the antigen.
after re-