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QUESTIONS OF LECTURE

History of immunization Passive immunization Hypersensitivity reactions by injection of

the serum Monoclonal antibodies Immunoprophylaxis. Active immunization Adjuvants. Mechanism of action of

vaccines

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Milestones in immunizationMilestones in immunization

1500BC Turks introduce

variolation

3000BC Evidence of sniffing

powdered small pox crust in Egypt

2000BC Sniffing of small

pox crust in China

1700AD Introduction of

variolation in England

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Edward Jenner

Discovery of small pox vaccine (1780) Jenner replaced variolation by vaccination

(global eradication of the smallpox)

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Edward JennerAmong patients awaiting small pox vaccination

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1920sDiphtheria and Tetanus

1934Pertussis

1955Salk polio

Modern era of the vaccineModern era of the vaccine

1885Rabies vaccine (Pasteur)

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1960sMumps, measles and rubella virus

Sabin polio

1990s

Hepatitis and varicella

1985

Haemophilus

Modern era of the vaccineModern era of the vaccine

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Pre- & post-vaccine incidence of common preventable diseases

Pre- & post-vaccine incidence of common preventable diseases

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Different modes of acquiring immunity

Different modes of acquiring immunity

Natural resistance

Artificial Natural

Passive

Artificial Natural

Active

Immunity

Acquired

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Natural Artificial

Colostral transfer of IgA

Placental transfer of IgG

Antibodies or immunoglobulins

Immune cells

Passive ImmunityPassive Immunity

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 disease  indicationantibody source

Passive ImmunizationPassive Immunization

human, horsediphtheria, tetanus prophylaxis, therapy

varicella-zoster human immunodeficiencies

gas gangrene, botulism, snake bite, scorpion sting

horse post-exposure

rabies human post-exposure

hypogamma-globulinemia

human prophylaxis

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Advantages Disadvantages

serum sickness or anaphylaxis

immediate protection

no long term protection

risk of hepatitis and AIDS

Advantages and Disadvantages of Passive Immunization

Advantages and Disadvantages of Passive Immunization

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Hypersensitivity reactionsby injection of the serum

Anaphylactic shock Anaphylaxis (Gk. ana - away from, back

from; phylaxis - protection). Anaphylaxis is a form of altered reactivity, a state of the organism’s increased sensitivity induced by repeated injection of foreign proteins.

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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MONOCLONAL ANTIBODIES

A single antibody forming cell or clone produces antibodies specifically directed against a single antigen or antigenic determinant only. Such antibodies produced by a single clone and directed against a single antigenic determinant are called monoclonal antibodies (MA).

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Monoclonal Antibodies

ANTIGEN MYELOMA CELLS

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Active ImmunizationActive Immunization

Natural Artificial

exposure to sub-clinical infections

attenuated organisms

killed organisms

sub-cellular fragments

toxins

others

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Live Attenuated Vaccines

Live vaccines are used against a number of viral infections and some bacterial diseases. While live vaccines normally produce only self-limiting non-clinical infections and subsequent immunity, they carry a serious risk of causing overt disease in immunocompromised individuals.

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tuberculosis

polio*

measles, mumps & rubella

yellow feverMilitary and travelers

varicella zosterchildren with no history of chicken pox

hepatitis Anot required in SC

Live Attenuated VaccinesLive Attenuated Vaccines

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Killed Whole-Organism Vaccines

Killed (heat, chemical or UV irradiation) viral vaccines include those for polio (Salk vaccine), influenza, rabies, influenza, rabies, etc. Most bacterial vaccines are killed organisms (typhoid, cholera, plague, pertussis, etc.). Killed vaccines, as usually, are reactogenic and vaccines of limited effectiveness.

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influenzaelderly and at risk

typhoid, cholera, plagueepidemics and travelers

rabiespost exposure

pertussis

Killed Whole-Organism Vaccines

Killed Whole-Organism Vaccines

Q feverpopulation at risk

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Microbial Fragment VaccinesMicrobial Fragment Vaccines

Bordetella pertussisvirulence factor protein

Haemophilus influenzae Bprotein conjugated polysaccharide

Streptococcus pneumoniaepolysaccharide mixture

Neisseria meningitidispolysaccharide

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Microbial Fragment VaccinesMicrobial Fragment Vaccines

Clostridium tetani (tetanus)inactivated toxin (toxoid)

Corynebacterium diphtheriaeinactivated toxin (toxoid)

Vibrio choleraetoxin subunits

Hepatitis B viruscloned in yeast

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Toxoids

Toxoids are inactivated toxins that have lost their active site but have maintained their immunogenic determinants. Administration of the toxoid induces the production of antibodies capable of neutralizing the toxins by blocking their adsorption to cellular receptors.

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Modification of Toxin to ToxoidModification of Toxin to Toxoid

toxin moiety antigenic determinants

chemical

modification

Toxin Toxoid

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anti-Idiotype Vaccine

Immuno-dominant peptide

Future VaccinesFuture Vaccines

DNA

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Recommended Childhood Immunization Schedule

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Vaccines

The protective immunity conferred by a vaccine may be lifelong (measles, mumps, rubella, etc.) or may last as little as six months (cholera)

Vaccines can be used as immunotherapeutic agents. The use of vaccines to stimulate the immune system as therapy for chronic or latent infections (herpes, leprosy, tuberculosis)

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Active immunization may cause

fever, malaise and discomfort joint pains or arthritis (rubella) convulsions, sometimes fatal (pertussis) neurological disorders (influenza) allergies to eggs may develop as a

consequence of viral vaccines produced in eggs (measles, mumps, influenza, yellow fever).

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Adverse Events OccurringWithin 48 Hours DTP of Vaccination

Adverse Events OccurringWithin 48 Hours DTP of Vaccination

 Event  Frequencylocalredness, swelling, pain 1 in 2-3 doses

systemic: mild/moderatefever, drowsiness, fretfulness vomiting anorexia

1 in 2-3 doses

1 in 5-15 doses

systemic: more serious persistent crying, fevercollapse, convulsionsacute encephalopathypermanent neurological deficit

1 in 100-300 doses1 in 1750 doses1 in 100,000 doses1 in 300,000 doses

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ADJUVANTS

Adjuvant is a substance which enhances antigenic efficiency of vaccines. Adjuvant maintains the antigen in close proximity to immune cells and for keep the antigen from dissipating from the inoculation site.

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TYPES OF ADJUVANTS

Alum (aluminum hydroxide gels, which keep the antigen from dissolving away)

microorganisms (e.g. whole B. pertussis) Freund’s incomplete (antigen in an

emulsion of mineral oil and water) Freund’s complete (complete because it

adds mycobacterial antigens to the emulsion)

Liposomes

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Mechanism of action of vaccines

First, the lag or latent period is shorter Second, the ultimate level of antibody is

higher and persists longer than in the primary response

Third, there is more IgG than IgM in the antibody produced has occurred

Fourth, the amount of antigen is smaller than for the primary response

Finally, the antibody produced has a higher mean affinity in the secondary response

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