Immunology and its history The term Immunology means In Latin – Immunis means ‘’exempt’’ In English – Immunity means state of protection from disease.

1. IMMUNOLOGY AND ITS HISTORY

2. Immune system
Immune system is evolved to protect the multicellular organisms from pathogens.
highly adaptable – it defends the body against invaders (diverse group)
generates
Immune system cells and molecules specifically recognise
eliminate the foreign invaders

3. Immune system gives
protection by two
activities
Recognition
Molecular patterns of common pathogen,
even chemical differences that distinguishes
one pathogen from another pathogen
Capacity to distinguish foreign invaders
from self components (Self – nonself
discrimination)
System can also recognise host cell that
are altered and that may lead to cancer
Response
Effector response – eliminates or
neutralize the invaders.
Memory response – prevent sus from
catching some disease a second time

4. Innate immunity Adaptive immunity
1. First line of defence mech.
Prevents most infections
Develops in response to infection
and adapts to recognise, eliminate
and then remember the invading
pathogen
Begins few days after the initial
infection
Distinguish self and pathogens Provides second line of defence that
eliminates pathogen that evade the
innate immune response
Not specialised to distinguish
small differences in foreign
molecules
Memory response – if the same
pathogen or closely related pathogen
infects the body, memory cells
effectively attack the invading
pathogen

5. HISTORICAL
PERSPECTIVE
The term Immunology means
In Latin – Immunis means ‘’exempt’’
In English – Immunity means state of protection from disease.
Thucydides (430BC).
The phenomenon of immunity was traced back to Thucydides (great
historian of Peloponnesian war). He described about plague in Athens that
those who recovered from plague could nurse the sick because they would not
contracted the disease second time. This laid the foundation for the
phenomenon of immunity.

6. Early vaccination studies
 Chinese (590 AD), Indians (ancient times) and Turks (15th centaury)
attempted to prevent smallpox a dreadful disease by using a technique
called ‘’Variolation’’ – dried crusts derived from smallpox pustules
were either inhaled into the nostrils or inserted into small cuts in the
skin.
 In 1718, Lady Mary Wortley Montagu (wife of British ambassador in
Constantinople) observed the positive effects of variolation and tried this
technique on her own children.
 Edinburg physician Francis home (1758) was familiar with the
procedure of variolation applied the same technique to inoculate against

7. EDWARD JENNER (1749-1823)(English
Physician)
 He was the first to initiate scientific approach to immunisation.
 In 1798, He identified that milkmaids who had contracted the mild disease cowpox
were subsequently immune to severe smallpox disease.
 He inoculated the fluid from cowpox pustules to an 8 year old boy to protect him from
smallpox. Then intentionally infected the child with smallpox, as he predicted, the
child did not contracted the disease smallpox.
 The process of vaccination was introduced by Jenner and according to WHO
Jennerian vaccination has eliminated small pox totally from the human population.

8. LOUIS PASTEUR (1822-1895) (French
Chemist)
 He is the Father of Immunology
 He demonstrated the principle of immunisation. He discovered attenuated
vaccine. He called the attenuated cultures as ‘’Vaccine’’ (Vacca means cow) to
honour Jenner's work with cowpox inoculation.
 Demonstrated the virulence (ability to cause disease) of bacteria.
 He worked on common diseases such as Pebrine (disease of silkworm),
Chicken cholera (disease of fowls), Anthrax (disease of cattle) and Rabies.

9. • He succeeded in growing the bacterium
(Pasteurella aviseptica) that cause fowl
cholera in culture.
• Injected the chickens with this cultured
bacterium developed fatal cholera and
died.
• After summer vacation, he injected the
chickens with old bacterial culture. The
chickens became ill but they recovered.
• Then he grew a fresh culture of bacterium
and injected into the recovered chickens,
now the chickens were completely
protected from the disease.
• He hypothesised and proved that aging
had weakened the virulence of the
pathogen such attenuated strain can be
administered to protect against disease.
Pasteur work on chicken cholera

10. Pasteur work on Anthrax vaccine
Bacillus anthracis was cultivated at
42˚C(high temperature)
Inoculated into sheep
Sheep did not develop the disease
anthrax
At normal temperature at 37˚C these
bacteria were highly pathogenic
He concluded that the pathogenic
bacteria lost their virulence on
cultivation at high temperature.
Attenuation - the process of weakening or reducing the virulence of pathogenic
organisms without losing the capacity to induce immunity.

11. Pasteur work on Rabies vaccine :
Rabies causing Rabdo virus is passed through
rabbit many times and vaccine was prepared.
He collected saliva from rabid dogs and injected into
normal healthy rabbits.
An extract was prepared from the infected rabbit
spinal cord.
Dried for several days at room temperature.
This extract contains attenuated viruses.
He proved that passing the microorganism into an
unnatural host also reduces its virulence.
Thus the microorganism lose their capacity to
produce serious disease but retained the capacity to
induce immunity.

12. Elie Metchnikoff (1845-1916) (Russian
Zoologist)
 He discovered the importance of cells in immunity and phagocytosis.
 While observing the transparent starfish larvae, he could see some motile cells.
 Later he observed some cells in Daphnia(water fleas) that ingest and destroy yeast
that are pathogenic to water fleas.
 He also suggested that inflammation might be a protective process rather than a
destructive process.
 In 1908, he shared his noble prize with Ehrlich for his contribution to immunity.
 He discovered cell mediated immunity. His work on phagocytic cells formed the basis
of cellular immunity.

13. George Nuttal (1888) & Pfeiffer (1894)
 George Nuttal found out that defibrinated blood had bactericidal effect, showing
the presence of a serum substance in blood which killed the bacteria.
 Pfeiffer reported that when cholera bacilli were injected into the peritoneal cavity
of immunized guinea pigs, the bacilli were destroyed by the peritoneal fluids and
immune serum showing the action of antibodies called Pfeiffer phenomenon.

14. Emil Von Behring (1854-1917) – German Bacteriologist
 The great support for ‘’Humoral theory’’ came from the studies of Behring.
 In 1890, he showed that it was possible to provide an animal with passive immunity
against tetanus or lockjaw by injecting into it the blood serum of another animal infected
with tetanus.
 He also showed that immunity could be obtained against diphtheria also by injecting
serum from an animal that had previously been injected with living cultures of the
Diphtheria bacilli.
 He proved that the anti-toxin activity resided in the cell free portion of the blood.

15. Almroth Wright (1861-1947) – British Bacteriologist
 By 1903, he discovered that neither the cellular theory nor the humoral theory was
wrong and that both were correct.
 Wright and Stewart Douglas formulated the theory of ‘’Opsonization’’. Wright termed
the serum substances, ‘’Opsonins’’.
 According to them opsonins and phagocytes are important in immunity to infectious
diseases and supplement one another in the destruction of pathogenic bacteria.
 Wright also had introduced antityphiod vaccine and had also done much work on the
preparation of other vaccines.

16. Emile Roux (1853-1933) – French Bacteriologist
 Along with Alexandre Yersin, he found the causative agent of diphtheria called Klebs-
Loeffler bacillus or Diphtheria bacilli. He studied its toxin and its properties, and began in
1891 to develop an effective serum to treat the disease.
 Emil Adolf von Behring (1854–1917) and Kitasato Shibasaburō (1852–1931) demonstrated
that antibodies against the diphtheria toxin could be produced in animals.
 Using this roux produced the anti-diphtheria serum in the pasture institute.

17. Charles Richet (1850-1935) – French Physiologist
 Richet was awarded the Nobel Prize in 1913 for his work on anaphylaxis.
 He coined the term anaphylaxis which means without or against protection.
 He worked along with Paul Portier on anaphylaxis (hypersensitive reactions of
the body to foreign proteins) which made them explain the conditions such as
hay fever, asthma, serum sickness and drug reactions.

18. Jules Bordet (1870-1961) – Belgian Physician & Bacteriologist
 In 1913, He won Nobel prize. He showed that the human blood normally contains a group of
heat labile substances which are strongly bactericidal when antibody is present. He named it as
“Alexin” which was later renamed as “complement” by Ehrlich.
 He also showed that the complement is absorbed and made inactive or fixed by the antigen-
antibody complexes. This complement-fixation becomes the basis for the laboratory identification
of the many disease causing organisms like Syphilis (),Typhoid (Samonella typhi), and
Tuberculosis (Mycobacterium tuberculosis).
 Bordet also studied the formation of anaphylactic poisons (produced at the time of complement
fixation) and coagulin.
 He and Octave Gengou in 1906 isolated the bacillus causing “whooping cough” which was
later known in the name of Bordet as Bordetella pertussis.

19. Paul Ehrlich (1854-1915) – German Scientist
 In 1908 he was awarded The Nobel Prize in Physiology or Medicine for his “work on immunity"
 Discovered Arsphenamine (Salvarsan), the first effective medicinal treatment for syphilis
 Immunity could be transferred from mother to an offspring.
 He formulated a theory of antibody formation in 1900 known as the “side chain hypothesis”
 He was the first to discover a special type of cells known as “mast cells” and he also observed that
these cells increased in conditions of chronic inflammation.
 He developed the concept of “horror autotoxicus” (organism's immune system could attack the own
tissue), in 1901.
 He popularized the concept of a “magic bullet“. This concept leads to the development of antibody-
drug conjugates (a monoclonal antibody linked to a cytotoxic biologically active drug that destructs the
targets), (e.g. cancer cell)
Mast cell

20. Robert Koch (1843 -1910 ) German Physician and Pathologist
 Koch, was awarded the Nobel prize in 1905 for his research in tuberculosis.
 He identified the causative agent of tuberculosis namely the tubercle bacilli
Mycobacterium tuberculosis in 1882. He also identified the protein derived from these
bacteria namely tuberculin.
 He identified the causative agent of cholera the Cholera bacillus and named it Cholera
Vibrio in 1883.
 He studied the life cycle of anthrax bacillus and its causative role in the disease.
 He introduced staining techniques and demonstrated the methods of obtaining bacteria in
pure culture using solid media.

21. Alexander Fleming(1881-1955) – British Bacteriologist
 Fleming shared the Nobel Prize in Physiology or Medicine in 1945 with Howard
Florey and Ernst Boris Chain.
 He discovered enzyme lysozyme (also known as muramidase or N-
acetylmuramide glycanhydrolase,) in 1923 and the antibiotic substance
benzylpenicillin (Penicillin G) from the mould Penicillium notatum in 1928

22. Widal Fernand (1862-1929) – French Physician and Bacteriologist
 Introduced the method of diagnosis of a disease by blood test.
 Devised the blood test known as Widal’s test for the diagnosis of typhoid fever.
 Prepared an antityphoid vaccine.
 With hematologist Georges Hayem (1841-1933), he described acquired haemolytic
anaemia, a disease that was historically referred to as "Hayem-Widal syndrome".

23. Karl Landsteiner (1863-1943) – Austrian Scientist
 Discovered ABO blood group system and got Nobel prize in 1901.
 He coined the term “Hapten” in 1921 to refer to small chemical groups that become
Immunogenic only when added to a carrier molecule.
 In 1940 Landsteiner and Weiner discovered the Rh antigen system common to human
beings and to the rhesus monkeys.
 In 1943 with Merill chase, He discovered that a class of allergy known as the “delayed
hypersensitivity” could be transferred from the allergic animal to a normal recipient with
lymphocytes

24. Burnet Macfarlane(1899-1985)
 Burnet in 1959 formulated the clonal selection theory of antibody formation.
 He shared the Nobel prize with Peter Medawar in 1960 for the discovery of “acquired
immunological tolerance”.
Issac and Lindenmann
 Issac and Lindenmann, discovered Interferons in 1957.
 The antigenic nonspecificity of interfons is an important difference between Interferons
and antibodies.
Rodney R. Porter(1917- 1985)
 Rodney R. Porter and Gerald M. Edelman received Nobel prize in 1972 for
their fundamental studies in the chemistry of Immunoglobulins.