Aryssa Lagman; BMLS-3D
 Caused by the variola virus
Immunity
 Defined as the resistance to the disease, specifically
infectious diseases
Immune System
 The collection of cells, tissues, and molecules that mediate
resistance to infection
 The coordinated reaction of these cells & molecules to
infectious microbes
Immune System Includes
 Hematopoietic system (neutrophil, erythrocytes)
 Nervous system (fever/hypothalamus)
 Digestive system (stomach acid)
 Respiratory system (cilia, mucous, alveolar macrophage)
History
4 periods in the History of Immunity
1. Descriptive early period
2. Early attempts at immunization
3. Early experiments
4. Humoral vs. Cellular immunity
1) Descriptive Early Period
 Diseases were regarded as punishment from God
 Earliest written mention of the concept of immunity:
 Thucydides (plague of Athens in 430 BC)
2) Early Attempts at Immunization
 Mithradates VI
 Mithradates VI’s father (Anatolian King), was assassinated
by poisoning, said to be at his mother’s orders
 Mithradates was in competition with his brother for the
throne and his mother began to favor his brother
 Supposedly, during his youth, he began to suspect plots
against him at his own mother’s orders and was aware of
her possible connection with his father’s death.
 Mithradates VI took increasing daily doses of poisons from
the poisonous plants he ate with the thought that it might
make him stronger to survive any attempts to poison him
 Mithradatism is the practice of protecting oneself against
a poison by gradually self-administering non-lethal
amounts
 He then began to notice pains in his stomach during his
meals and suspected his mother had ordered small
amounts of poison to be added to his food to slowly kill
him off. With other assassination attempts, he fled into
the wild
 While there, and after his accession, he cultivated an
immunity to poisons by regularly ingesting sub-lethal
doses
 Indian Epics
 There was a practice of selecting beautiful girls and
administering poison in small amounts until they grew up,
thus making them insensitive to poison
 These maidens were called Visha Kanya (visha = poison,
kanya = maiden)
 It was believed that making love with vishakanyas can
result in death of their partners, hence they were
employed to kill enemies
 Immunization against Smallpox
 Virus enters the body through the lungs and is carried in
the blood to the internal organs and skin where it
multiplies
 Killed 10-30% of the world’s total population, the most
feared and greatest killer in human history
 Chinese
 Practiced inhalation of dried matter from pustules inserted
in nostrils
 Dried smallpox scabs were blown into the nose of an
individual who then contracted a mild form of the disease
(Asians and Africans)
 Europeans and their American cousins
 Tended to inoculate through a puncture in the skin
 Variolation
 Blowing dried scab material up the noses of the individuals
with a silver tube (“Gan Miao” : dry vaccine)
 Or using water to make a paste from scabs to insert into
the nostrils (“Shi Miao” : wet vaccine)
 Spread of Popularity in Europe: Variolation
 Early 18th Century: Lady Mary Wortley Montagu
inoculated her own children with smallpox virus
 “The Royal Experiment”
 Several prisoners and abandoned children were
inoculated by having the smallpox inserted under
the skin. Several months later, the homeless
children and prisoners were deliberately exposed
to smallpox
 When none contracted the disease, the procedure
was deemed safe and members of the royal family
were inoculated. Then 2 daughters of Prince &
Princess of Wales inoculated, hence became
popular
 Immunization against smallpox vaccination
 Edward Jenner
 Late 18th century
 Cowpox = Vaccinia virus
 Vacca is Latin for “cow”
 Hence for vaccination
 Edward Jenner inoculated James Phipps with cowpox
 Concept of “cross-reactivity”
 Epitopes of smallpox and cowpox are similar
 WHO:
 1978: all were vaccinated
 1980: total elimination of smallpox
3) Early Experiments
 19th Century: bacteria cause disease
 Robert Koch & Louis Pasteur established bacteria as cause
of disease
 Pasteur: injected animals with live attenuated
microorganisms  immunity versus chicken cholera
anthrax and rabies
  Subsequent experiments indicated that similar cells
existed in the blood of vertebrate animals and this led
Metchnikoff to propose that the cells are the ones that
responsible for this process (phagocytosis)
 Cellular Theory: Robert Koch
 A tuberculin reaction that occurs when a culture of
tubercle bacilli is injected into the skin of subjects already
infected with the disease. In humans a positive tuberculin
reaction indicates sensitization resulting from a
tuberculosis infection
 Used guinea pigs; if healthy: 10-14 days there will be
ulceration & necrosis

 Louis Pasteur on Anthrax and Rabies Vaccine

 Pasteur publicly claimed he had made the anthrax vaccine.
Skeptics challenged him to recreate the vaccine in a public
experiment
 Pasteur used 60 sheep: 10 control, 50 for testing
 25 sheep: vaccine, Anthrax virus, perfect
health
 25 sheep: no vaccine, Anthrax virus, died
 Pasteur produced the first vaccine for rabies by growing
the virus in rabbits, and then weakening it by drying the
affected nerve tissue  Humoral theory:
 On July 4, 1886, 9 year-old Joseph Meister was bitten  Paul Ehrlich
repeatedly by a rabid dog  Showed serum from immunized animals kills
 Pasteur treated him with his attenuated rabies vaccine bacteria
two days later. Meister survived.  Behring & Kitasato
 Attenuation:  Immunity to diptheriae & tetanus due to
 Change in the virulence of a pathogenic antibodies to the toxins
microorganism (weakened but viable strain)  Passive transfer of immune serum  protection = 1st
 Induced by passage through another hose immunotherapy
species  War of the Cells and Antibodies: Truce
 Decreased virulence for the native host  Sir Almoth Wright & Douglas
 Basis for the development of live vaccines  Opsonization of bacteria by antibodies
 Difference between Jenner’s and Pasteur’s concepts on  Attempted fusion of Cellular and Humoral
vaccination Theories—“Sir Almost Right”
 Edward Jenner = Cross Reactivity  Encapsulated
 The ability of an individual Ab combining site to o Opsonization  complement,
react with more than one antigenic determinant phagocytes, antibodies
 The ability of a population of Ab molecules to
react with more than one Ag

 Nonencapsulated
 Louis Pasteur = Live-attenuated vaccines
 Wild virus replication in unfavorable conditions Scientist Discovery
 The process is repeated many times Bordet Complement system
 To produce an attenuated strain, unable to Salk, Sabin Polio vaccine
Reed Yellow fever vaccine
cause disease
Frazer Human papillomavirus
4) Wars on cells and antibodies vaccine
Burnet Clonal selection theory
A. Cellular Theory: Kohler Monoclonal antibodies
Tonegawa Antibody diversity
 Ellie Metchnikoff Snell, Benacerraf, Dausset Major Histocompatibility
 Robert Koch Complex; Transplant
rejection
B. Humoral Theory:
Lessons:
 Paul Ehrlich
 Does not happen overnight
 Behring & Kitasato
 Needs combined efforts
 It is ever changing
 Cellular Theory: Ellie Metchnikoff
 Experiments often crude and used a lot of animal testing
 Metchnikoff discovered that the transparent starfish larva
methods
contained cells that could efficiently surround and ingest
foreign material, including microorganisms.  Risks were necessary