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PHAR 532
LECTURE 14
IMMUNOTHERAPY
Antimicrobial agents and
Immunization
Immunotherapy
Definition: treatment that is designed to harness the
ability of the body’s immune system to combat
infection or disease.
Types: Active, Passive
Active immunotherapy It is the type
of immunotherapy that attempts to stiumlate the
host intrensic immune response to a disease
Specific active immunotherapy
Non specific active immunotherapy
Specific active immunotherapy: The generation of
cell mediated and antibody immune responses
focused on specific antigen. Eg. cancer vaccines.
Non specific immunotherapy the generation of
general immune system response using cytokines.
Passive immunotherapy: Administration of
antibodies to fight specific disease.
Effective immunotherapy
Optimization of interaction between antigenic
peptide, antigen presenting cells, and T cells.
Simultaneous blockade of negative regulatory
mechanisms,
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
Vaccination
Types of Vaccines and Their
Characteristics
Types of vaccines
Attenuated vaccines
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 of
95% 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
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 vaccines
Toxoids: inactivated toxins. 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.
Toxoids
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.
Subunit and recombinant
Conjugated vaccines have been developed in
recent years to deal with the poor immune response of
children to vaccines based on capsular polysaccharides.
Conjugated vaccines
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
Sources of Passive Immunity
Almost all blood or blood products
Homologous pooled human antibody (immune
globulin)
Homologous human hyperimmune globulin
Heterologous hyperimmune serum (antitoxin)
Serum preparations classification
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 heterogeneous serum
Anaphylactic shock: Type I, or anaphylactic, reactions
often occur within 2 to 30 minutes after a person
sensitized to an antigen is re-exposed to that antigen.
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
Cancer vaccines
Identification of tumor rejection antigens by
defining tumor-associated antigens that stimulate T-
cell responses.
Tumor Antigens:
Product of mutated genes
Consequence of enhanced or aberrant expression
Product of oncogenic viruses
Oncofetal antigens
Altered cell surface glycolipids and glycoproteins
Differentiation antigens
Mechanism of T cell response
Other approaches
Monoclonal antibodies may also be covalently coupled to
drugs, toxins, or radiochemicals – the antibody serves as
guided missile that delivers a therapeutic warhead to
cancers expressing particular surface antigens
Anti-CD30 antibodies: – CD30 is a member of the TNF
receptor family of transmembrane proteins that is
expressed by particular T cell lymphomas and most
Hodgkin lymphomas. – Antibodies against CD30 linked
to a cytotoxic drug have recently produced remarkable
responses in patients with CD30-positive lymphomas
that have failed conventional therapies
The 3 “E”s

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Antimicrobial agents and immunization immunotherapy

  • 2. Immunotherapy Definition: treatment that is designed to harness the ability of the body’s immune system to combat infection or disease. Types: Active, Passive Active immunotherapy It is the type of immunotherapy that attempts to stiumlate the host intrensic immune response to a disease Specific active immunotherapy Non specific active immunotherapy
  • 3. Specific active immunotherapy: The generation of cell mediated and antibody immune responses focused on specific antigen. Eg. cancer vaccines. Non specific immunotherapy the generation of general immune system response using cytokines. Passive immunotherapy: Administration of antibodies to fight specific disease.
  • 4. Effective immunotherapy Optimization of interaction between antigenic peptide, antigen presenting cells, and T cells. Simultaneous blockade of negative regulatory mechanisms,
  • 5. Passive Immunization A preparation of antibodies that neutralizes a pathogen and is administered before or around the time of known or potential exposure
  • 6. Vaccines Provide an antigenic stimulus that does not cause disease but can produce long lasting, protective immunity
  • 8. Types of Vaccines and Their Characteristics
  • 10. Attenuated vaccines 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 of 95% 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.
  • 11. 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
  • 12. 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 vaccines
  • 13. Toxoids: inactivated toxins. 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. Toxoids
  • 14. 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. Subunit and recombinant
  • 15. Conjugated vaccines have been developed in recent years to deal with the poor immune response of children to vaccines based on capsular polysaccharides. Conjugated vaccines
  • 16. 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
  • 17. Sources of Passive Immunity Almost all blood or blood products Homologous pooled human antibody (immune globulin) Homologous human hyperimmune globulin Heterologous hyperimmune serum (antitoxin)
  • 18. Serum preparations classification homogeneous serum: serum obtained from blood donor volunteers, have been immunized. heterogeneous serum: serum obtained from blood of animals hyperimmunized.
  • 19. Hypersensitivity reactions by injection of heterogeneous serum Anaphylactic shock: Type I, or anaphylactic, reactions often occur within 2 to 30 minutes after a person sensitized to an antigen is re-exposed to that antigen. 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
  • 20. Cancer vaccines Identification of tumor rejection antigens by defining tumor-associated antigens that stimulate T- cell responses.
  • 21. Tumor Antigens: Product of mutated genes Consequence of enhanced or aberrant expression Product of oncogenic viruses Oncofetal antigens Altered cell surface glycolipids and glycoproteins Differentiation antigens
  • 22. Mechanism of T cell response
  • 23. Other approaches Monoclonal antibodies may also be covalently coupled to drugs, toxins, or radiochemicals – the antibody serves as guided missile that delivers a therapeutic warhead to cancers expressing particular surface antigens Anti-CD30 antibodies: – CD30 is a member of the TNF receptor family of transmembrane proteins that is expressed by particular T cell lymphomas and most Hodgkin lymphomas. – Antibodies against CD30 linked to a cytotoxic drug have recently produced remarkable responses in patients with CD30-positive lymphomas that have failed conventional therapies