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Sumy State University . The D epartment of I nfectious D iseases and E pidemiology with C ourse of M icrobiology, V irology and I mmunology . Immunotherapy and Prevention . T a t y ana Ivakhnyuk 2011. Active Immunization.

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Immunotherapy and prevention

Sumy State University

The Department of Infectious Diseases andEpidemiology with Course of Microbiology, Virology and Immunology

Immunotherapy and Prevention

Tatyana Ivakhnyuk

2011


Active immunization
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
Vaccines

Provide an antigenic stimulus that does not cause disease but can produce long lasting, protective immunity


Principles and effects of vaccination

Sterile protection

Non sterile protection

Specific

Specific

Quick

amplification

Pathogen

neutralization

Specific

Clearance of the pathogen

before spreading

Clearance of the pathogen

after infection

Extra cellular pathogens or free intracellular pathogens

Antibody mediated

Intracellular pathogen with cell to cell transmission

Cell mediated

Principles and Effects of Vaccination



Vaccine technologies

  • Examples

  • Live vaccines polio, yellow fever

  • Recombinant vaccines RSV

  • Killed vaccines influenza, pertussis

  • Plasma derived vaccines Hepatitis B

  • Polysaccharide conjugates Hib, Pneumo

  • Peptide vaccines Malaria

  • Subunit vaccines HIV candidates

  • DNA vaccines Influenza

  • Combination vaccines DPT

  • Passive (antibodies) e.g. HBIG, VZIG


  • Types of vaccines and their characteristics1
    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.



    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 characteristics2
    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.



    Types of vaccines and their characteristics3
    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

    Tetanus Toxoid

    chemical and temperature

    modification

    toxin moiety

    antigenic determinants

    Modification of Toxin to Toxoid (example)

    Extracellular Toxin

    of Clostridiun tetani

    Toxin


    Types of vaccines and their characteristics4
    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 characteristics5
    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

    Correlates ?


    Description of immunity
    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
    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.

    Whattypeofimmunity (originally) iscreatedinanorganismafterintroduction?

    Postvaccine

    Active

    Cellular

    Antibacterial

    General

    Specific


    Killed brucellosis vaccine
    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.

    Whattypeofimmunity (originally) iscreatedinanorganismafterintroduction?

    Postvaccine

    Active

    Cellular

    Antibacterial

    General

    Specific


    Meningococcal chemical vaccine
    Meningococcal chemical vaccine

    Content:This vaccine contains cleared polysaccharide of Neisseriameningitidis 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.

    Whattypeofimmunity (originally) iscreatedinanorganismafterintroduction?

    Postvaccine

    Active

    Humoral

    Antibacterial

    General

    Specific


    Staphylococcal toxoid
    Staphylococcal toxoid

    Content: this vaccine, in which contains inactivated, which help formalin (0,4%) and temperature (56°C) exotoxinS.aureus. It is used for specific preventive and treatment of staphylococcal infections

    Whattypeofimmunity (originally) iscreatedinanorganismafterintroduction?

    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.

    Whattypeofimmunity (originally) iscreatedinanorganismafterintroduction?

    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
    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 ab1
    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

    Cell

    Effectors functions of antibodies

    prevent contacts with host cell

    • Neutralization

    • Complement mediated lyses

    reduce the pathogen load

    Inhibit bacterial toxins

    inhibits the pathogen

    penetration of the host cell

    • Complement binding è pathogen destruction


    Antianthracis gamma globulin
    Antianthracis gamma-globulin

    • Content:preparation contains antitoxins. It is gamma-globulins 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

    Whattypeofimmunity (originally) iscreatedinanorganismafterintroduction?

    Passive

    Humoral

    Antibacterial

    General

    Specific


    Antidiphtherial antitoxic serum
    Antidiphtherial antitoxic serum

    • Content:preparation is got by hyperimmunization of horse a diphtherialtoxoid. 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.

    Whattypeofimmunity (originally) iscreatedinanorganismafterintroduction?

    Passive

    Humoral

    Antibacterial

    General

    Specific


    Sources of passive immunity
    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
    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
    Hypersensitivity reactionsby 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


    The mechanism of anaphylaxis
    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

    • 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 method1
    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 re-introduction of the antigen.


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