Explain the historical background behind Immunology

1. IMMUNOLOGY – A HISTORICAL PERSPECTIVE
Dr. Valli Syam

2. Immunity – ‘immunis’ (L) - “exempt” –
Military terminology – Conscription
 State of protection from infectious disease
Thucydides, the great historian of the Peloponnesian War.
430 BC - Describing a plague in Athens – only those who had
recovered from the plague could nurse the sick because they would not
contract the disease a second time.
It took nearly two thousand years to transform this concept as a new
medically effective practice

3. Chinese and Turks in the fifteenth century –
The dried crusts derived from smallpox pustules
- inhaled into the nostrils or
- inserted into small cuts in the skin (a technique called variolation).
1718, Lady Mary Wortley Montagu, the wife of the British ambassador to
Constantinople, had the technique performed on her own children.

4. Benjamin Jesty (Farmer in Yetminster, England) (1774)
The notion that those people infected with cowpox (Vaccinia),
a relatively mild disease, were subsequently protected against smallpox
– common observation with country folk in the late 18th century
The milkmaids and other workers who contracted cowpox – immune to smallpox - nurse
smallpox victims without fear of contracting the disease
Jesty was one of the first to intentionally administer the less virulent virus.
To protect his family from small pox, Jesty decided to try to give his wife Elizabeth and
two eldest sons immunity by infecting them with cowpox
Using a darning needle, transferred pustular material to them from the cow by
scratching their arms.
The boys had mild local reactions and quickly recovered
but his wife's arm became very inflamed and she too recovered fully in time.

5. English physician Edward Jenner, in 1798.
- milkmaids who had contracted the mild disease
cowpox (caused by Vaccinia) were subsequently
immune to smallpox (caused by Variola),
a disfiguring and often fatal disease
- Introducing fluid from a cowpox pustule into people (i.e., inoculating them)
might protect them from smallpox.
- Inoculated an eight-year-old boy with fluid from a cowpox pustule and later
intentionally infected the child with smallpox.
As predicted, the child did not develop smallpox.
Jenner’s technique of inoculating with cowpox to protect against smallpox spread
quickly throughout Europe.
This techniques was not applied to other diseases – reasons
 Lack of obvious disease target
 Knowledge of their causes

6. Louis Pasteur – French Chemist and Microbiologist (1882-1895)
• Worked with fermentation process
• Suggested specific microorganisms were involved in Fermentation and putrefaction –
Direct support for Germ Theory of Diseases
• Worked in wine and beer industry – Pasteurization – heated wine to 50-600C
• Fermentation and putrefaction were often perceived as being spontaneous
phenomena, a perception stemming from the ancient belief that life could generate
spontaneously (Disapproved Spontaneous generation)
• The medical establishment was reluctant to accept his germ theory of disease,
primarily because it originated from a chemist.
• However, during the next decade, Pasteur developed the overall principle of
vaccination and contributed to the foundation of immunology

7. Inject with Fresh
Culture of Chicken
cholera
Old culture of Chicken
cholera
Inject Chicken
Chicken died due to
cholera
Chicken fell ill but did
not die due to cholera
Inject Chicken
Culture of Chicken
cholera
Fresh lot of Chicken
Chicken died due to
cholera
Chicken were hale
and healthy
Pasteur hypothesized that aging had weakened the virulence of the pathogen
He called this attenuated strain a vaccine [Vacca (L) – Cow] – Honour to Jenner work
Pasteur
experiment
with
Fowl
cholera
(1880)

8. • Pasteur then became interested in the
prevention of anthrax, a widely spread plague of cattle
• In 1874, a rural physician, Robert Koch (1843-1910),
- demonstrated the role of Bacillus anthracis in this disease,
- and succeeded in preserving its pathogenicity after eight subcultures.
• He also discovered the resistant spores of this bacterium.
• Pasteur confirmed its causative role by subculturing this bacterium one
hundred times, without altering the high virulence of the pathogen.
• Then, he tried in 1881 to attenuate its virulence by preventing spore
formation.
• This was achieved by maintaining live bacilli in the presence of oxygen.
• In optimal conditions, live bacilli were grown for 8 days in ventilated culture
broth incubated at 42-43°C.
• Bacilli progressively lose their virulence, becoming harmless in animals, such
as rabbits, sheep and guinea-pigs.

9. The protocol of vaccination
Cattle selected 24 Sheeps 1 Goat 6 Cows
(Experimental group vaccinated)
May 5, 1881 All animals vaccinated with 5 drops of living attenuated
B.anthracis
May 17, 1881 All animals injected with less attenuated B. anthracis
May 31, 1881 All animals injected with virulent B. anthracis
In addition
24 Sheeps 1 Goat 3 Cows
(Control group – non vaccinated)
These animals injected with virulent B. anthracis
June 2, 1881 All non vaccinated animals – died –
Only 2 sheeps of protected group succumbed
– 1 pregnancy complication

10. Pasteur experiment – Rabies vaccine
Rabies causing organism was
Isolated from Fox (Canine Natural host)
Unlike Cholera and Anthrax, this is caused by virus –
quick replication & high mutation rate
By serial passages of a virus through a different species, the virus becomes
more adapted to that species and less adapted to its original host
Injected Rabbit – Unnatural host
Isolated from this Rabbit and injected into New Rabbit
Taken the spinal cord and dried

11. 1st human trial 6th July 1885
9 year old boy – Joseph Meister – mauled by rabid dog
Next 11 days – 13 inoculations –
each week with viruses weakened for shorter period of time
Three months later Joseph Meister was in good health
He lived and later became a custodian at the Pasteur Institute
In 1886 – around 350 people were treated
Pasteur experiment – Rabies vaccine

12. Elie Metchnikoff
In 1882 – Inserted small citrus thorns into starfish larvae,
Found unusual cells surrounding the thorns
In animals which have blood, the white blood cells gather at the
site of inflammation
He hypothesized that this could be the process by which bacteria were attacked and
killed by the white blood cells – Carl Friedrich Wilhelm Claus, Professor of Zoology at
the University of Vienna suggested to him the term “Phagocyte" for a cell which can
surround and kill pathogens.

13. Emil von Behring and Shibasaburo Kitasato
(1890)
Emil von Behring – Nobel prize
Presence of antitoxin in blood indicating
recovery from diphtheria
serum from animals previously immunized to
diphtheria could transfer the immune state to
unimmunized animals
Von Behring first to use Antiserum in treating
Active diseases
Roux & Yersin
(1889)
Isolated Diphtheria Toxin

14. Paul Ehrlich –
presented chemical theory to explain the formation of antitoxins, or antibodies, to fight
the toxins released by the bacteria
recognized that a specific antigen elicited the production of a specific antibody
Ehrlich hypothesized that these antibodies were specialized molecular structures with specific
receptor sites that fit each pathogen like a lock and key.
Merill Chase –
Merrill Wallace Chase brought an end to the early-20th-century belief that antibodies alone
protected the body from allergies and disease-causing pathogens.
Led to the identification of B cells, T cells, dendritic cells, and other types of white blood cells as
the body’s central safeguards against infection.
1940 - Transferred immunity to Tuberculosis organism by transferring WBC between Guinea pigs
Merill Chase and Paul Ehrlich – 1908 Nobel Prize in Physiology or Medicine

15. French and Germans dominated 2 schools of thought
Humoralist – Humoral Antibody – Pioneer Paul Ehrlich – Emil Von Behring
Serum to treat disease – German
Cellularist – Existence of Phagocytic cells – Pioneer Elie Metchnikoff –
Observed WBC termed phagocyts ingesting microorganisms
– Phagocytic cells are active in the immunity of animals

16. Elvin Kabat (1930) identified this active component to be
Fraction in serum–  globulin (Immunoglobulin)
Antibodies in body fluids (Humor) – Humoral Immunity
Bruce Glick and Timothy Chang (1956)
B lymphocytes from the bursa of Fabricius (an outgrowth of the
cloaca in birds) were involved in humoral immunity
Francis A. P. Miller (1958)
the role of thymus-derived cells in cellular immunity
The controversy about the roles of humoral and cellular immunity was resolved
when the two systems were shown to be intertwined, and that both systems were
necessary for the immune response.

17. REFERENCES
10.1111/j.1469-0691.2012.03945.x
www.vbivaccines.com
https://en.wikipedia.org/wiki/Benjamin_Jesty
https://www.sciencehistory.org/historical-profile/paul-ehrlich
https://en.wikipedia.org/wiki/%C3%89lie_Metchnikoff
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1942006/
Kuby immunology –Judith A. Owen, Jenni Punt, Sharon A. Stranford;
with contributions by Patricia P. Jones. New York : W.H.
Freeman, 2013